PRIOR AUTHORIZATION CRITERIA

PRIOR AUTHORIZATION CRITERIA

SOUTH REGION PRIOR AUTHORIZATION CRITERIA AFINITOR (everolimus) Tablet: 2.5mg, 5mg, 7.5mg, 10mg STATUS Requires PA PA CRITERIA FOR APPROVAL Diagnosis of one of the following: -Advanced hormone receptor positive, human epidermal growth receptor 2 negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole -Advanced neuroendocrine tumors of pancreatic origin with unresectable, locally advanced, or metastatic disease -Advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib -Renal angiomyolipoma with tuberous sclerosis complex not requiring immediate surgery -Subependymal giant cell astrocytoma require therapeutic intervention but are not candidates for curative surgical resection AND Prescriber must be an oncologist. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred for medical necessity review. FDA INDICATIONS -Advanced hormone receptor positive, human epidermal growth receptor 2 negative breast cancer -Advanced neuroendocrine tumors of pancreatic origin -Advanced renal cell carcinoma -Renal angiomyolipoma with tuberous sclerosis complex -Subependymal giant cell astrocytoma DOSAGE AND ADMINISTRATION Recommended Dose in Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer, Advanced PNET, Advanced RCC, and Renal Angiomyolipoma with TSC: The recommended dose is 10 mg, to be taken once daily at the same time every day. Administer either consistently with food or consistently without food. Tablets should be swallowed whole with a glass of water. Do not break or crush tablets. Continue treatment until disease progression or unacceptable toxicity occurs Dose Modifications in Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer, Advanced PNET, Advanced RCC, and Renal Angiomyolipoma with TSC: Management of severe or intolerable adverse reactions may require temporary dose reduction and/or interruption of therapy. If dose reduction is required, the suggested dose is approximately 50% lower than the daily dose previously administered. Adverse Drug Reaction Non-infectious pneumonitis Severitya Grade 1 Asymptomatic, radiographic findings only Grade 2 Symptomatic, not interfering with ADLc Grade 3 Symptomatic, interfering with ADLc; O2 indicated Grade 4 Life-threatening, ventilatory support indicated Stomatitis Grade 1 Minimal symptoms, normal diet Grade 2 Symptomatic but can eat and swallow modified diet Grade 3 Symptomatic and unable to adequately aliment or hydrate orally AFINITOR Dose Adjustmentb and Management Recommendations No dose adjustment required. Initiate appropriate monitoring. Consider interruption of therapy, rule out infection and consider treatment with corticosteroids until symptoms improve to grade 1. Re-initiate AFINITOR at a lower dose. Discontinue treatment if failure to recover within 4 wks. Interrupt AFINITOR until symptoms resolve to grade 1. Rule out infection, and consider treatment with corticosteroids. Consider re-initiating AFINITOR at a lower dose. If toxicity recurs at grade 3, consider discontinuation. Discontinue AFINITOR, rule out infection, and consider treatment with corticosteroids. No dose adjustment required. Manage with non-alcoholic or salt water (0.9%) mouth wash several times a day. Temporary dose interruption until recovery to grade 1. Re-initiate AFINITOR at the same dose. If stomatitis recurs at grade 2, interrupt dose until recovery to grade 1. Re-initiate AFINITOR at a lower dose. Manage with topical analgesic mouth treatments (e.g. benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol or phenol) with or without topical corticosteroids (i.e. triamcinolone oral paste).d Temporary dose interruption until recovery to grade 1. Re-initiate AFINITOR at a lower dose. Manage with topical analgesic mouth treatments (i.e. benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol or phenol) with or without topical corticosteroids (i.e. triamcinolone oral paste).d

Recommended Dose in SEGA with TSC: The recommended starting dose is 4.5 mg/m2, once daily. The recommended starting dose for patients with severe hepatic impairment (Child-Pugh class C) or requiring moderate CYP3A4 and/or PgP inhibitors is 2.5 mg/m2, once daily. The recommended starting dose for patients requiring a concomitant strong CYP3A4 inducer is 9 mg/m2. Use therapeutic drug monitoring to guide subsequent dosing. Adjust dose at two week intervals as needed to achieve and maintain trough concentrations of 5 to 15 ng/ml. Continue treatment until disease progression or unacceptable toxicity occurs. The optimal Other nonhematologic toxicities (excluding metabolic events) Metabolic events (e.g. hyperglycemia, dyslipidemia) Grade 4 Symptoms associated with life-threatening consequences Grade 1 Discontinue AFINITOR and treat with appropriate medical therapy. If toxicity is tolerable, no dose adjustment required. Initiate appropriate medical therapy and monitor. Grade 2 If toxicity is tolerable, no dose adjustment required. Initiate appropriate medical therapy and monitor. If toxicity becomes intolerable, temporary dose interruption until recovery to grade 1. Re-initiate AFINITOR at the same dose. If toxicity recurs at grade 2, interrupt AFINITOR until recovery to grade 1. Re-initiate AFINITOR at a lower dose. Grade 3 Temporary dose interruption until recovery to grade 1. Initiate appropriate medical therapy and monitor. Consider re-initiating AFINITOR at a lower dose. If toxicity recurs at grade 3, consider discontinuation. Grade 4 Discontinue AFINITOR and treat with appropriate medical therapy. Grade 1 No dose adjustment required. Initiate appropriate medical therapy and monitor. Grade 2 No dose adjustment required. Manage with appropriate medical therapy and monitor. Grade 3 Temporary dose interruption. Re-initiate Afinitor at a lower dose. Manage with appropriate medical therapy and monitor. Grade 4 Discontinue AFINITOR and treat with appropriate medical therapy. a Severity grade description: 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms. b If dose reduction is required, the suggested dose is approximately 50% lower than the dose previously administered. c Activities of daily living (ADL) d Avoid using agents containing alcohol, hydrogen peroxide, iodine, and thyme derivatives in management of stomatitis as they may worsen mouth ulcers. Hepatic Impairment: Mild hepatic impairment (Child-Pugh class A) The recommended dose is 7.5 mg daily; the dose may be decreased to 5 mg if not well tolerated. Moderate hepatic impairment (Child-Pugh class B) The recommended dose is 5 mg daily; the dose may be decreased to 2.5 mg if not well tolerated. Severe hepatic impairment (Child-Pugh class C) If the desired benefit outweighs the risk, a dose of 2.5 mg daily may be used but must not be exceeded. CYP3A4 and/or P-glycoprotein (PgP) Inhibitors: Avoid the use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole). Use caution when co-administered with moderate CYP3A4 and/or PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). If patients require co-administration of a moderate CYP3A4 and/or PgP inhibitor, reduce the AFINITOR dose to 2.5 mg daily. The reduced dose of AFINITOR is predicted to adjust the area under the curve (AUC) to the range observed without inhibitors. An AFINITOR dose increase from 2.5 mg to 5 mg may be considered based on patient tolerance. If the moderate inhibitor is discontinued, a washout period of approximately 2 to 3 days should be allowed before the AFINITOR dose is increased. If the moderate inhibitor is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the moderate CYP3A4 and/or PgP inhibitor. Grapefruit, grapefruit juice, and other foods that are known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment. Strong CYP3A4 Inducers: Avoid the use of concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). If patients require co-administration of a strong CYP3A4 inducer, consider increasing the AFINITOR dose from 10 mg daily up to 20 mg daily, using 5 mg increments. This dose of AFINITOR is predicted, based on pharmacokinetic data, to adjust the AUC to the range observed without inducers. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer. St. John s Wort (Hypericum perforatum) may decrease everolimus exposure unpredictably and should be avoided.

duration of therapy is unknown. Dose Modifications in SEGA with TSC: Reduce dose or withhold for severe or intolerable adverse reactions. Reduce the dose by approximately 50%. If dose reduction is required for patients receiving the lowest available strength, administer every other day. Hepatic Impairment: Reduce the starting by approximately 50% in patients with SEGA who have severe hepatic impairment (Child-Pugh class C). Adjustment to the starting dose for patients with SEGA who have mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment may not be needed. Subsequent dosing should be based on therapeutic drug monitoring. Assess everolimus trough concentrations approximately two weeks after commencing treatment, a change in dose, or any change in hepatic function. CYP3A4 and/or P-glycoprotein (PgP) Inhibitors: Avoid the use of concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole). For patients who require treatment with moderate CYP3A4 and/or PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem): Reduce dose by approximately 50%. Administer every other day if dose reduction is required for patients receiving the lowest available strength.assess everolimus trough concentrations approximately two weeks after dose reduction. Resume the dose that was used prior to initiating the CYP3A4 and/or PgP inhibitor 2 to 3 days after discontinuation of a moderate inhibitor. Assess the everolimus trough concentration approximately two weeks later. Do not ingest foods or nutritional supplements (e.g., grapefruit, grapefruit juice) that are known to inhibit cytochrome P450 or PgP activity. Strong CYP3A4 Inducers: Avoid the use of concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) if alternative therapy is available. For patients who require treatment with a strong CYP3A4 inducer: Double the dose. Assess the everolimus trough concentration two weeks after doubling the dose and adjust the dose if necessary to maintain a trough concentration of 5 to 15 ng/ml. Return the dose to that used prior to initiating the strong CYP3A4 inducer if the strong inducer is discontinued, and assess the everolimus trough concentrations approximately two weeks later. Do not ingest foods or nutritional supplements (e.g., St. John s Wort (Hypericum perforatum)) that are known to induce cytochrome P450 activity. REFERENCES 1. Facts and Comparisons, St. Louis, 2013 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Afinitor. Prescribing Information. Novartis Pharmaceuticals Corporation. August 2012. Revision/Review Date: 7/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE 5- HYDROXYTRYPTAMINE-3 (5HT 3 ) SEROTONIN RECEPTOR ANTAGONISTS FORMULARY STATUS: Generic Ondansetron or Granisetron Preferred Aloxi palonosetron hydrochloride: 0.25 mg in 5 ml, is supplied as a single-use vials ready for intravenous injection Anzemet dolasetron mesylate: 20mg/ml supplied as 12.5mg/0.625ml single-use vial, 12.5mg/0.625ml fill in single-use 2ml cartridge, 100mg/5ml single-use vial, 500mg/25ml multi-dose vial Kytril granisetron hydrochloride: 1 mg/1 ml, is supplied in 1 ml single-use vials and 4 ml multi-use vials and 0.1 mg/1 ml, is supplied in 1 ml single-use vials Zofran ondansetron: 2 mg/ml is supplied as follows: 2 ml single-dose vials and 20 ml multidose vials (singles) Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, Drug Package Insert) as defined in the Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), National Cancer Institute {NCI} (a Division of the U.S. National Institutes of Health) and the Multinational Association of Supportive Care in Cancer (MASCC) standard of care guidelines for antiemetic therapy. Patients receiving an antineoplastic agent classified as Level 4 or greater per the Hesketh classification (see appendix 1 ) can receive Aloxi (palonosetron hydrochloride) as a first line antiemetic agent. For all other patients, if the medication request is for any other 5-hydroxytryptamine-3 (5HT 3 ) serotonin receptor antagonist other than generic Ondansetron or generic Granisetron, the patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) treatment failure after receiving an adequate trial of generic Ondansetron or generic Granisetron and/or has another documented medical reason ( intolerance, hypersensitivity, contraindication, etc) for not utilizing these medications to treat their medical condition. Prescribed dosing of the 5HT 3 serotonin receptor antagonist is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, NCI or MASCC standard of care guidelines. The medication is recommended and prescribed by a specialist in the field to treat the patient s respective medical condition If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, NCI or MASCC standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN, ASCO, NCI or MASCC standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, NCI or MASCC standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA Approved Indications, Dosing and Administration: Palonosetron (Aloxi ) Highly or moderately emetogenic chemotherapy-induced [acute or delayed] nausea and vomiting prophylaxis:

18 y/o and older: single dose of 0.25 mg administered IV over 30 seconds given approximately 30 minutes before the start of chemotherapy. No safety or efficacy established for repeat doses, therefore, administration of an additional dose within a 7-day period is not recommended. Postoperative Nausea and Vomiting 18 y/o and older: single dose of 0.25 mg administered IV over 10 seconds given immediately before the induction of anesthesia. Dolasetron (Anzemet ) Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis in adults or children: For patients 2-16 y/o:1.8 mg/kg IV given over a period of up to 15 minutes, beginning approximately 30 minutes before administration of emetogenic chemotherapy drug. (Maximum pediatric dose is 100 mg). For patients 17 y/o and older: 1.8mg/kg given as a single dose approximately 30 minutes before chemotherapy. Alternatively, for most patients, a fixed dose of 100mg can be administered over 30 seconds. Post-Operative nausea and vomiting: 17 y/o and older (prophylaxis): 12.5 mg IV as a single dose approximately 15 minutes before cessation of anesthesia. 17 y/o and older (treatment): 12.5 mg IV as a single dose as soon as nausea and/or vomiting presents. 2-16 y/o (prophylaxis and treatment): 0.35 mg/kg as a single dose approximately 15 minutes before cessation of anesthesia or as soon as nausea and/or vomiting develops to a maximum dose of 12.5 mg per dose. Granisetron (Kytril ) Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis in adults or children: 10 mcg/kg IV administered within 30 minutes before initiation of emetogenic chemotherapy. The dose may be administered undiluted over 30 seconds, or diluted in 5% dextrose or NSS and infused over 5 minutes. Pediatric patients under 2 years of age have not been studied. Post-Operative nausea and vomiting: 4 y/o and older (prophylaxis): single IV dose of 1 mg is given undiluted over 30 seconds before induction of anesthesia or immediately before reversal of anesthesia. 4 y/o and older (treatment): 1 mg undiluted IV is given over 30 seconds. Ondansetron (Zofran ) Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis: {several regimens exist} 18 y/o and older single-dose of 32mg given as a 15 minute infusion IV 30 minutes before administration of single day chemotherapy agent. Do not repeat. This dosing is typically reserved for highly emetogenic chemotherapy 0.15mg/kg as 15 minute infusion begin 30 minutes before administration of chemotherapy and subsequent doses given at 4 and 8 hours after first dose. 8 mg IV over 15 minutes begin 30 minutes prior to chemotherapy followed immediately by a continuous infusion of 1mg/hr for up to 24 hrs. 6 mos to 18 y/o: 0.15mg/kg as 15 minute infusion begin 30 minutes before administration of chemotherapy and subsequent doses given at 4 and 8 hours after first dose. 3-5mg/m2 given over 15 minutes begin immediately prior to chemotherapy followed after chemotherapy by oral ondansetron 4 mg Q8hrs for up to 5 days. Post-Operative nausea and vomiting: 12 y/o and older (prophylaxis): single IV dose of 4 mg preferably over 2-5 minutes beginning immediately prior to induction of anesthesia OR 4mg as a single undiluted IM injection given immediately prior to induction of anesthesia. 12 y/o and older (treatment): if patient experiences nausea and/or vomiting shortly after surgery can give single IV dose of 4 mg.

1month -12y/o (prophylaxis and treatment): single IV dose of 0.1 mg/kg for patient weight of 40kg or less OR if weight is between 40-80 kg give single IV dose of 4mg IV. Administer over 2-5 minutes immediately prior to or following anesthesia induction or shortly after surgery if nausea and/or vomiting occurs. Per the manufacturer of ondansetron, if the patient does not achieve adequate control of postoperative nausea and vomiting with a single 4 mg IV dose given prior to induction of anesthesia they will not benefit from a 2 nd 4mg dose given postop. References: 1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Antiemesis. Version 3.2009. 2. American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update 2006. Journal of Clinical Oncology.2006; 24(18):2932-2947. Erratum pages 5341-5342. 3. Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer (MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at www.mascc.org 4. US National Institutes of Health. National Cancer Institute. Nausea and vomiting PDQ. Health Professional Version. Treatment of acute/delayed emesis. Available at www.cancer.gov/cancertopics/pdq/supportivecare/nausea/healthprofessional. Last modified 10/19/2006. 5. Roila F. Warr D. Clark-Snow RA. Et al. Delayed emesis: moderately emetogenic chemotherapy. Supportive Cancer Care. 2005;13:104-108. 6. Prescribing information Kyril. Roche Pharmaceuticals. 11/2005. 7. Prescribing information Anzemet Sanofi-aventis. 10/2009. 8. Prescribing information Aloxi. Helsinn. 02/2008. 9. Prescribing information Zofran. GlaxoSmithKline. 10/2009. 10. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for Classifying the Acute Emetogenicity of Cancer Chemotherapy. Journal of Clinical Oncology.1997;15(1): 103-09. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. APPENDIX 1 Level Frequency of Emesis (%) 5 >90 4 60-90 3 30-60 2 10-30 1 < 10 Emetogenic Potential of Single Chemotherapy Agents Agent Carmustine > 250mg/m 2, Cisplatin > 50mg/m 2, Cyclophosphamide > 1,500 mg/m2, Dacarbazine, Mechlorethamine, Streptozocin Carboplatin, Carmustine < 250mg/m 2, Cisplatin <50mg/m 2, Cyclophosphamide > 750mg/m 2 < 1,500 mg/m 2, Cytarabine > 1g/ m 2, Doxorubicin > 60 mg/m 2, Methotrexate > 1,000 mg/m 2, Procarbazine (oral) Cyclophosphamide < 750mg/m 2, Cyclophosphamide (oral), Doxorubicin 20-60 mg/m 2, Epirubicin < 90 mg/m 2, Hexamethylmelmine (oral), Idarubicin, Methotrexate 250-1,000 g/ m 2, Mitoxantrone < 15 mg/m 2 Docetaxel, Etoposide, 5-FU <1,000 mg/ m 2, Gemcitabine, Methotrexate > 50 < 250 mg/ m 2, Mitomycin, Paclitaxel Bleomycin, Busulfan, Chlorambucil (oral), 2-Chlorodeoxyadenosine, Fludarabine, Hydroxyurea, Methotrexate < 50 mg/ m 2, L-phenylalanine mustard (oral), Thioguanine (oral), Vinblastine, Vincristine, Vinorelbine Hesketh PJ, Kris MG, Grunberg SM, et al.. Proposal for Classifying the Acute Emetogenicity of Cancer Chemotherapy. Journal of Clinical Oncology.199715(1): 103-09 APPENDIX 2 : EMETIC RISK GROUPS High Risk in nearly all patients (> 90%) Moderate Risk in 30% to 90% of patients Low Risk in 10% to 30% of patients Minimal Fewer than 10% at risk Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer (MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at www.mascc.org Emetic Risk of Intravenously Administered Antineoplastic Agents Emetic Risk (incidence of emesis Agent

without antiemetics) High (>90%) Moderate (30-90%) Low (10-30%) Minimal (<10%) Cisplatin 50 mg/m2, Mechlorethamine, Streptozocin, Cyclophosphamide 1500mg/m2, Carmustine, Dacarbazine, Dactinomycin, Altretamine, AC combination defined as either Doxorubicin or Epirubicin with Cyclophosphamide Cisplantin < 50mg/m2, Oxaliplatin, Cytarabine >1g/m2, Carboplatin, Ifosfamide, Cyclophosphamide <1500mg/m2, Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Irinotecan, Aldesleukin >12-15 milllion units/m2, Amifostine >300 mg/m2, Arsenic Trioxide, Azacitidine, Bisulfan >4mg/day, Dactinomycin, Lomustine, Melphalan >50mg/m2, Methotrexate 250->1000 mg/m2, Amifostine <300 mg/m2, Bexarotene,Paclitaxel, Paclitaxel-albumin, Docetaxel, Mitoxantrone, Topotecan, Etoposide, Pemetrexed, Methotrexate >50mg/m2<250mg/m2, Mitomycin, Doxorubicin Liposomal, Gemcitabine, Cytarabine 1000mg/m2, 5-Fluorouracil, Bortezomib, Cetuximab, Trastuzumab Alemtuzumab, Alpha Interferon, Asparaginase, Bevacizumab, Bleomycin, Bortezomib, Busulfan, 2-Chlorodeoxyadenosine (Cladribine), Decitabine, Denileukin difititox, Dexrazoxane, Fludarabine, Gemtuzumab ozogamicin, Methotrexate 50mg/m2, Nelarabine, Pentostatin, Rituximab, Trastuzumab, Vinblastine, Vincristine, Vinorelbine American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update 2006. Journal of Clinical Oncology.2006;24(18):2932-2947. Erratum pages 5341-5342.; National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2007. Emetic Risk of Orally Administered Antineoplastic Agents Agent Emetic Risk (incidence of emesis without antiemetics) High (>90%) Moderate (30-90%) Low (10-30%) Minimal (<10%) Hexamethylmelamine, Procarbazine Cyclophosphamide, Etoposide, Temozolomide, Vinorelbine, Imatinib Capecitabine, Fludarabine Chlorambucil, Hydroxyurea, L-Phenylalanine mustard, 6-Thioguanine, Methotrexate, Gefitinib, Dasatinib, Erlotinib, Lenalidomide, Melphalan, Sorafenib, Sunitinub, Thalidomide, Thioguanine, Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer (MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at www.mascc.org Emetic Risk with Radiation Therapy Emetic Risk (incidence of emesis Agent without antiemetics) High (>90%) Total Body Irradiation Moderate (30-90%) Upper Abdomen Low (10-30%) Lower thorax region, Pelvis, Cranium (radiosurgery), Craniospinal Minimal (<10%) Head and Neck, Extremities, Cranium, Breast Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer (MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at www.mascc.org; American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update 2006. Journal of Clinical Oncology.2006;24(18):2932-2947. Erratum pages 5341-5342

TRUE HEALTH PRIOR AUTHORIZATION PROTOCOL FOR ALPHA-1 PROTEINASE INHIBITORS (HUMAN) Alpha 1 -Proteinase Inhibitor (human) (Prolastin ) approximately 500 mg vial with 20 ml diluent, approximately 1000 mg vial with 40 ml. Alpha 1 -Proteinase Inhibitor (human) (Aralast ) approximately 500 mg vial (not less than 400 mg) with 25 ml diluent, 1000 mg vial (not less than 800 mg) with 50 ml diluent. Alpha 1 -Proteinase Inhibitor (human) (Zemaira ) approximately 1000 mg with 20 ml diluent. PA CRITERIA FOR INITIAL APPROVAL: The member is an adult ( 18 y/o) and has a documented diagnosis of a congenital deficiency of alpha-1 antitrypsin (ATT) [serum level < 11μM or 80mg/dl]. Documentation was submitted indicating the member has undergone genetic testing for ATT deficiency by isoelectric focusing in polyacrylamide gel and is classified as phenotype PiZZ, PiZ(null) or Pi(null)(null) variant of alpha-1-antitrypsin deficiency [NOTE: phenotypes PiMZ or PiMS are not candidates for treatment with Alpha 1 -Proteinase Inhibitors]. Documentation was submitted indicating the member does not have selective IgA deficiency (IgA level < 15 mg/dl) with known antibodies against IgA. The Alpha 1 -Proteinase Inhibitor (human) is being prescribed by a pulmonologist. The Alpha 1 -Proteinase Inhibitor (human) is being prescribed at an FDA approved dosage. If the medication request is for an Alpha 1 -Proteinase Inhibitor (human) product other than Prolastin, the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, treatment failure, etc) for not using Prolastin to treat their medical condition. If all of the above conditions are met, the request will be approved up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION: The Alpha 1 -Proteinase Inhibitor (human) is being prescribed by a pulmonologist. Documentation was submitted indicating the member has clinically benefited from therapy (i.e. improved lung function tests {pulmonary function tests}), alpha-1 antitrypsin serum level maintained above 80 mg/dl, improved quality of life). The Alpha 1 -Proteinase Inhibitor (human) is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Alpha 1 Proteinase Inhibitors (HUMAN) are indicated for chronic augmentation therapy in patients having congenital deficiency of alpha 1 PI (alpha 1 antitrypsin deficiency) and clinical evidence of emphysema. DOSAGE AND ADMINISTRATION: Alpha 1 Proteinase Inhibitors (HUMAN) are dosed at 60mg/kg body weight and are administered once weekly via IV infusion at a rate of approximately 0.08ml/kg/min. The infusion rate may be adjusted based on the patient s tolerability (i.e. tolerance of prior dosing schedule). REFERENCES: 1. Alpha-1 Antitrypsin Deficiency Task Force of the Clinical Problems Assembly. American Thoracic Society/European Respiratory Society Statement: Standard for the diagnosis and management of

individuals with alpha-1 antitrypsin deficiency. Statement developed jointly by an ATS/ERS task force. American Journal of Respiratory & Critical Care Medicine. 2003;168:818-900. 2. Teckman JH. Lindblad D. Alpha-1 antitrypsin deficiency: diagnosis, pathophysiology, and management. Current Gastroenterology Reports. 2006;8:14-20. 3. Sandhaus RA. Alpha-1 antitrypsin deficiency: a history through the medical literature. A compendium of classic papers. Cambridge Medical Publications. 2006. 4. Middleton ET. Morice AH. Breath carbon monoxide as an indication of smoking habit. Chest. 2000;117(3):758-763. 5. Prolastin Prescribing Information. Talecris Biotherapeutics, Inc. June 2008. 6. Zemaira Prescribing Information. ZLB Behring LLC. January 2007. 7. Aralast Prescribing Information. Baxter Healthcare Corporation. May 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA AMPYRA TM (dalfampridine): 10 mg tablets, extended-release Formulary Status: Non-Formulary requiring prior authorization PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): Documentation submitted indicates that the member is an adult ( 18 y/o) and has a clinical diagnosis of multiple sclerosis. Baseline diagnostic and/or clinical documentation was submitted (e.g. 12-item MS walking scale, timed 25-foot walk, Ashworth score for spasticity, lower extremity manual muscle test, quality of life etc.) that documents member s baseline walking dysfunction For patients who have a clinical diagnosis of relapsing remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS) then that patient has documented (consistent with pharmacy claims data OR for new members to the health plan consistent with medical chart history) concurrent use of one of the following immunomodulating therapies: Avonex (Interferon beta-1b), Betaseron (Interferon beta-1b), Copaxone (glatiramer acetate), Extavia (Interferon beta- 1b), Rebif (Interferon beta-1a), or has a some other documented medical reason (intolerance, hypersensitivity, etc) for not utilizing one of these therapies to manage their medical condition. AMPYRA is being prescribed or recommend by a neurologist at an FDA-approved dosage If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION FOR USE IN MS: Diagnostic or clinical documentation was submitted (e.g. 12-item MS walking scale, timed 25-foot walk, Ashworth score for spasticity, lower extremity manual muscle test, quality of life etc.) indicating that member has demonstrated improvement in walking while receiving AMPYRA therapy AMPYRA is being prescribed or recommend by a neurologist at an FDA-approved dosage If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: The medication is recommended and prescribed by a specialist in the member s disease state The medication is prescribed for a medically accepted use at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, AHFS drug information) as defined by the Social Security Act Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard of care guidelines and/or has a documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s) If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: The medication is recommended or prescribed by a specialist in the member s disease state Diagnostic and/or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence) that indicates the member has significantly clinically benefited from receiving AMPYRA therapy

The medication is prescribed for a medically accepted use at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points, AHFS drug information) as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. FDA INDICATIONS: Multiple Sclerosis: AMPYRA (dalfampridine) is a potassium channel blocker indicated to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed. The use of AMPYRA is contraindicated in the following conditions: history of seizure, moderate or severe renal impairment (CrCl 50 ml/minute). DOSAGE AND ADMINISTRATION: The maximum recommended dose of AMPYRA is one 10 mg tablet twice daily, taken with or without food, and should not be exceeded. Doses should be taken approximately 12 hours apart. Patients should not take double or extra doses if a dose is missed. No additional benefit was demonstrated at doses greater than 10 mg twice daily and adverse reactions and discontinuations because of adverse reactions were more frequent at higher doses. REFERENCES: 1. Fischer JS, Jak AJ, Kniker JE, Rudick RA et al. Multiple sclerosis functional composite administration and scoring manual. National Multiple Sclerosis Society, Oct 2001. 2. Hobart JC, Riazi A, Lamping DL, Fitzpatrick R. Measuring the impact of MS on walking ability. Neurology 2003;60:31-36. 3. Katz RT. Spasticity. In: O'Young B, Young MA, Stiens SA. PM&R Secrets. Ed. Sara J Cuccurullo, MD. Philadelphia; Hanley & Belfus, 1997. 4. Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8. 5. Kachuck NJ. Sustained release oral fampridine in the treatment of multiple sclerosis. Expert Opin Pharmacother. 2009 Aug;10(12):2025-35. 6. Thompson A, Polman C. Improving function: a new treatment era for multiple sclerosis? Lancet. 2009 Feb 28;373(9665):697-8. 7. Bever CT, Judge SI. Sustained-release fampridine for multiple sclerosis. Expert Opin Investig Drugs. 2009 Jul;18(7):1013-24. 8. Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, Cohen R, Marinucci LN, Blight AR; Fampridine MS-F202 Study Group. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology. 2008 Oct 7;71(15):1134-41. 9. Kryscio RJ. Fampridine for MS responders: clinically relevant or hypothesis generating? Neurology. 2008 Oct 7;71(15):1130-1. Revision/Review Date: 02/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

APPENDIX 1: The 12-Item Multiple Sclerosis Walking Scale (MSWS-12) In the past two weeks, how much has your MS Not at all A little Moderately Quite a bit Extremely 1. Limited your ability to walk? 1 2 3 4 5 2. Limited your ability to run? 1 2 3 4 5 3. Limited your ability to climb up and 1 2 3 4 5 down stairs? 4. Made standing when doing things 1 2 3 4 5 difficult? 5. Limited your balance when standing or 1 2 3 4 5 walking? 6. Limited how far you are able to walk? 1 2 3 4 5 7. Increased the effort needed for you to 1 2 3 4 5 walk? 8. Made it necessary for you to use 1 2 3 4 5 support when walking indoors (e.g. holding onto furniture, using a stick, etc.)? 9. Made it necessary for you to use 1 2 3 4 5 support when walking outdoors (e.g. using a stick, a frame, etc.)? 10. Slowed down your walking? 1 2 3 4 5 11. Affected how smoothly you walk? 1 2 3 4 5 12. Made you concentrate on your 1 2 3 4 5 walking? Adapted from: Hobart JC, Riazi A, Lamping DL, Fitzpatrick R. Measuring the impact of MS on walking ability. Neurology 2003;60:31-36. APPENDIX 2: The Timed 25-Foot Walk (T25FW) DESCRIPTION The Timed 25-Foot Walk (T25FW) is a quantitative measure of lower extremity function. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. In clinical trials, it is recommended that the treating neurologist select the appropriate assistive device for each patient. TIME LIMIT PER TRIAL 3 minutes (180 seconds) per trial. ADMINISTRATION Trial 1 The subject should be directed to one end of a clearly marked 25-foot course (clearly defined on the floor or on the wall) and instructed to stand just behind the starting line. Point out where the 25-foot course ends, then instruct the patient as follows: I d like you to walk 25 feet as quickly as possible, but safely. Do not slow down until after you ve passed the finish line. Ready? Go.

Begin timing when the lead foot is lifted and crosses the starting line. Stop timing when the lead foot crosses the finish line. Trial 2 After completing the first timed walk, position the patient just behind the line where s/he is now standing, repeat the same instructions, and have the patient complete the walk again. Assistive Devices In clinical trials and other serial studies, the goal is to use the same assistive device at each study visit. The treating neurologist should select an assistive device at the beginning of the study for each patient who needs one, keeping in mind that the patient may deteriorate modestly over the course of a trial. In general, patients should use their customary assistive device(s), NOT the least assistance possible to complete the test. For patients with significant gait impairment, the treating neurologist should have the patient use a rolling walker even if this is not the patient s customary device. In general, nonwheeled walkers should not be used. If a patient does use an assistive device, this should be noted on the Record Form. Completing the Record Form Record only the times for the two successfully completed trials of the Timed 25-Foot Walk. If the patient could not complete one or both of the trials of the Timed 25-Foot Walk, record this in the appropriate section of the Record Form. For example, if the patient s disease has progressed and/or physical limitations prohibit him or her from completing the trial, you should indicate Unable to complete trial due to physical limitations, and record any specifics that you can observe (i.e., patient in a wheelchair now and unable to walk, etc.). If the patient did not complete a trial for any other reason, specify this as well (e.g., patient fell and was too fatigued to complete another trial; patient refused to complete trial). Adapted from: Fischer JS, Jak AJ, Kniker JE, Rudick RA et al. Mutiple sclerosis functional composite administration and scoring manual. National Multiple Sclerosis Society, Oct 2001. APPENDIX 3: The Modified Ashworth Scale (Bohannon & Smith, 1987) SCORE DESCRIPTION 0 No increase in muscle tone 1 Slight increase in muscle tone, manifested by a catch and release or minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM 2 More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3 Considerable increase in muscle tone, passive movement difficult 4 Affected part(s) rigid in flexion or extension Adapted from Katz RT. Spasticity. In: O'Young B, Young MA, Stiens SA. PM&R Secrets. Ed. Sara J Cuccurullo, MD. Philadelphia; Hanley & Belfus, 1997.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ANGIOTENSIN II RECEPTOR BLOCKER AND RENIN INHIBITOR MEDICATIONS FORMULARY STATUS: Formulary, Pays at Point-of-Sale (First Line) Cozaar (Losartan) Tablets: 25 mg, 50 mg, 100 mg Hyzaar (Losartan/Hydrochlorothiazide) Tablets: 50mg/12.5mg, 100mg/12.5mg, 100mg/25mg FORMULARY STATUS: Formulary, Requires Step Therapy (Second Line) Amturnide (Aliskiren/Amlodipine/Hydrochlorothiazide) Tablets: 150mg/5mg/12.5mg, 300mg/5mg/12.5mg, 300mg/5mg/25mg, 300mg/10mg/12.5mg, 300mg/10mg/25mg Diovan (Valsartan) Tablets: 40 mg, 80mg, 160mg, 320mg Diovan-HCT (Valsartan/Hydrochlorothiazide) Tablets: 80mg/12.5mg, 160mg/12.5mg, 160mg/25mg,320mg/12.5mg, 320mg/25mg Exforge (Amlodipine Besylate/Valsartan) Tablets: 5mg/160mg, 5mg/320mg, 10mg/160mg, 10mg/320mg Exforge HCT (Amlodipine/Valsartan/Hydrochlorothiazide) Tablets: 5mg/160mg/12.5mg, 10mg/160mg/12.5mg, 5mg/160mg/25mg, 10mg/320mg/25mg Tekturna (Aliskiren hemifumarate) Tablets: 150mg, 300mg Tekturna HCT (Aliskiren/Hydrochlorothiazide) Tablets: 150mg/12.5mg, 300mg/12.5mg Valturna (Aliskiren/Valsartan) Tablets: 150mg/160mg, 300mg/320mg Tekamlo (Aliskiren/Amlodipine) Tablets: 150mg/5mg, 150mg/10mg, 300mg/5mg, 300mg/10mg NOTE: Patient must meet criteria #1 for approval of initial PA request. FORMULARY STATUS: Non-Formulary, Requires Prior Authorization (Third Line) Atacand (Candesartan Cilexetil) Tablets: 4mg, 8mg, 16mg, 32mg Avapro (Irbesartan) Tablets: 75mg, 150mg, 300mg Benicar (Olmesartan Medoxomil) Tablets: 5mg, 20mg, 40mg Micardis (Telmisartan) Tablets: 20mg, 40mg, 80mg Teveten (Eprosartan Mesylate) Tablets: 400mg, 600mg Atacand HCT(Candesartan Cilexetil/ Hydrochlorothiazide) Tablets: 8mg/12.5mg, 32mg/12.5mg, 32mg/25mg Avalide (Irbesartan/Hydrochlorothiazide) Tablets: 150mg/12.5mg, 300mg/12.5mg, 300mg/25mg Azor (Amlodipine Besylate/Olmesartan Medoxomil) Tablets: 5mg/20mg, 5mg/40mg, 10mg/20mg, 10mg/40mg Benicar HCT (Olmesartan Medoxomil/ Hydrochlorothiazide) Tablets: 20mg/12.5mg, 40mg/12.5mg, 40mg/25mg Micardis-HCT (Telmisartan/Hydrochlorothiazide) Tablets: 40mg/12.5mg, 80mg/12.5mg, 80mg/25mg Teveten-HCT (Eprosartan Mesylate/ Hydrochlorothiazide) Tablets: 600mg/12.5mg, 600mg/25mg Tribenzor (Olmesartan Medoxomil/Amlodipine/Hydrochlorothiazide) Tablets: 20mg/5mg/12.5mg, 40mg/5mg/12.5mg, 40mg/5mg/25mg,40mg/10mg/12.5mg, 40mg/10mg/25mg Twynsta (Telmisartan/Amlodipine) Tablets: 40mg/5mg, 40mg/10mg, 80mg/5mg, 80mg/10mg NOTE: Patient must meet criteria #1 & #2 for approval of initial PA request. PA CRITERIA FOR APPROVAL 1. Documented trial and failure or intolerance with a first line agent for at least 15 days of therapy within the previous 60 days. 2. Documented trial and failure or intolerance with a second line agent for at least 15 days of therapy within the previous 60 days. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. REFERENCES 1. Amturnide. Prescribing Information. Novartis Pharmaceuticals Corp. December 2010. 2. Atacand. Prescribing Information. AstraZeneca Pharmaceuticals, Inc. October 2009. 3. Avapro. Prescribing Information. Bristol-Myers Squibb Sanofi-Synthelabo Partnership. April 2007. 4. Benicar. Prescribing Information. Daiichi Sankyo, Inc. February 2010. 5. Cozaar. Prescribing Information. Merck & Co. June 2010. 6. Diovan. Prescribing Information. Novartis Pharmaceuticals Corp. June 2010. 7. Micardis. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. November 2009.

8. Teveten. Prescribing Information. Abbott Laboratories. June 2010. 9. Atacand-HCT. Prescribing Information. AstraZeneca Pharmaceuticals. May 2008. 10. Avalide. Prescribing Information. Bristol-Myers Squibb Sanofi-Synthelabo Partnership. September 2010. 11. Azor. Prescribing Information. Daiichi Sankyo, Inc. May 2009. 12. Benicar HCT. Prescribing Information. Daiichi Sankyo, Inc. July 2007. 13. Diovan-HCT. Prescribing Information. Novartis Pharmaceuticals Corp. April 2010. 14. Exforge. Prescribing Information. Novartis Pharmaceuticals Corp. February 2009. 15. Exforge HCT. Prescribing Information. Novartis Pharmaceuticals Corp. August 2009. 16. Hyzaar. Prescribing Information. Merck & Co. June 2010. 17. Micardis-HCT. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. November 2009. 18. Teveten-HCT. Prescribing Information. Abbott Laboratories. June 2010. 19. Tribenzor. Prescribing Information. Daiichi Sankyo Laboratories. July 2010. 20. Twynsta. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. August 2010. 21. Micromedex. Available from http://thomsonhc.com. Accessed May 2011. 22. Drugs Facts and Comparisons. Available from http://online.factsandcomparisons.com. Accessed May 2011. 23. Lexi-Comp. Available from: http://online.lexi.com.db.usip.edu/crlsql/servlet/crlonline. Accessed May 2011. 24. Tekturna. Prescribing Information. Novartis Pharmaceuticals. May 2011. 25. Tekturna HCT. Prescribing Information. Novartis Pharmaceuticals. February 2011. 26. Valturna. Prescribing Information. Novartis Pharmaceuticals. May 2011. 27. Tekamlo. Prescribing Information. Novartis Pharmaceuticals. March 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ANTIPSYCHOTIC AGENTS for PATIENTS 17 YEARS OLD and YOUNGER FORMULARY STATUS: Preferred and Non-Preferred PA CRITERIA FOR APPROVAL: Appropriate Diagnosis/Indication for requested medication AND Appropriate dose of medication based on age (i.e. pediatric and elderly populations) and indication AND Documented trial and failure or intolerance with up to three formulary medications used to treat the documented diagnosis. For medications where there is only one formulary agent, only that agent must have been ineffective or not tolerated OR No other formulary medication has a medically accepted use for the patient s specific diagnosis as referenced in the medical compendia*. OR All other formulary medications are contraindicated based on the patient s diagnosis, other medical conditions, or other medication therapy. If the above conditions are met, the request will be approved with up to a 6 month duration depending upon the diagnosis and usual treatment therapies; if the above conditions are not met, the request will be referred to a Medical Director (or Psychiatrist when applicable) for medical necessity review. *Medical compendia consists of the following: the Food and Drug Administration (FDA) approved indication(s) (Drug Package Insert), Micromedex, American Hospital Formulary Service (AHFS), DrugPoints (formerly known as USPDI). Review Date: 11/2012 Associated Policy: Prior Authorization of Medications 236.200

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ANTIDEPRESSANT AGENTS for PATIENTS 5 YEARS OLD and YOUNGER FORMULARY STATUS: Preferred and Non-Preferred PA CRITERIA FOR APPROVAL: Appropriate Diagnosis/Indication for requested medication AND Appropriate dose of medication based on age (i.e. pediatric and elderly populations) and indication AND Documented trial and failure or intolerance with up to three formulary medications used to treat the documented diagnosis. For medications where there is only one formulary agent, only that agent must have been ineffective or not tolerated OR No other formulary medication has a medically accepted use for the patient s specific diagnosis as referenced in the medical compendia*. OR All other formulary medications are contraindicated based on the patient s diagnosis, other medical conditions, or other medication therapy. If the above conditions are met, the request will be approved with up to a 6 month duration depending upon the diagnosis and usual treatment therapies; if the above conditions are not met, the request will be referred to a Medical Director (or Psychiatrist when applicable) for medical necessity review. *Medical compendia consists of the following: the Food and Drug Administration (FDA) approved indication(s) (Drug Package Insert), Micromedex, American Hospital Formulary Service (AHFS), DrugPoints (formerly known as USPDI). Review Date: 11/2012 Associated Policy: Prior Authorization of Medications 236.200

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ANZEMET (dolasteron) Tablet: 50mg, 100mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Current treatment with emetogenic chemotherapy And Documented trial and failure with maximum therapeutic doses or intolerance to ondansetron tablet or oral disintegrating tablet (ODT) If the above condition is met, the request will be approved with quantity limit of 5 tablets/30days with a 3 month duration; if the above condition is not met, the request will be referred to a Medical Director for medical necessity review. If the request is for a quantity greater than 5 tablets/30days, the request will be referred to a Medical Director for medical necessity review. QUANTITIES GREATER THAN ABOVE LIMITS PER 30 DAYS: If the request is for a quantity greater than allowed per 30 days, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Prevention of postoperative nausea and vomiting. DOSAGE AND ADMINISTRATION: Prevention of chemotherapy induced nausea and vomiting: Adults: 100 mg within 1 hour before chemotherapy. Children (2 to 16 years of age): 1.8 mg/kg within 1 hour before chemotherapy, up to a maximum of 100 mg. Prevention of postoperative nausea and vomiting: Adults: 100mg within two hours before surgery. Children (2 to 16 years of age): 1.2mg/kg given within two hours before surgery, up to a maximum of 100mg. REFERENCE: 1. Bubalo J; Seelig F; Karbowicz S; Maziarz RT. Randomized open-label trial of dolasetron for the control of nausea and vomiting associated with high-dose chemotherapy with hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001;7(8):439-45. 2. The National Comprehensive Cancer Network (NCCN) and The American Cancer Society (ACS). Nausea and Vomiting. Treatment Guidelines for Patients with Cancer. Version IV. June 2007. 3. Steiner M, Yorgason RZ, Vermeulen LC, Theisen J. Patient outcomes after therapeutic interchange of dolasteron for granisetron. Am J Health-Syst Pharm 2003;60(10):1023-1028. 4. Markman M. Progress in preventing chemotherapy-induced nausea and vomiting. Cleve Clin J Med 2002 Aug;69(8):609-10, 612, 615-7. 5. Hesketh PI. Prevention and treatment of chemotherapy induced nausea and vomiting. February 2000. 6. American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006. Amercian Society of Clinical Oncology.J Clin Oncol.2006;24:1-16. 7. Anzemet (dolasetron) Product Information. Sanofi-Aventis, U.S. LLC. January 2011. 8. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION CRITERIA ARANESP (darbepoetin alfa): 25 mcg/ml, 40 mcg/ml, 60 mcg/ml, 100 mcg/ml, 200 mcg/ml, 300 mcg/ml, 500 mcg/ml PA CRITERIA FOR APPROVAL: The necessary lab work (listed below) is performed within 30 days of the date the request is submitted and is either documented on the PA form or submitted with the request -Hemoglobin -Hematocrit -Serum ferritin -Transferrin saturation (TSAT) -Serum iron -Total Iron Binding Capacity (TIBC) -Vitamin B12 level -Folate level -Erythropoietin level (for HIV related anemia) -Glomerular Filtration Rate (GFR) for chronic kidney disease related anemia Documentation submitted indicates the member has Chronic Kidney Disease related anemia and/or Chemotherapy related anemia, or anemia related to another specific medical condition. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the member into one of the following categories based on diagnosis: - Treatment of anemia of Patients with Chronic Kidney Disease go to Section I - Treatment of anemia in cancer patients undergoing chemotherapy: go to Section II - Prescribed for anemia in HIV and/or Zidovudine-treated HIV disease: go to Section III - Treatment of Ribavirin Induced anemia: go to Section IV - Prescribed for other Medically Acceptable Indications: go to Section V Section I: PA Criteria for Approval for anemia of Patients with Chronic Kidney Disease Place the member into one of the following categories based on the members Aranesp treatment history. - Aranesp treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp treatment initial request If the member has chronic kidney disease, The member has a hemoglobin level < 10 g/dl OR if the member is new to the health plan and was receiving Aranesp at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl If the member has anemia due to Pre-dialysis chronic kidney disease then documentation must be submitted that the member has a glomerular filtration rate (GFR) less than 60 ml/min/1.73m 2 for > 3 months OR meets the criteria for chronic kidney disease as defined by the National Kidney Foundation (see table 1) If the member has chemotherapy-related anemia then documentation is submitted indicating the member is currently receiving chemotherapy or has completed their course of chemotherapy within the past 30 days and: a. Hgb<10g/dL (submitted lab result dated within 30 days of request). b. Member is new to the health plan and was receiving Aranesp at the previous health plan and the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the member has low vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp If the member has chronic kidney disease, and has been receiving therapy and their hemoglobin is 12 g/dl (submitted lab result dated within 30 days of request), AND if one of the following apply: a. Ordered dose of Aranesp is reduced by 25% of previous dose if the member s Hgb is increasing by more than 1 g/dl in a 2 week period OR the Hgb is increasing and approaching 12g/dL b. The ordered dose of Aranesp is increased by 25% of the previous dose if the patient s Hgb improved 1g/dL over 4 weeks period (see Dosage and Administration section) and iron stores were accurate. c. No more than 1 dosage adjustment per 4 week intervals occurs If the member has chemotherapy-related anemia, documentation was submitted indicating the member is currently receiving chemotherapy or has completed their course of chemotherapy within the past 30 days AND hemoglobin is <12 g/dl (submitted lab result dated within 30 days of request) AND ONE OF THE FOLLOWING APPLY (if applicable): a. The ordered dose of Aranesp is reduced by 40% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Aranesp is increased to 300 mcg every 2 weeks if the patient s Hgb improved < 1g/dL over a 6 week period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. If the member had normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 and/or Folate based on lab results from the initial request and are NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored. Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved for up to a 3-month duration, if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section II: PA Criteria for Approval for anemia in cancer patients on chemotherapy: Place the member into one of the following categories based on the members Aranesp treatment history. - Aranesp treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp treatment initial request The member has a documented hemoglobin < 10g/dL OR if the member is new to the health plan and was receiving Aranesp at the previous health plan and the member has a documented hemoglobin < 12g/dL Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) Documentation that the patient is currently receiving chemotherapy (along with documentation of the start and end date of the current course of chemotherapy). Treatment with Aranesp should be discontinued at the completion of a course of chemotherapy.

If all of the above conditions are met, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp The member has been receiving therapy and their hemoglobin is < 12 g/dl Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the dose of Aranesp is being increased and/or patient s hemoglobin level has decreased from the previous request then recent (within 30 days of the request) ferritin, percentage transferrin saturation, Vitamin B12 and Folate levels are to be submitted. In addition: o If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), AND In the process of receiving either oral or IV iron supplementation OR The treatment plan is to start iron therapy along with having the percentage transferrin saturation and ferritin levels monitored. o If the member has low Vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is OR will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If all of the above conditions are met, and the member is not functionally iron (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%), Vitamin B-12 and Folate deficient OR if the member is iron, vitamin B12 and/or folate deficient and receiving the proper supplementation, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first). However, up to a 1 month temporary supply will be approved if the member is functionally iron (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or Vitamin B-12 or Folate deficient AND not receiving OR planning to start the proper supplementation. If the above criteria is not met, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section III: PA Criteria for Approval for Treatment of Anemia due to HIV and/or Zidovudine-treated HIV disease Place the patient into one of the following: - Aranesp treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp treatment initial request The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Aranesp at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl. Patient has been receiving a highly reactive antiretroviral therapy (HAART) regimen for the past 35 days. Documentation, within 30 days of the request, that the patient has a erythropoietin level < 500 units/ml. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested.

Part B: Reauthorization Criteria for Aranesp If the member has been receiving therapy AND hemoglobin is < 11 g/dl(submitted lab result dated within 30 days of request) OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dl ONE OF THE FOLLOWING APPLY: a. The ordered dose of Aranesp is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Aranesp is increased to 300 mcg every 2 weeks if the patient s Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below. Patient is currently receiving HAART therapy. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section IV: PA Criteria for Approval for Ribavirin Induced Anemia Place the patient into one of the following: - Aranesp treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp treatment initial request The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Aranesp at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. Patient is currently receiving ribavirin therapy and initiated therapy 20 weeks ago. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation

< 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp If the member has been receiving therapy AND hemoglobin is < 11 g/dl(submitted lab result dated within 30 days of request) OR hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dl ONE OF THE FOLLOWING APPLY: a. The ordered dose of Aranesp is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Aranesp is increased to 300 mcg every 2 weeks if the patient s Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. The member is currently receiving ribavirin therapy that was initiated 20 weeks ago, or if beyond week 20 of ribavirin therapy, documentation submitted indicates a dosage reduction of ribavirin to 600 mg/day after week 20 but the member still became anemic. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved with a 3-month duration or up to the member completes Ribavirin therapy (24-48 weeks of treatment), if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section V: PA Criteria for Approval for Treatment of Other Medically Acceptable Indications Place the member into one of the following categories based on the members Aranesp treatment history. - Aranesp treatment initial request (Part A) - Reauthorization of Aranesp (Part B) Part A: Aranesp treatment initial request Documentation was forwarded indicating the medication (including dose) was prescribed or recommended by a hematologist or a specialist in the respective disease state associated anemia. The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Aranesp at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl. The Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if

the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Aranesp If the member has been receiving therapy AND hemoglobin is < 11 g/dl (submitted lab result dated within 30 days of request) OR hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dl ONE OF THE FOLLOWING APPLY: a. The ordered dose of Aranesp is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Aranesp is increased by 25% of the previous dose if the patient s Hgb improved < 1g/dL over a 4 weeks period (See Dosage and Administration section) and iron stores were adequate. c. An increase in dose does not occur more than once per month. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), documentation was submitted indicating that the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored. Aranesp ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATIONS: Aranesp is indicated for: Treatment of anemia associated with chronic kidney disease (CDK), including in patients on dialysis and patients not on dialysis. Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies. o Aranesp is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy o Aranesp is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of Aranesp on progression-free and overall survival. o Aranesp use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being DOSAGE AND ADMINISTRATION: A. Chronic Kidney Disease patients on and not on dialysis: Therapeutic Guidelines in CKD Members for Aranesp Starting dose CKD patient on Dialysis 0.45 mcg/kg IV or SQ weekly OR 0.75 mcg/kg IV or SQ every 2 weeks (IV rout recommended for patients on hemodialysis) Starting Dose CKD patients not on Dialysis 0.45 mcg/kg IV or SQ at 4 week intervals

Reduce dose approximately 25% when If hemoglobin continue to increase despite a 25 % dosage reduction Dose should be temporarily withheld when Increase dose up to 25% of previous dose Maintenance dose Suggested target hemoglobin 1). Hemoglobin is increasing and approaching 11g/dL OR 2). Hemoglobin increased by more than 1.0 g/dl in 2-week period Hold dose temporarily until hemoglobin begins to decrease, then restart at a dose 25% below the previous dose. Hemoglobin exceeds 12 g/dl and until hemoglobin falls to 11 g/dl. Therapy should be reinitiated at a dose approximately 25% below the previous dose. If hemoglobin increases by less than 1g/dL over a 4 week period AND The member is not functionally iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%) nor deficient in vitamin B12 and folic acid. Functional iron deficiency and/or folic acid and/or vitamin B12 deficiency need to corrected prior to approval of any Aranesp doses that exceed the initial starting dose (0.75 mcg/kg administered every 2 weeks) Must to be individualized to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. Maintenance doses greater than the recommended initial starting dose (0.75 mcg/kg q2 weeks) will only be approved in members that do not have documented functional iron deficiency (ferritin concentration >100-800 ng/ml and percentage transferrin saturation>20-55%) nor deficient in vitamin B12 and folic acid. Between 10 g/dl and 12 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl B. Cancer members on chemotherapy, Anemia in HIV and/or Zidovudine-treated HIV disease, Ribavirin Induced anemia: Approvable Starting dose Subcutaneous administration 2.25 mcg/kg weekly OR 500 mcg SQ every 3 weeks Reduce dose approximately 25% of previous dose when Dose should be temporarily withheld when Increase dose to 4.5mcg/kg/week Approvable Maximum Dose for Chemo Therapy induce Anemia: 4.5 mcg/kg/week Maintenance dose 1). Hemoglobin is increasing and approaching 12 g/dl OR 2). Hemoglobin increased by more than 1.0 g/dl in 2-week period Hemoglobin exceeds 12 g/dl and until hemoglobin falls to 11 g/dl Therapy should be reinitiated at a dose approximately 40% below the previous dose. If hemoglobin increases by less than 1g/dL and remains below 10g/dL after 6 weeks of therapy AND The member is not functionally iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%) nor deficient in Vitamin B12 and Folic acid. Functional iron deficiency and/or folic acid and/or Vitamin B12 deficiency need to be corrected prior to approval of any Aranesp doses that exceed the initial starting dose Must be individualized Maintenance doses greater than the recommended initial starting dose (2.25mcg/kg/weekly OR 500mcg every 3 weeks) will only be approved in members that do not have documented functional iron deficiency (ferritin concentration >100-800 ng/ml and percentage transferrin saturation >20-55%) nor deficient in Vitamin B12 and Folic acid. ***Dose should be adjusted for each patient to maintain the lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. *** Suggested target Hemoglobin Target Hgb < 12 g/dl for cancer patients on chemotherapy and <12 g/dl for Anemia in HIV and/or Zidovudine-treated HIV disease or Ribavirin Induced anemia or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. C. Other Medically Acceptable Indications Dosing Guidelines: Based on the medical compendia (Drug Points, Micro Medex, AHFS) and standard of care clinical guidelines, the dose is appropriate for the medically acceptable indication being treated, or is equivalent to the recommended Procrit dose as

indicated below under Conversion from epoetin alfa (Procrit ) to darbepoetin. If the member was receiving Procrit, the ordered dose of Aranesp is equal to the recommended dosage conversion as indicated below under Conversion from epoetin alfa (Procrit ) to darbepoetin. Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dl in a 2-week period Or Hemoglobin is increasing and approaching 12 g/dl o Temporarily hold dose when: Hgb exceeds 12 g/dl and until Hgb falls to below 11 g/dl Therapy can be reinitiated at a dose approximately 25% below the previous dose o Increase dose by 25%, if the member s Hgb does not increase by 1 g/dl after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient Target Hgb: <12 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl D. Conversion from epoetin alfa (Procrit ) to darbepoetin: Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Because of the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if member was receiving epoetin alfa 2 to 3 times weekly. Administer darbepoetin once every 2 weeks if the member was receiving epoetin alfa once per week. Maintain the route of administration (IV or SC). Estimated Darbepoetin Starting Doses Based on Previous Epoetin Alfa Dose Previous weekly epoetin alfa dose Equivalent weekly starting darbepoetin dose (mcg) (units/week) < 2500 6.25 2500 to 4999 12.5 5000 to 10,999 25 11,000 to 17,999 40 18,000 to 33,999 60 34,000 to 89,999 100 90,000 200 TABLE 1 The Definition of Chronic Kidney Disease The KDOQI defines Chronic Kidney Disease with two independent criteria: 1. Kidney damage for > 3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either: Pathological abnormalities OR Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests 2. GFR < 60 ml/min/1.73m2 for >3 months with or without kidney damage

National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39: S1- S266, 2002 (suppl 1). REFERENCES: 1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, 2000. Am J Kidney Dis 37:S182-S238, 2001 (suppl 1) 2. Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS. Use of Epoetin in Patients with Cancer: Evidence-Based Clinical Practice Guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Journal of Clinical Oncology, Vol 20, No. 19 (October 1), 2002: pp 4083-4107. Available from URL: http://www.asco.org/asco/downloads/guidelines/2002epo.pdf 3. Lichtin A. The ASH/ASCO clinical guidelines on the use of erythropoietin. Best Practice & Research Clinical Haematology. 2005; 18(3):433-438. 4. Suranyi M, Lindberg J, Navarro J, and Brenner R et al. Treatment of anemia with Darbepoetin Alfa Administered de novo Once Every Other Week in Chronic Kidney Disease. Am J Nephrology. 2003; 23:106-111. 5. Volberding PA, Levine AM, Dietrich D, et al. Anemia in HIV Infection: Clinical Impact and Evidence-Based Management Strategies. Clinical Infectious Diseases 2004;38:1459-68 6. HIV and AIDS Anemia and Fatigue. [resource on World Wide Web]. URL: http://www.hivandhepatitis.com/recent/lipo/071902_anemia.html#who 7. Schwartzberg L, Shiffman R, and Tomita D et al. A Multicenter Retrospective Cohort Study of Practice Patterns and Clinical Outcomes of the Use of Darbepoetin alfa and Epoetin Alfa for Chemotherapy-Induced Anemia. Clinical Therapeutics; vol.25, No.11: 2003. 8. Navarro J, roger S, and Churchill D et al. Aranesp Administered Once Every Other Week Treats Anemia in Patients with Chronic Kidney Disease Not Receiving renal Replacement Therapy. Journal of American Society of Nephrology.vol. 13, No. 9:2002 9. Patton, J, Wallace J. Darbepoetin alfa 200mcg Every 2 Weeks and Epoetin alfa 40,000 U Every Week in Chemotherapy Induced Anemia Patients Result in Similar Initial Hemoglobin Outcomes. ISPOR: 2003. 10. Schwartzberg L, Yee L, and Senecal F et al. Darbepoetin 200mcg Every 2 Weeks vs Epoetin alfa 40,000 U Weekly in Anemic Patients Receiving Chemotherapy. American Society of Clinical Oncology Meeting Proceedings, Volume 23: 2004. 11. Thames W, Smith S, and Scheifele A et al. Evaluation of the US Oncology Network s Recommended Guidelines for Therapeutic Substitution with Darbepoetin alfa 200mcg Every 2 Weeks in Both Naïve Patients and Patients Switched from Epoetin alfa. Pharmacotherapy 2004; 24(3):313-323. 12. Agarwal A, Ling B, and Walczyk M et al. Aranesp administered once monthly maintains hemoglobin levels in patients with chronic kidney disease.2004 National Kidney Foundation Clinical Meeting: April 28-May 2, 2004.Chicago, IL. Poster# 86. 13. Agarwal A, Ling B, and Walczyk M et al. Aranesp administered once monthly maintains hemoglobin levels in patients with chronic kidney disease. American Journal of Kidney Diseases;vol 43, No 4: April 2004. 14. Aranesp (darbepoetin alfa). Prescribing Information, Amgen. 7/2012 15. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cancer and Treatment-Related Anemia. Version 1.2008. Review Date: 07/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Avastin (bevacizumab): 100 mg/4 ml & 400 mg/16 ml vials FORMULARY STATUS: Non Formulary PRIOR AUTHORIZATION CRITERIA: The following information must be documented on the PA form or submitted with the request: 1. Documentation submitted indicates an oncologist prescribed the Avastin and it is being prescribed at an FDA approved or medically accepted dosage. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. If all of the above conditions are met, place the member into one of the following categories based on diagnosis. FOR INITIAL APPROVAL FOR BREAST CANCER: PA Criteria for Initial Approval 1. Documentation submitted that Avastin is being used concurrently with generic paclitaxel. 2. Documentation submitted that the patient has human epidermal growth factor receptor-2 (HER2) negative. If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review. FOR INITIAL APPROVAL FOR COLORECTAL CANCER: PA Criteria for Initial Approval 1. The member has documented metastatic cancer of the colon or rectum 2. Documentation that the Avastin is being used in combination with a 5-fluorouracil-based chemotherapy. If the above conditions are met, the request will be approved for up to a 12-week duration, if all of the above are not met, the request will be referred to a Medical Director. FOR INITIAL APPROVAL FOR LUNG CANCER: PA Criteria for Initial Approval 1. Documentation that the patients has a clinical diagnosis of non-squamous, non-small cell lung cancer 2. Documentation that the Avastin is being used in combination with carboplatin and paclitaxel If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review. FOR INITIAL APPROVAL FOR KIDNEY (RENAL CELL) CANCER: PA Criteria for Initial Approval 1. Documentation that the patient has a clinical diagnosis of metastatic renal cell carcinoma. 2. Documentation that the patient has had a documented trial and failure with Votrient If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review. FOR INITIAL APPROVAL FOR GLIOBLASTOMA: PA Criteria for Initial Approval 1. Documentation that the patient has a clinical diagnosis of glioblastoma. 2. Documentation that the patient has had a trial and failure on a prior treatment option. If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review. REAUTHORIZATION CRITERIA: 1. Documentation submitted indicates that the member has been tolerating Avastin therapy 2. Documentation submitted indicates an oncologist prescribed the Avastin at an FDA approved or medically accepted dosage. If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review.

PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints, and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). If all of the above conditions are met, the request will be approved for a duration of up to 12 weeks. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints, and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication If all of the above conditions are met, the request will be approved for a duration of up to 12 weeks. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATIONS: Avastinis indicated for use: In combination with intravenous 5-flourouracil-based chemotherapy for first or second line treatment of patients with metastatic carcinoma of the colon or rectum. In combination with carboplatin and paclitaxel for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer. In combination with paclitaxel is indicated for the treatment of patients who have not received chemotherapy for metastatic HER2 negative breast cancer. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. As a single agent in the treatment of glioblastoma with progressive disease following prior therapy. In combination with interferon alfa in the treatment of metastatic renal cell carcinoma. DOSAGE AND ADMINISTRATION: Metastatic Carcinoma of the Colon or Rectum: When given in combination with intravenous 5-flourouracil chemotherapy, Avastin should be given as an intravenous infusion at 5 mg/kg or 10 mg/kg every 14 days. When given in combination with bolus irinotecan, leucovorin and fluorouracil (IFL) chemotherapy, the recommended dose of Avastin is 5 mg/kg. When given in combination with FOLFOX4, the recommended dose of Avastin is 10 mg/kg. Non-Squamous, Non-Small Cell Lung Cancer: The recommended dose of Avastin is 15 mg/kg as an IV infusion every 3 weeks. Metastatic Breast Cancer: The recommended dose of Avastin is 10 mg/kg as an Infusion every 14 days.

Glioblastoma The recommended dose is 10 mg/kg every 2 weeks. Metastatic Renal Cell Carcinoma The recommended dose is 10 mg/kg every 2 weeks in combination with interferon alfa. There are no dose modifications recommended. If member develops one of the following conditions, Avastin therapy should be permanently discontinued: Gastrointestinal perforation, fistula formulation, and/or intra-abdominal abscess. Wound dehiscence Serious hemorrhages or bleeding Severe arterial thromboembolic event Nephrotic syndrome Hypertensive crisis or hypertensive encephalopathy Avastin therapy should be temporary suspended: Moderate to severe proteinuria 30 days pre- and post-operative surgery Severe hypertension that is not controlled with medical management. REFERENCES: 1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Colon Cancer. V.2.2009. 2. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Breast Cancer. V.1.2010. 3. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Rectal Cancer. V.2.2009. 4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. V.2.2009. 5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Kidney Cancer. V.2.2010. 6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Rectal Cancer. V.2.2009. 7. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Central Nervous System Cancer. V.2.2009. 8. AVASTIN Product Information. Genentech Inc. February 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA AVINZA (morphine sulfate extended release) Capsule: 30mg, 45mg, 60mg, 75mg, 90mg, 120mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of moderate to severe pain requiring opioid analgesic for extended period of time. AND Documented trial and failure or intolerance to generic morphine sulfate extended release tablets. AND Documented trial and failure or intolerance to Kadian. If the above conditions are met, the request will be approved with a 6-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Intended for once daily administration indicated for the relief of moderate to severe pain requiring continuous, around the clock opioid therapy for an extended period of time. Not intended for prn use. DOSAGE AND ADMINISTRATION: All doses are intended to be administered once daily. Maximum daily dose which must be adhered to is 1600mg/day. Conversion from Other Oral Morphine Formulations to Avinza: Patients receiving other oral morphine formulations may be converted to AVINZA by administering the patient s total daily oral morphine dose as AVINZA once-daily. AVINZA should not be given more frequently than every 24 hours. As with conversion from any oral morphine formulation to another, supplemental pain medication may be required until the response to the patient s daily AVINZA dosage has stabilized (up to 4 days). Conversion from Parenteral Morphine to Avinza: Anywhere from 3 to 6 mg of oral morphine may be required to provide pain relief equivalent to 1 mg of parenteral morphine. Based on this rationale, a reasonable starting dose of AVINZA would be approximately three times the previous daily parenteral morphine requirement. Conversion from Other Parenteral or Oral Non-Morphine Opioids to Avinza: Physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion rates are only approximate. In general, it is safest to administer half of the estimated daily morphine requirement as the initial AVINZA dose once per day and then manage insufficient pain relief by supplementation with immediate-release morphine or other short-acting analgesics. WARNING: Must be swallowed whole (not chewed, crushed, or dissolved). May be opened and the entire bead contents sprinkled on a small amount of applesauce immediately prior to ingestion. The beads may not be chewed, crushed or dissolved due to the risk of rapid release and absorption of a potentially fatal dose of morphine. Patients must not consume alcoholic beverages while on AVINZA therapy. Additionally, patients must not use prescription or non-prescription medicine containing alcohol while on AVINZA therapy. Consumption of alcohol while taking AVINZA may result in the rapid release and absorption of a potentially fatal dose of morphine. The daily dose must be limited to a maximum of 1600mg/day. Doses above 1600mg/day contain a quantity of fumaric acid that has not been demonstrated to be safe, and which may result in serious renal toxicity. The 45, 60, 75, 90, and 120mg capsules are for use only in opioid-tolerant patients. REFERENCES: 1. Ballantyne JC, Mao J. Opioid therapy for chronic pain. NEJM 2003;349(20):1943-1953 2. Tassain V, Attal N, Fletcher D, Brasseur L, et al. Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain. Pain 2003;104(2):389-400 3. Portenoy RK; Sciberras A; Eliot L; Loewen G; Butler J; Devane J. Steady-state pharmacokinetic comparison of a new, extended-release, once-daily morphine formulation, Avinza, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain. J Pain Symptom Manage 2002 Apr;23(4):292-300

4. Caldwell JR, Rapoport RJ, Davis JC, et al. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Manage (United States), Apr 2002, 23(4) p278-91 5. American Cancer Society (ACS). National Comprehensive Cancer Network (NCCN). Cancer Pain. Treatment Guidelines for Patients. Version I. January 2001 6. World Health Organization. Geneva. 1996. Cancer Pain Relief. Second Edition. With a guide to Opioid Availability. 7. Morphine oral--elan Corporation. Avinza. Drugs R D (New Zealand), 2002, 3(3) p208-9 8. National Institutes of Heath. National Heart, Lung and Blood Institute. Division of Blood Diseases and Resources. The Management of Sickle Cell Disease. NIH Publication No. 02-02117. June 1997, Revised June 2002 9. Facts and Comparisons, St. Louis, efacts 2011 CliniSphere Version ISBN 1-57439-036-8 10. Kadian Product Information. Actavis Elizabeth LLC. February 2010. 11. Avinza Product Information. King Pharmaceuticals, Inc. April 2008. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

BACTROBAN (mupirocin) Nasal Ointment 2%: 1g FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Use is consistent with pre-operative prophylaxis of S. aureus TRUE HEALTH PRIOR AUTHORIZATION CRITERIA If the above conditions are met, the request will be approved with a 5 day duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Eradication of nasal colonization with methicillin-resistant S. aureus in adult patients and health care workers as part of a comprehensive infection control program to reduce infection risk among patients at high risk of methicillin-resistant S. aureus infection during institutional outbreaks of infections with this pathogen. DOSAGE AND ADMINISTRATION: Divide approximately one half of the ointment from the single-use tube between the nostrils and apply twice daily (morning and evening) for 5 days. Note: Bactroban Nasal is NOT FDA Indicated for: Prevention of postoperative nosocomial Staphylococcus aureus infections General prophylaxis of any infection in any patient population Application on other parts of the body REFERENCES: 1. Custer JW, Rau RE, eds. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 18th ed. Philadelphia, PA: Mosby/Elsevier; 2009. 2. Bactroban Nasal Ointment. Prescribing Information. GlaxoSmithKline. August 2001. 3. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 4. Young TE, Mangum B. NeoFax 2009. 22nd ed. Montvale, NJ: Thomson Reuters; 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA BANZEL (rufinamide) Tablet: 200mg, 400mg FORMULARY STATUS Non-Formulary Oral Suspension: 40mg/mL PA CRITERIA FOR APPROVAL Diagnosis of Lennox-Gastaut syndrome. Patient is currently receiving another anticonvulsant medication at a therapeutic dosage. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a psychiatrist for medical necessity review. FDA INDICATIONS For adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. DOSAGE AND ADMINISTRATION Children Four Years and Older with Lennox-Gastaut Syndrome: Treatment should be initiated at a daily dose of approximately 10mg/kg/day administered in two equally divided doses. The dose should be increased by approximately 10mg/kg increments every other day to a target dose of 45mg/kg/day or 3200mg/day, whichever is less, administered in two equally divided doses. It is not known whether doses lower than the target doses are effective. Adults with Lennox-Gastaut Syndrome: Treatment should be initiated at a daily dose of 400-800mg/day administered in two equally divided doses. The dose should be increased by 400-800 mg/day every 2 days until a maximum daily dose of 3200mg/day, administered in two equally divided doses is reached. It is not known whether doses lower than 3200mg are effective. Banzel tablets are scored on both sides and can be cut in half for dosing flexibility. Tablets can be administered whole, as half tablets or crushed. Banzel should be given with food. Oral Suspension should be shaken well before every administration. The provided adapter and calibrated oral dosing syringe should be used to administer the oral suspension. The provided adapter should be inserted into the bottle neck and remain there for the duration of usage of the bottle. REFERENCES 1. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Banzel. Prescribing Information. Eisai Inc. March 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Psychiatrist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION PROTOCOL FOR BOTULINUM TOXINS A & B Botulinum toxin type A: (Botox ) Powder for Injection (vacuum dried), preservative free, single-use vials containing Clostridium botulinum toxin type A 100 units [contains 0.5 mg human albumin, 0.9 mg sodium chloride] Botulinum toxin type B: (Myobloc ) Injectable solution, preservative-free, containing 5,000 units/ml of botulinum toxin type B (0.5 ml, 1 ml, 2 ml single- use vials) [contains albumin 0.05% human serum albumin, 0.01 M sodium succinate, 0.1 M sodium chloride] FORMULARY STATUS: MYOBLOC PREFERRED IN SELECT DISEASE STATES Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition (See Medically Accepted Uses section below) that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), Drug Package Insert) as defined in the Social Security Act 1927 and/or per Standard of Care Guidelines in each respective disease state. AND Documentation was submitted, that the patient has a (consistent with pharmacy claims data) adequate trial (including dates of treatment at maximum recommended doses of therapy) of standard conventional first line therapy for their respective disease state (where applicable) as recommended by the medical compendia and standard of care guidelines and/or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking standard conventional first line therapy to treat their medical condition. AND If the medication request is for Botulinum toxin type A (Botox ) for treating the following medical conditions: Spasmodic Torticollis (Cervical Dystonia), Severe Primary Axillary Hyperhidrosis, Bladder Muscle Dysfunction (overactive), Excessive Salivation in Parkinson, Incontinence in Spinal Cord Injury, Spastic Dysphonia, Upper Limb Spasticity from Cerebral Vascular Accidents or from Traumatic Brain Injury, the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial (including dates, 3 months or more of therapy) of Botulinum toxin type B (Myobloc ) and/or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing Botulinum toxin type B (Myobloc ) to manage their medical condition. AND Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per Standard of Care Guidelines in each respective disease state. If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per Standard of Care Guidelines in each respective disease state; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per Standard of Care Guidelines in each respective disease state. AND Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per Standard of Care Guidelines in each respective disease state. If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per Standard of Care Guidelines in each respective disease state; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Medically Accepted Dosing: Botulinum toxin type B: (Myobloc ) Spasmodic torticollis (cervical dystonia) - (FDA approved): 2400-10,000 units IM divided among affected muscles. Response duration of up to 4 months in some patients. Severe Primary Axillary Hyperhidrosis: - 250-200 units injected into 10 to 15 sites in each axilla. Doses as high as 2000-5000 units per axilla have been used. Response duration 2 to 8 months (avg 5 months). Bladder Muscle Dysfunction (overactive): 2500-15,000 units injected into the bladder wall at different sites. Response duration of 3 weeks to 3 month.

Excessive Salivation in Parkinson: 1000 units into each parotid gland and 250 units into each submandibular gland. Response duration of up to 20 weeks. Incontinence in Spinal Cord Injury: 5000 units into detrussor muscle sites (trigone typically exempt). Response duration of up to 1 month. Spastic Dysphonia: 500-750 units into thyroarytenoid muscles. 25-100 units to each vocal cord via the cricothyroid membrane. Response duration of up to 14 weeks. Upper Limb Spasticity from Cerebral Vascular Accidents or from Traumatic Brain Injury: 5000-17,500 total limb dose divided into specific muscles. Average of 375-2500 for arm muscles. Response duration from 4 to 12 weeks. Additional Dosing Information: See Appendix I - entitled Practical Considerations for the Clinical Use of Botulinum Toxin Type B Medically Accepted Dosing For Some Common Diseases: Botulinum toxin type A: (Botox ) Spasmodic torticollis (cervical dystonia) (FDA approved): 100 to 300 Units (lower dose for patients without prior use of botulinum toxin to limit incidence of dysphagia) divided among affected muscles; limit total dose to 100 Units or less may decrease the incidence of dysphagia. Response duration up to 3 months. Blepharospasm (FDA approved) (Adult and Pediatric): 1.25-2.5 units into injected into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid. The cumulative dose in a 30-day period should not exceed 200 units. Response duration up to 3 months. Repeat treatments needed prior to 3 months are considered insufficient and the dose can be increased up to two-fold up to 5 units per site. Strabismus (FDA approved): The volume of injected for treatment of strabismus should be between 0.05-0.15 ml per muscle. Use the lower listed doses for treatment of small deviations. Use the larger doses only for large deviations. Initial doses: For vertical muscles and for horizontal strabismus of less than 20 prism diopters: 1.25-2.5 units in any one muscle. For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5-5.0 units in any one muscle. For persistent VI nerve palsy of one month or longer duration: 1.25-2.5 units in the medial rectus muscle. Subsequent doses for residual or recurrent strabismus: It is recommended that patients be re-examined 7-14 days after each injection to assess the effect of that dose. Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose comparable to the initial dose. Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to two-fold compared to the previously administered dose. The cumulative dose in a 30-day period should not exceed 200 units. Subsequent injections should not be administered until the effects of the previous dose have dissipated as evidenced by substantial function in the injected and adjacent muscles. The maximum recommended dose, as a single injection for any one muscle, is 25 units. Severe Primary Axillary Hyperhidrosis Inadequately Managed by Topical Agents (FDA approved): The recommended dose is 50 units per axilla. Retreatment when clinical effect diminished. Bladder Muscle Dysfunction (overactive, neurogenic): 200-300 units injected IM into the detrusor muscle. Response duration up to 24 weeks. Excessive Salivation in Parkinson, Multiple System Atrophy, Neulogical Disorders, Bulbar Amyotrophic Lateral Sclerosis (Adult and Pediatric): 5-30 units injected in divided doses into the parotid and submandibular glands at doses calculated by patient weight and rate of salivation. Response duration from 1 to 3 months. Incontinence in Spinal Cord Injury or Trauma: 80-100 units given as a single injection or monthly for 2-3 months. Single injection method response duration is about 2-3 months; monthly injection method response duration is 9-13 months. Spastic Dysphonia: Average dose of 10 units per side with higher doses up to 20 units required for abductor and adductor laryngeal involvement. Response duration up to 6 months. Upper Limb Spasticity from Cerebral Vascular Accident: 75-300 units divided among affected muscles. Response duration about 12 weeks.

Upper Limb Spasticity from Traumatic Brain Injury: dose depends on muscle injected. Doses range from 20 to 300 units injected in divided doses to affected muscles. Response duration about 4-6 months. Lower Limb Spasticity from Cerebral Vascular Accident or Traumatic Brain Injury: 20-500 units injected in divided doses to affected muscle group. Response duration 8-12 weeks. Lower limb spasticity has inconclusive evidence on efficacy. Abducens Nerve Palsy: 2.5-5 units injected into the medial rectus muscles. Response duration from 3-6 months. Achalasia: 80-100 units injected into the lower esophageal sphincter. Response duration 1 year. Auriculotemporal Syndrome (Frey s Syndrome): 1-2 units per 2.25 cm2 of hyperhidrotic skin as visualized by the iodine starch test. Total dose 21-65 units. 1-3 sessions necessary. Response duration from 6-12 months. Fibromyalgia: 80-200 units injected into affected muscles. Response duration up to 2 months. Hemifacial spasm: 15-30 units divided among affected muscles. Response duration from 3 to 5 months. Lower limb Spasticity in Multiple Sclerosis: 155-400 units divided among affected muscles per session. Response duration 1-3 months. Essential Tremor: 50-200 units divided among affected muscles. Response duration from 4 to 10.5 weeks. Cerebral Palsy (CP): Used to improve motor function and gait, relieve pain, and enhance self-esteem and health-related quality of life in children with spasticity associated with CP (hemiplegia, diplegia) who do n ot have substantial fixed contractures. Goal of treatment with botulinum toxin is to reduce spasticity and muscle imbalance by weakening agonist muscles without affected antagonist muscles. For lower-limb spacticity in pediatric CP: candidates for treatment with botulinum toxin include those with dynamic equines persistent throughout the gait cycle, equinovarus deformity, a dynamic knee flexion angle exceeding 20 degrees during the gait cycle or one that interferes with gait, or substantial scissoring and adduction at the hips. For upper-limb spacticity in adult (up to 21 y/o) and pediatric CP: candidates for treatment with botulinum toxin include those with persistent thumb in palm or thumb adduction, wrist posture that prevents effective use, or tight elbow flexion. Dose: 1-8 units/kg divided among affected muscles. Response duration typically 1 to 3 months. Myofascial Pain Syndrome: 50-150 units depending upon the injected muscle. Response duration is based on relief of pain. Documentation must be submitted that the patient failed first line therapy consisting of injections of local anesthetics and corticosteroids to trigger points as well as massage and physical therapy, and lifestyle changes to reduce stress. Migraine: for disabling primary headaches (migraine, tension-type): total dose 25-75 units divided among 11 standardized areas in the frontalis, temporalis and glabellar muscles. Response duration up to 4 months. Oromandibular Dystonia: For jaw-closing type use 25-50 units into each masseter muscle. If satisfactory results are not obtained, 5-40 units may be injected into each temporalis muscle. Response duration 2-4 months. For complete medically acceptable dosing information: See Medical Compendia as defined by the Social Security Act (USP-DI, AFHS, Micromedex, Drug Package Insert) and appropriate standard of care guidelines for respective disease state. HOW SUPPLIED: Myobloc is supplied as a clear and colorless to light yellow sterile injectable solution in single-use 3.5 ml glass vials. Each singleuse vial contains 5000 units of botulinum toxin type B per ml. To ensure that the labeled volume of Myobloc is delivered, vials of are over filled during the manufacturing process. The amounts are listed below: How Myobloc is supplied Myobloc 2500units/0.5 ml Myobloc 5000units/1.0 ml Myobloc 10,000units/2.0 ml Amount with the overfill 0.82mL 1.36mL 2.53mL The units corresponding with the overfill 4100 units 6800 units 12,650 units Botox is supplied as a single use vial containing 100 units of vacuum-dried Clostridium botulinum type A neurotoxin complex. DOSAGE AND ADMINISTRATION:

Patients without a prior history of tolerating botulinum toxin injections should receive a lower initial dose. Subsequent dosing should be optimized according to the patient s individual response. Units of biologic activity of Myobloc and Botox cannot be compared to or converted into units of any other botulinum toxin or any toxin assessed with any other specific assay method. Clinical studies have shown that 1 unit of Botox is approximately equivalent to 30-50 units of Myobloc. The 1:30 conversion is used for Cerebral Palsy. Myobloc may be diluted up to 6 fold and maintain its structural integrity. For greatest accuracy in final concentration, dilution should be performed in the syringe, not in the vial, due to the overfill in the vials. To dilute, draw medication into syringe, then draw up saline to desired volume. Example: To deliver 1000 units in 0.6 ml, draw 0.2 ml toxin into syringe then add 0.4 ml saline for a final volume of 0.6 ml. Administration Guide for Myobloc Clinical Situation Start at the low end of the range if: Start at the high end of the range if: Patient Weight Low High Muscle Bulk Very Small Very Large Disease Severity Mild Severe Concern for Weakness High Low Results of Previous Therapy Too Much Weakness N/A Starting Myobloc Dose Recommendations for Adults (this may not apply in all situations) Total maximum dose per visit = 10,000 to 15,000 units Maximum dose per injection site = 2500 units Maximum volume per site = 0.5 ml Reinjections 3 months For Specific Dosing of Myobloc per muscle and dilution ratios see Appendix I entitiled Practical Considerations for the Clinical Use of Botulinum Toxin Type B. Botox requires reconstitution with sterile, preservative-free 0.9% sodium chloride. See dilution table: Diluent Added (0.9% Sodium Chloride Injection) Resulting Dose in Units per 0.1 ml 1.0 ml 10.0 units 2.0 ml 5.0 units 4.0 ml 2.5 units 8.0 ml 1.25 units These dilutions provide a 0.1 ml injection volume. A required dose, which is higher or lower than what appears on the table, can be obtained by administering a smaller or larger volume. Example: If 15 units is required give 0.15 ml volume of the 10 unit/0.1 ml dilution. PRECAUTIONS: Coadministration of botulinum toxin with aminoglycosides or other agents interfering with neuromuscular transmission such as curare-like compounds may potentate effect of toxin. Medically Accepted Uses: Botulinum toxin type B: (Myobloc ) Bladder muscle dysfunction - overactive Spasmodic torticollis Excessive salivation (sialorrhea) in Parkinson Spastic dysphonia Severe primary axillary hyperhidrosis Upper limb spasticity - (CVA) Incontinence - Spinal cord injury *Wrinkled face, hyperfunctional (not a covered indication) * Note: Use of these medications for cosmetic purposes is not a covered benefit under the Medical Assistance Program. Myobloc has been used in the following disease states: blepharospasm, cerebral palsy (500-600 units/kg, 8000 units/limb), oromandibular dystonia, lingual dystonia, hemifacial spasm, headache, upper and lower limb dystonia and lower limb spasticity. Ongoing trials are occurring. Consensus panels of clinicians who are experienced in the use of botulinum toxin type B therapy have established dosing recommendations for these disease states. It would be acceptable if an ordering physican prefers to use Myobloc instead of Botox for one of these indications due to experience with the product. There may be a medical reason for preferring Myobloc over Botox (i.e. treatment failure to botulinum toxin type A due to antibodies to Botox, etc.) See Appendix I entitiled Practical Considerations for the Clinical Use of Botulinum Toxin Type B for additional information on dosing and medical uses for Myobloc. Botulinum toxin type A: (Botox )

Abducens nerve palsy Achalasia Auriculotemporal syndrome (Frey s syndrome) Back pain, chronic lower Benign prostatic hyperplasia Bladder muscle dysfunction - overactive, Neurogenic Blepharospasm (Adult and Pediatric) Cerebral palsy - Lower limb spasticity (adult and pediatric) Cerebral palsy - Upper limb spasticity (pediatric) Cerebrovascular accident - Lower limb spasticity (evidence is inconclusive) Cerebrovascular accident - Upper limb spasticity Cervicogenic headache-(whiplash headache) Esophageal motility disorders Dystonia Epicondylitis Essential tremor Excessive Salivation (sialorhea) in Parkinson, Multiple System Atrophy, Neulogical Disorders, Bulbar Amyotrophic Lateral Sclerosis (Adult and Pediatric) Facial myokymia Fibromyalgia Flushing of neck and anterior wall Gilles de la Tourette's syndrome Hemifacial spasm Hyperhydrosis disorder, Non-axillary (adult and pediatric) Lichen simplex chronicus Lower limb spasticity - Multiple sclerosis Migraine Mucocele of salivary gland (recurrent sialocele following parotid surgery) Myofascial Pain Syndrome Oromandibular Dystonia Pelvic floor dyssynergia/anismus (intractable constipation) Procedure on eye region; Adjunct (adult and pediatric) *Rhytidoplasty of eyelid (not a covered indication) Severe Primary Axillary Hyperhidrosis Inadequately Managed by Topical Agents Spasmodic torticollis Spastic dysphonia Strabismus (adult and pediatric) Tardive dyskinesia as a result of long-term neuroleptic use) Temporomandibular joint disorder Traumatic brain injury (Upper and Lower limb spacticity) Whiplash injury to neck pain and range of motion *Wrinkled face, hyperfunctional (not a covered indication) * Note: Use of these medications for cosmetic purposes is not a covered benefit under the Medical Assistance Program. Glossary: Achalasia: a condition in which the lower esophageal sphincter fails to relax adequately during swallowing. Anismus (Pelvic floor dyssynergia): is an example of anorectal dysfunction that can contribute to constipation. It is characterized by failure of pelvic floor muscles to relax or a paradoxical contraction of the pelvic floor muscles with defecation. Auriculotemporal Syndrome (Frey s syndrome): is an auditory disorder distinguished by excessive sweating of the forehead, upper lip, perioral region or sternum following gustatory stimuli. The auriculotemporal syndrome features facial flushing or sweating limited to the distribution of the auriculotemporal nerve and may develop after trauma to the parotid gland in association with parotid neoplasms or following surgical removal. Blepharospasm: is a chronic, debilitating, focal dystonia that causes involuntary closure, twitches or tics of the eyelids (orbicularis oculi). It may affect other muscles of the face and neck, as well, and can cause impairment of daily activities and functional blindness in severe cases. Cervical Dystonia (spasmodic torticollis): is a focal dystonia, with the presence of sustained simultaneous contractions of agonists and antagonists muscles of the neck causing abnormal movements and posture of the head and neck. The movements may be sustained or jerky. Spasms in the muscles or pinching nerves in the neck can result in considerable pain and discomfort. Cervical dystonia should not be confused with other conditions, which cause a twisted neck such as local orthopedic, congenital problems of the neck, ophthalmologic conditions where the head tilts to compensate for double vision. It is sometimes misdiagnosed as stiff neck, arthritis, or wryneck. Primary Cervical Dystonia: is believed to be due to abnormal functioning of the basal ganglia, which are deep brain structures involved with the control of movement. The basal ganglia assist in initiating and regulating movement. An imbalance of dopamine, a neurotransmitter in the basal ganglia, may trigger several different forms of dystonia, but the exact cause is still unknown. Secondary Forms of Dystonia: are the results of numerous causes, such as birth injury, trauma, toxins, or stroke. Secondary dystonia can be symptomatic and can also occur in association with other disorders such as Wilson's disease. Adult-onset (>28 y/o) focal dystonias that are presumed to be primary e.g., based upon thorough clinical examination, a complete patient and family history, nature of the dystonia, absence of certain signs upon examination, etc. experts indicate that extensive laboratory or neuroimaging studies may not be necessary. If patients are under 40 years of age, they should receive specific tests to help exclude Wilson disease. (copper accumulation in the brain). Early-onset (<28 y/o) generalized or segmental limb dystonia who test negative for the DYT1 gene mutation, physicians may recommend a diagnostic trial with the agent levodopa (L-dopa). The dystonia-plus syndrome known as dopamine-responsive dystonia (DRD) is suggested in young

patients with dystonia who have significant improvement with low-dose L-dopa therapy. In contrast, most dystonia patients who do not have DRD do not have a response to treatment with L-dopa or dopamine agonists. Thus, if no improvement is noted after approximately 3 months of L-dopa therapy, a diagnosis of DRD is considered unlikely and such treatment may be stopped. Hemifacial spasm: is caused by abnormal stimulation of the facial nerve VII, resulting in contraction of muscles typically involving the eyelid, mouth and cheek. Patients display intermittent or continuous twitching on one side of the face. Hyperhidrosis: is defined as excessive and uncontrollable sweating in the axilla, on the palms of the hands and on the soles of the feet. The profuse sweating can lead to skin maceration and secondary bacterial infections. The hyperhidrosis is a result of sympathetic hyperactivity of the eccrine sweat glands. The eccrine glands are innervated by sympathetic nerves that use acetylcholine (ACh) as the neurotransmitter. The botulinum toxin affects the excessive sweat production by blocking the release of ACh in the postganglionic sympathetic fibers in these eccrine glands. Oromandibular dystonias: (ex: Meige s syndrome), which are characterized by continuous, bilateral, asynchronous muscle spasms in the face, jaw, pharynx, and tongue, causing difficulty in jaw closing or opening and interfering with fluid and food intake and speech; muscles in the neck, larynx and respiratory system may be involved in severe cases. Temporomandibular joint dislocation may occur. Spasticity due to spinal cord injury, baclofen (Lioresal) is frequently the drug of choice 1. It reduces the hypertonia and flexor spasm by potentiating the presynaptic inhibitory effect of GABA. Sedation, Confusion, and hallucination may be seen as a side effect. 2 Myofascial Pain Syndrome: is characterized by acute or chronic regional pain associated with localized nodular masses known as trigger points. Spasmodic Dysphonia (laryngeal dystonia): is a centrally mediated neurologic disorder characterized by action-induced spasms of the vocal cords, leading to choked, constrained vocalizations interrupted frequently by voiceless pauses. This condition may occur alone or in combination with other dystonic movements. The adductor type of this condition is characterized by forceful, involuntary closure of the vocal cords, causing strained or strangled, hoarse voice; the abductor type which is less common causes breathy, whispery voice. Some patients have combinations of both types. Spasticity (muscle spasm): an abnormal increase in muscle tone. It can be caused by some types of damage to the nerve pathways regulating muscles and can lead to incoordination, loss of function, pain, and permanent muscle shortening, or contracture. Possible causes include anoxia, toxic and metabolic encephalopathies, localized tumors, cysts, trauma, brain injuries, vascular disease, multiple sclerosis, and inflammatory or degenerative disease. To analyze spasticity and its effect, electromyography (EMG) can be use to verify involvement of the muscles. In assessing limb function, detailed questions regarding functional status for activities of daily living (ADLs) and mobility are needed. References: 1. Ditunno JF, Formal CS. Chronic Spinal Cord injury. N Engl J Med. 1994;220:550-6 2. Fried GW, Fried KM. Spinal cord injury and use of botulinum toxin in reducing spasticity. Phys Med Rehabil Clin N Am. 14(2003):901-10. 3. International Foundation for Functional Gastrointestinal Disorder. Available at www.aboutibs.org. Accessed on 1/10/07. Last updated on 5/1/05. 4. Health on the Net Foundation. Available at www.hon.ch. Accessed on 1/10/07. Last updated 11/10/06. 5. Compendia: AFHS 2007;USPDI 2007;Micromedex accessed online 2007 6. Package labeling Myobloc. Solstice Neurosciences. 11/04; Package labeling. Botox. Allergen, Inc. 10/06. 7. Factor S. Adler C. Brashear A. et al. Practical considerations for the clinical use of botulinum toxin type B. A self-study continuing medical education activity. We Move. Worldwide Education and Awareness for Movement Disorders. Release date 2/02. 8. Blitzer A. Botulinum Toxin A and B: A comparative dosing study for spasmodic dysphonia. Otolaryngology 2005; 133:836-838. 9. Costa J. Borges A. Espirito-Santo C. Ferreira J. Coelho M. Moore P. Sampaio C. Botulinum toxin A versus botulinum toxin type B for cervical dystonia. The Cochrane Library 2006; Volume (2). 10. Thakker M. Rubin P. Pharmacology and clinical applications of botulinum toxins A and B. International Ophthalmology Clinics; Issue 3: Vol (44): p147-163. 11. Barnes M. Botulinum toxin-mechanisms of action and clinical use in spasticity. J Rehabil Med 2003; Suppl. 41: 56-59. 12. Cheng. Christine M. Chen. Jennifer S. Patel. Rosalie P. Unlabeled uses of botulinum toxins: A review, part 2. AM J Health, Vol 63(3). Feb 1,2006.225-232. 13. Cheng. Christine M. Jennifer S. Chen. Rosalie P. Patel. Unlabeled uses of botulinium toxins: A review, part 1. AM J Health, Vol 63(3). Jan 15,2006.145-152. 14. Bhidayasiri R. Truong D. Expanding use of botulinium toxin. Journal of the Neurological Sciences 2005; 235:1-9. 15. Boyd R. Hays R. Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systemic review. European Journal of Neurology 2001;8(Supply5): 1-20. 16. Koman A. Smith B. Shilt J. Cerebral palsy. Vol 363: May15, 2004:1619-1631. 17. Dodick D. Blumenfeld A. Silberstein S. Botulinum neurotoxin for the treatment of migrane and other primary headache disorders. Clinical in Dermatology 2004; 22:76-81. 18. Sheean G. Botulinum toxin treatment of adult spasticity. Drug Safety 2006;29(1):31-48. 19. Watts C. Nye C. Whurr R. Botulinum toxin for treating spasmodic dysphonia(laryngeal dystonia): a systemic Cochrane review. Clinical Rehabilitation 2006; 20:112-122. 20. Yamauchi P. Lowe N. Botulinium toxin types A and B: Comparison of efficacy, duration and dose-ranging studies for the treatment of facial rhytides and hyperhidrosis. Clinics in Dermatology 2004; 22:34-39. 21. Dressler D. Saberi F. Benecke R. Botulinum toxin type B for the treatment of axillar hyperhidrosis. Journal of Neurology 2002; 249:1729-1732. 22. Gage J. Novacheck T. An update on the treatment of gait problems in cerebral palsy. Journal of Pediatric Orthopaedics 2001; 10:265-274. 23. Dutton J. White J. Richard M. Myobloc for the treatment of benign essential blepharospasm in the patients refractory to botox. Opthalmic Plastic and Reconstructive Surgery 2006; Vol.22, No. 3, pp 173-177. 24. Contarino MF. Pompili M. Tittoto P. Vanacore N. et al. Botulinum toxin-b ultra sound-guided injections for sialorrhea in amyotrophic lateral sclerosis and Parkinson s disease. Parkinsonism & Related Disorders.2006.05.05 25. Ondo WG. Hunter C. Moore W. A double-blind, placebo controlled trial of botulinum toxin type-b for sialorrhea in Parkinson s disease. Neurology.2004;62:37-40. 26. Rachette BA. Good L. Sagitto S. Perlmutter JS. Botulinum toxin type-b reduced sialorrhea in Parkinsonism. Movement Disorders. 2003;18:1059-1061.

27. Berman B, Seeverger L, Kumar R. Long term safety and efficacy, dosing and development of resistance with botulinum toxin type B in cervical dystonia. Mov Disorders 2005; 20(2): 233-7 28. Brashear A, Lew MF, Dykstra DD, et al.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 1999 October 22;53(7):1439-45. 29. Brin MF, Lew MF, Adler CH, et al.: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 1999 October 22;53(7): 1431-8. 30. Comella CL, Jankovic J.: Comparison of botulinum toxin serotype A and B for the treatment of cervical dystonia. Neurology 2005 November 65(9): 1423-29. 31. Factor SA, Molho ES, Evans S, Reustel PJ. Efficacy and safety of repeated doses of botulinum type B in type A resistant and responsive cervical dystonia. Mov disorders 2005; 20(9): 1152-60. 32. Fahn S edited by Jankovic J. Chapter 8 Dystonia. Therapy with Botulinum Toxin Textbook. 33. Lew MF. Botulinum toxin type B. An effective treatment for alleviating pain associated with cervical dystonia. Journal of Back and Musculoskeletal Rehabilitation 2002; 16:3-9. 34. Leong M, Royal M. A randomized double-blind study to compare the efficacy and safety of Neurobloc (MYOBLOC) botulinum toxin type-b with Botox (botulinum toxin type-a) in toxin-naïve subjects with cervical dystonia. Poster presentation at International Conference 2005 Basic and therapeutic aspects of botulinum and tetanus toxins, Denver, CO, June 23-25, 2005 (under auspices of the Neurotoxicity Society). 35. Struck LK. Botulinum toxin type B (MYOBLOC) at doses greater than 10,000 units for the treatment of cervical dystonia: two case studies. Movement Disorders 2002; 17 (supp5). Poster Presentation at the 7 th International Congress of Parkinson s Disease and Movement Disorders in Miami, FL Nov 10-14, 2002. 36. Sunter W, Leong M, Royal M. The cervical dystonia subset of the mind registry database. Poster Presentation international conference 2005 basic therapeutic aspects of botulinum and tetanus toxins, Denver, CO, June 23-25, 2005 (under auspices of the Neurotoxicity Society). 37. Bell K, Williams F. Use of Botulinum Toxin type A and type B for spasticity in upper an lower limbs. Phys ed rehabil Clin N Am. (2003) 14: 821-35. 38. Brashear A, McAfee AL, Kuhn ER, Ambrosius WT. Treatment with botulinum toxin type B for upper-limb spasticity. Arch Phys Med Rehabil 2003:84(1): 103=07. 39. Brashear A, McAfee AL, Kuhn ER, Fyffe J. Botulinum toxin type B in upper-limb poststroke spasticity: a double-bind placebo controlled trial. Arch Phys Med Rehabil 2004;85(5): 705-09. 40. Brinke M. Combined treatment of spastic dysbalance of the hand with botulinum toxin type B followed by constrained-induced movement therapy. J Neurol Rehabil 2002;8(6):311-14. 41. Fried GW, Fried KM. Spinal cord injury and use of botulinum toxin in reducing spasticity. Phys Med Rehabil Clin N Am. (2003) 14:901-10. 42. McGuire J. Effective use of chemodenervation and chemical neurolysis on the management of poststroke spasticity. Topics in Stroke Rehab 2001; 8(1): 47-55. 43. O Brien CF. Treatment of spasticity with botulinum toxin. Clin J Pain 2002;Dec 18 (supp6): 182-90. 44. Oechsner M. Treatment of hip adductor spasticity with botulinum toxin type B. Nervenarzt 2002;73(12): 1179-82 45. Dysktra D. Botulinum toxin type B for gait and ankle-foot orthosis fit improvement in post-cva spasticity. Archives of Pharmacology 2002; June 365 (supp2): R18. Poster Presentation at toxins, June 8-11, 2002. 46. Fried Gw. Botulinum toxin type B improves spasticity and function in patients with quadriplegia. Archives of Pharmacology 2002; June 365 (supp2): R20 poster presented at toxins, June 8-11, 2002. 47. Fried GW. Botulinum toxin type B improves pain and function in patients with spasticity due to quadriplegia. Archive of Pharmacology 2002; June 2002 (supp20): R42 poster presented at toxins, June 8-11, 2002. 48. Heavner JE, Day MD, Shah R, Raj PP, Racz GB. Demographics and Doses of MYOBLOC (Botulinum toxin type B) used to treat pain and spasticity from patient registry. Abstract presented at Annual Scientific Meeting of the American Pain Soceity. Chicago, IL. March 20-23, 2003. 49. Hecht JS, Preston L, Harriman, MCPhee S. Effects of botulinum toxin type B on shoulder pain, hypertoina, and functioning adults with spastic hemiparesis. Arch Phys Med and Rehabil 2002; Nov. 83(11). Poster presented at 63 rd Annaul Assembly of the American Academy of Physical Medicine and Rehabilitation. Nov. 21-24, 2002. 50. Jayasooriya S, Francisco GE, Healy W. Early experience with the use of MYOBLOC )botulinum toxin type B for the treatment of upper limb spasticity hypertonia. Arch Phys Med Rehab 2002; Nov. 83(11); 1677. Poster presented at 63 rd Annual Assembly of the American Academy of Physical Medicine and Rehabilitation, Nov. 21-24, 2002. 51. O Brien C, Mancini F. Botulinum toxin type B (MYOBLOC) for limb spasticity. Archives of Pharmacology 2002; June 365 (supp2): R32 poster presentation at toxins, June 8-11, 2002. 52. Smith H, Dubin A, Tang J. Evaluation of botulinum toxin type B for a patient with painful muscle spasms. Archives of pharmacology2002; June 365 (supp2): R42. Poster presented at toxins June 8-11, 2002; and 21 st Annual Scientific Meeting of the American Pain Society. March 14-17, 2002. 53. Adler CH, Bansberg SF, Krein-Jones, Hentz JG. Safety and efficacy of botulinum toxin type B (MYOBLOC) in adductor spasmodic dysphonia. Movment Disorders 2004; Vol. 3, Issue 9: 1075-79. 54. Gutinas-Lichius O. Injection of botulinum toxin type B for the treatment of otolaryngology patients with secondary treatment failure of botulinum toxin type A. Laryngoscope 2003 April; 113(4): 743-45. 55. Sataloff RT, Herman-Ackah YD, Simpson LL, Park JB, Zwislewski A, Sokolow C, Mandel S. Botulinum toxin type B for the treatment of spasmodic dysphonia: a case report. Journal of Voice 2002; Sept 16(3): 422-24. 56. Adler CH, Bansberg SF, Krein-Jones K, Lind M, Hentz JG. Safety and efficacy of botulinum toxin type B (MYOBLOC) in adductor spasmodic dysphonia. Movement Disorders 2002. 17. (supp5): S277. Poster presentation at 7 th international congress of Parkinson s disease and movement disorders. Miami Fl. Nov 10-14, 2002. 57. Baumann L, Slezinger A, Halem M, et al. Pilot study on the safety and efficacy of MYOBLOC (botulinum toxin type B) for the treatment of axillary hyperhidrosis. Int J Dermatol 2005 May; 44(5): 418-24. 58. Baymann L, Slezinger, Halem M, et al. Double-blind, randomized, placebo-controlled pilot study of the safety and efficacy of MYOBLOC (botulinum toxin type B) for the treatment of palmar hyperhidrosis. Dermatol Surg 2005 March; 31(3): 263-70. 59. Baumann L, Halem M. Botulinum toxin-b and the management of hyperhidrosis. Clinics and Dermatology 2004; 22: 60-65. 60. Dressler D, Saberi FA, Benecke R. Botulinum toxin type B for the treatment of axillar hyperhidrosis. J Neurol. 2002; 249: 1729-32. 61. Glogau RG. Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes. Clin J of Pain 2002; 18(supp6): 191-97. 62. Hecht MJ, Birklein F, Winterholler M. Successful treatment of axillary hyperhidrosis with very low doses of botulinum toxin B: A pilot study. Arch Dermatol Res 2004 February; 295(8-9): 318-19. 63. Nelson L, Bachoo P, Holmes J. Botulinum toxin type-b; a new therapy for axillary hyperhidrosis. Br J Plast Surg 2005 March; 58(2): 228-32. 64. Winterholler M, Eisenbarth G, Erbguth, Briklein F. A systematic analysis of dose related local antihydrotic effects of NeuroBloc/MYOBLOC (botulinum toxin type-b) injected as measured sudometry, Movement Disorders 2002; 17(supp5): S41. Poster presenetation toxins June 8-11, 2002.

65. Colosimo C, Chianese M, Giovannelli M, Contarino MF, Bentivogilo AR. Botulinum toxin type B in blepharospasm and hemifacial spasm (Letter) J Neurol Neurosurg Psychiatry 2003; 74: 687. 66. Samanta JE, Stacy MA. Efficacy of botulinum toxin type-b (MYOBLOC) in case of hemifacial spasm. Movement Disorders 2002; 17(supp): S286. Poster presentation at toxins, Hanover, Germany June 8-11, 2002. 67. Samanta JE, Stacy MA. Efficacy of MYOBLOC (botulinum toxin type B) for the treatment of blepharospasm: report of two cases. Arch of Pharmacology2002; June 365(supp2): R16. Poster presentation at toxins, Hanover Germany June 8-11, 2002. 68. Struck LK. Botulinum toxin type-b (MYOBLOC) hot hemifacial spasm: report of three cases. Arch of Pharmacology 2002; June 365(supp2). Poster presentation at toxins June 8-11, 2002. 69. Struck LK. Botulinum toxin type-b (MYOBLOC) for the treatment of hemifacial spasm and blepharospasm. Movement Disorders 2002; 17 (supp5): S278. Poster presentation at 7 th International Congress of Parkinson s Disease and Movement Disorders, Miami, FL. Nov 10-14, 2002. 70. Arezzo J. Possible mechanisms for the effect of botulinum toxin on pain. Clinic J of Pain; Vol 18, No. 6 Supplemental 2002; S125-S131. 71. Argoff CE. A focused review of the use of botulinum toxins for neuropathic pain. The Clinical J of Pain 2002; 18; S177 72. Difazio M, Jabbari B. A focused review of the use of botulium toxins for low back pain. The Clinical J of Pain 2002; 18: S155 73. Fishman LM, Konnoth C, Rozner B. Botulinum neurotoxin type-b and physical therapy in the treatment of piriformis syndrome: A dose finding study. Am J Med Rehabilitation 2003; 83: 42-50. 74. Freund BJ, Schwartz M. Use of botulinum toxin in chronic whiplash-associated disorder. Clinical J of Pain 2002; 18: S163. 75. Lew MF. Review of FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. Clinical J of Pain 2002; 18: S142. 76. Lew MF. Botulinum toxin type-b: an effective treatment for alleviating pain associated with cervical dystonia. J of back and musculoskeletal rehab; 16 (2002): 3-9. 77. Smith HS, Audette, J, Royal MA. Botulinum toxin in pain management of soft tissue syndromes. Clinical J of Pain 2002; 18: S147-S154. 78. Heavner J, Leong M, Royal M. The mind registry: An observational database of patients treated with botulinum toxin type-b (MYOBLOC)- pain subset of the database. Poster presentation international conference 2005 basic therapeutic aspects of botulinum and tetanus toxin, Denver, CO, June 23-25, 2005 (under auspices of the Nuerotoxicity Society). 79. Ibrahim M, Frank E. Botulinum toxin type-b (MYOBLOC) for axial component of neuropathic pain: A case report. J of Pain 2002; Vol 3 Issue 2 (supp1): 13-16. Abstract presentation 21 st Annual Scientific Meeting American Pain Society, Baltimore, MD March 14-17, 2002. 80. Neiman RB. Botulinum toxin type -B (MYOBLOC) in the treatment of myofascial pain conditions. Abstract presented at Annual Scientific Meeting of the American Pain Society. Chicago, IL March 20-23, 2003. 81. Nalamachu S. Treatment with botulinum toxin type-b (MYOBLOC) injections in three patients with myofascial pain. Pain Medicine. 2002;3(2):182. Poster presentation 18 th annual meeting American Academy of Pain Medicine. San Francisco, CA. Feb 26-March 2, 2002. 82. Rhoades PN. Evaluation of botulinum toxin type-b (MYOBLOC) for myofascial pain: results from a preliminary patient survey. Pain Management. 2002;3(2)178. Poster presentation 18 th annual meeting American Academy of Pain Medicine. San Francisco, CA. Feb 26-March 2, 2002. 83. Royal MA. Adams D. Jenson M. Botulinum toxin type-b (MYOBLOC) in the treatment of refractory lumbar myofascial pain. Archives of Physical Medicine and Rehabilitation. 2002;83(11):1670. Poster presentation Toxins June 8-11, 2002 and 63 rd annual assembly of American Academy of Physical Medicine and Rehabilitation. November 21-24, 2002. 84. Smith H. Botulinum toxin type B injection for a patient with myofascial pain. Archives of Pharmacology. 2002;365(supp 2):R41 and Pain Medicine 2002;3(2):174.Poster presentation at Toxins June 8-11, 2002. 85. Taqi D. Gunyea I. Bhakta B. Movva V. Ward S. et al. Botulinum toxin type B(MYOBLOC) in the treatment of refractory myofascial pain. Pain Medicine. 2002;3(2):174.Poster presentation and 63 rd annual assembly of American Academy of Physical Medicine and Rehabilitation. November 21-24, 2002 and 21 st annual Scientific meeting of the American Pain Society, March 11-14, 2002. 86. Argoff CE. The use of botulinum toxins for chronic pain and headache. Current Treatment Options in Neurology. 2003;5:483-492. 87. Fadeyi MO. Adams QM. Uses of botulinum toxin type-b for migraine and tension type headaches. American Journal of Health System Pharmacists. 2002;13(3):79-85. 88. Gokani T. Robbins L. Botulinum toxin:efficacy in migraine, tension-type and cluster headaches. American Journal of Pain Management. 2002;13(3):79-85. 89. Loder E. Biondi D. Use of botulinum toxin for chronic headache: A focused review: Clinical Journal of Pain. 2002;18(supp 6):S169-S176. 90. Argoff Ce. Successful treatment of chronic daily headache with botulinum toxin type-b(myobloc).archives of Pharmacology. 2002;365(supp 2): R11: Poster presentation at Toxins June 8-11, 2002 and 21 st annual Scientific meeting of the American Pain Society, March 11-14, 2002. 91. Gwynn MW. English J. Baker T. Double-blind, placebo controlled study of MYOBLOC (botulinum toxin type-b) for preventing chronic headache. Poster presentation American Academy of Neurology 55 th annual meeting. Honolulu, HI. March 29-April 5, 2003. 92. Krusz JC. Intradermal botulinum toxin type-b for migraine of cervical origin. Abstract presentation at annual scientific meeting of American Pain Society. Chicago, IL. March 20-23, 2003. 93. Lake AE. Saper JR. Botulinu toxin type-b for migraine prophylaxis. A 4-month, open-label, prospective outcome study. Abstract presentation at annual scientific meeting of American Pain Society. Chicago, IL. March 20-23, 2003. 94. Opedia CL. Open-label study of MYOBLOC (botulinum toxin type-b) in the treatment of patients with transformed migraine headaches. Poster presentation at Toxins June 8-11, 2002 and Annual Scientific meeting American Pain Society March 14-17, 2002.Open-label study of MYOBLOC (botulinum toxin type-b) in the treatment of patient with post-whiplash headache. Poster presentations at Toxins June 8-11, 2002. both in Archives of Pharmacology. 2002;365(supp 2). 95. Gooch JL. Patton CP. Combining botulinum toxin with phenol to manage spasticity in children. Archives of Physical Medicine and Rehabilitiation. 2004;85(7):1121-1124. 96. Schwerin A. Botulinum toxin type-b treatment in children with spastic movement disorders: A pilot study. Neurology. 2004;31(2):109-113. 97. BeDell K. Plant K. Focier S. A case report of the use of botulinum toxin type-b for the treatment of spasticity in a child with severe spastic quadriplegic cerebral palsy. Archives of Physical Medicine and Rehabilitation. 2002;83(11):1675. Poster presentation at 63 rd annual assembly of American Academy of Physical Medicine and Rehabilitation. November 21-24, 2002. 98. Royal M. Leong M. A review of pediatric adverse events associated with botulinum toxin type-b (MYOBLOC). Poster presentation International conference 2005 basic and therapeutic aspects of botulinum and tetanus toxins. Denver CO, June 23-25, 2005 (under auspices of Neurotoxicity Society). 99. Walke K, 8-Wolf E. The use of botulinum toxin type-b in the pediatric population. Archives of Physical Medicine and Rehabilitation. 2002;83(11):163. Poster presentation at 63 rd annual assembly of American Academy of Physical Medicine and Rehabilitation. November 21-24, 2002. 100. Turk-Gonzales M. Odderson IR. Quantitiative reductin of saliva production with botulinum toxin type-b injections into the salivary glands. Neurorehabilitation Neural Repair. 2005:19(1):58-61. 101. Wright E. Botulinum toxin type-b for treatment of pediatric sialorrhea. Archives of Physical Medicine and Rehabilitation. 2002;83(11):1673. Poster presentation 63 rd annual assembly American Academy of Physical Medicine and Rehabilitation, November 21-24, 2002.

102. Dykstra DD. Et al. Treatment of overactive bladder with botulinum toxin type-b: a pilot study. International Urogynocol J Pelvic Floor Dysfunction.2003;14:424-426. 103. Dykstra DD. Botulinum toxin in the management of bowel and bladder function in spinal cord injury and other neurologic disorders. Phys Med Rehabilitation Clin N. Am. 2003;14:793-804. 104. Dykstra DD. Pryor J. Goldish G. Use of botulinum toxin type-b for the treatment of detrusor hyperreflexia in a patient with Multiple Sclerosis: a case report. Archives of Physical Medicine and Rehabilitation. 2003;84:1399-1400. 105. Stacy MA. Treatment of writer s cramp (hand dystonia) with MYOBLOC (botulunum toxin type B) Movement Disorders 2002 (supp 5) and Archives of Pharmacology 2002; June 365 (supp 2):R43. Poster presentation at Toxins, Hanover, Germany, June 8-11, 2002 and 7 th International Congress of Parkinson s Disease and Movement Disorders, Miami, FL, Novemeber 10-14, 2002. 106. Critchfield J. Considering the immune response of botulinum toxin. Clinical Journal of Pain. 2002;18:S133-S141. 107. Freund B. Schwrtz M. Use of toxin in chronic Whiplash-associated disorder. Clinical Journal of Pain. 2002;vol 18 No 6:S163-S168. 108. Gollump S. Weighing the options in Neurotoxin therapy. Practical Neurology. 2002;February 1(2):42-45. 109. Schwartz M. Freund B. Treatment of temporomandibular disorders with botulinum toxin. Clinical Journal of Pain. 2002;Vol18 No 6 (supp): S198-S203. 110. Seltre PF. Therapeutic use of botulinum toxins background and history. Clinical Journal of Pain. 2002;18S119-S124. 111. Carpentiar B. Leong M. Case Report: Treatment of post-mastecomy syndrome with botulinum toxin. Poster presentation International conference 2005 basic and therapeutic aspects of botulinum and tetanus toxins. Denver CO, June 23-25, 2005 (under auspices of Neurotoxicity Society). 112. Royal M. Towey BD. O Brien C. The MIND registry: capturing the clinical uses of MYOBLOC (botulinum toxintype-b). Movements Disorders. 2002;17(supp 5): S307. 113. Setler PF. Burke D. Callaway J. Wang C. Stability of MYOBLOC (botulinum toxin type-b) in preserved saline. Archives of Pharmacology.2002;365(supp 2). Poster presentation at toxins June 8-11, 2002. 114. Package Labeling Botox, Allergan Pharmaceuticals Ireland. 01/05; Package labeling. Botox Cosmetic (Botulinum Toxin Type A). Allergen, Inc. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician review must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA CELEBREX (celecoxib) Capsule: 50mg, 100mg, 200mg 400mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: ANTICOAGULANT THERAPY: Diagnosis of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or ankylosing spondylitis and Current therapy with anticoagulant therapy such as warfarin If the above conditions are met, the request will be approved with a 3-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. Re-evaluation of continued warfarin therapy will be assessed at 3-month intervals for renewal. DOCUMENTED GASTROINTESTINAL DISEASE (GERD, Erosive Esophagitis, Barretts Esophagus, Zollinger Ellison Disease): Diagnosis of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or ankylosing spondylitis and Documented gastrointestinal disease of the following conditions: gastroesophageal reflux disease, erosive esophagitis, Barretts esophagus, or Zollinger Ellison disease), currently taking either a proton pump inhibitor or an H2 receptor antagonist. If the above conditions are met, the request will be approved with a 6-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. NSAID THERAPY FAILURE: Diagnosis of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or ankylosing spondylitis and Documented trial and failure with therapeutic prescription doses or intolerance to at least two formulary nonsteroidal anti-inflammatory drugs (NSAIDs). If the above conditions are met, the request will be approved with a 6-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FAMILIAL ADENOMATOUS POLYPOSIS (FAP): Diagnosis of familial adenomatous polyposis (FAP) If the above conditions are met, the request will be approved with a 6-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PRIMARY DYSMENORRHEA: Premenopausal female patient and Diagnosis of primary dysmenorrhea and Documented trial and failure with therapeutic prescription doses or intolerance to at least two formulary nonsteroidal anti-inflammatory drugs (NSAIDs). If the above conditions are met, the request will be approved with a 5-day duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. ACUTE PAIN: Diagnosis of acute pain and Documented trial and failure with therapeutic prescription doses or intolerance to at least two formulary nonsteroidal anti-inflammatory drugs (NSAIDs). If the above conditions are met, the request will be approved with a 5 day duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: For relief of the signs and symptoms of osteoarthritis (OA). For relief of signs and symptoms of rheumatoid arthritis (RA) in adults. For relief of signs and symptoms of juvenile rheumatoid arthritis (JRA) in patients 2 years and older. For relief of signs and symptoms of ankylosing spondylitis (AS). For the management of acute pain in adults. For treatment of primary dysmenorrhea.

DOSAGE AND ADMINISTRATION: OA: Recommended dosage is 200 mg/day administered as a single dose or as 100 mg twice a day. RA: Recommended dosage is 100 to 200 mg twice a day. JRA: Recommended dosage is 50mg twice daily for pediatric patients > 2 years old and weigh 10 kg - 25 kg or is 100mg twice daily for pediatric patients > 2 years old and weigh >25 kg. AS: Recommended dosage is 200mg administered as a single dose or as 100mg twice a day. If no effect is observed after 6 weeks, a trial of 400mg daily may be worthwhile. If no effect is observed after 6 weeks on 400mg daily, a response is not likely and consideration should be given to alternate treatment options. Acute Pain: Recommended dose is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed. Primary Dysmenorrhea: Recommended dose is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed. Hepatic impairment: The daily recommended dose of celecoxib in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by approximately 50%. The use of celecoxib in patients with severe hepatic impairment is not recommended. Patients who are known or suspected CYP2C9 poor metabolizers: Consider alternative management for JRA. Consider 50% reduction in dose for all other indications. BOXED WARNING: Celecoxib may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke which can be fatal. The drug is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Celecoxib may also cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. REFERENCES: 1. Deeks JJ; Smith LA; Bradley MD. Efficacy, Tolerability, and Upper Gastrointestinal Safety of Celecoxib for Treatment of Osteoarthritis and Rheumatoid Arthritis: Systematic Review of Randomized Controlled Trials. BMJ. 2002 Sep 21;325(7365):619. 2. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the Management of Rheumatoid Arthritis. 2002 Update. Arthritis and Rheumatism Vol 46. No 2. February 2002. pp 328-346 3. Celebrex Product Information. G.D. Searle LLC. January 2011. 4. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 5. Braun, J. et al. First Update of the International ASAS Consensus Statement for the Use of Anti-TNF Agents in Patients with Ankylosing Spondylitis. Ann Rheum Dis. 2006; 65:316-320. 6. Agency for Healthcare Research and Quality (AHRQ). Comparative Effectiveness and Safety of Analgesics for Osteoarthritis. 2006 September. Available from www.ahrq.gov. Accessed March 2007. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

CEREDASE (alglucerase): 80-u/ml IV injection PA CRITERIA FOR APPROVAL: The patient has the diagnosis of Type I Gaucher s disease. AND The patient is being prescribed the appropriate dose. AND TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FORMULARY STATUS: Non-formulary There is documentation that the patient has Gaucher s disease severe enough to result in one of the following: moderate to severe anemia, thrombocytopenia with bleeding tendency, bone disease, and/or significant hepatomegaly or splenomegaly. If all of the above conditions are met, the request will be approved with a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Ceredase (alglucerase injection) is indicated for use as long-term enzyme replacement therapy for patients with a confirmed diagnosis of Type 1 Gaucher s disease who exhibit signs and symptoms that are severe enough to result in one or more of the following conditions: -moderate-to-severe anemia -thrombocytopenia with bleeding tendency -bone disease -significant hepatomegaly or splenomegaly DOSAGE AND ADMINISTRATION: Initial dosage may be as little as 2.5 units/kg 3 times a week up to as much as 60 units/kg every 1 to 4 weeks as an IV infusion. Doses should be individualized. Progressive reduction can be made at 3-6 months intervals. REFERENCES: 1. Gaucher s Disease. [resource on World Wide Web] URL: http://www.gaucher.org.uk/living.htm 2. Ceredase prescribing information. Genzyme Corporation - 500 Kendall Square Cambridge, MA 02139 October 2004. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA CIPRODEX (0.3% ciprofloxacin, 0.1% dexamethasone) Otic Suspension: 7.5mL FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Documented trial and failure, contraindication, or intolerance to ofloxacin otic drops. OR Prescribing provider is an ear, eye, nose and throat (EENT) physician. If the above conditions are met, the request will be approved with a 3 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Ciprodex is indicated for acute otitis externa and otitis media in patients with tympanostomy tubes. DOSAGE AND ADMINISTRATION: Otitis Externa: Children 6 months and older- 4 drops into affected ear twice daily for 7 days. Otitis Media: Children 6 months and older- 4 drops into affected ear twice daily for 7 days. REFERENCES: 1. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Ciprodex Product Information. Alcon Laboratories, Inc. September 2010. 3. Floxin Product Information. Daiichi-Sankyo. November 2006. 4. Rosenfeld RM et al. American Academy of Otolaryngology Head and Neck Surgery Foundation Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg 2006 Apr; 134(4 Suppl): S4-23. 5. Sander R. et al. Otitis Externa: A Practical Guide to Treatment and Prevention. American Family Physician. 2001; 63927-36,941-2. 6. Subcommittee on management of acute Otitis Media. Diagnosis and management of Acute Otitis Media. Pediatrics. May 2004;113(1451-65). Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA COLCRYS (colchicine) Tablet: 0.6 mg STATUS Non-Preferred PA CRITERIA FOR APPROVAL Acute gout attack: Is 17 years of age or older Has a documented history of therapeutic failure, intolerance, or contraindication to the following at appropriate doses and frequencies for the treatment of gout: NSAIDs or COX-2 Inhibitors AND Intra-articular or systemic corticosteroids If the above conditions are met, the request will be approved with up to three 0.6 mg tablets (total 1.8mg) for up to a 2 week duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. Chronic gout: Is 17 years of age or older Is being prescribed Colcrys in combination with a uric acid lowering medication (such as allopurinol, probenecid or Uloric) recently started for the prophylaxis of gout attacks. The uric acid lowering medication must be titrated based on renal function to target uric acid level, or to a maximum allopurinol dose of 800mg/day. If the above conditions are met, the request will be approved for a 6 month duration; if the above conditions are not met, the request will be to a Pharmacist for medical necessity review. Familial Mediterranean Fever (FMF): is 4 years of age or older If the above condition is met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS For the prophylaxis and the treatment of acute gout flares when taken at the first sign of a flare. For the treatment of familial Mediterranean fever in adults and children 4 years of age and older. DOSAGE AND ADMINISTRATION FDA-approved uses: Familial Mediterranean fever: Usual dosage: 1.2 mg to 2.4 mg daily in 1 or 2 divided doses. Dosage adjustment: Increase as needed in increments of 0.3 mg/day to a maximum recommended daily dose to control disease and as tolerated. If intolerable adverse effects develop, the dosage should be decreased in increments of 0.3 mg/day. Prophylaxis of gout flares: Usual dosage: 0.6 mg once or twice daily. Maximum dose: 1.2 mg/day.

Treatment of gout flares: Usual dosage: 1.2mg at the first sign of flare followed by 0.6mg one hour later. *If also taking colchicine for gout prophylaxis, wait 12 hours after last treatment dose, then resume prophylaxis Maximum dose: 1.8mg over a one hour period REFERENCES 1. Treatment of Acute Gout. UpToDate ONLINE. Accessed December 16, 2012. 2. Prevention of Recurrent Gout. UpToDate ONLINE. Accessed December 16, 2012. 3. Facts and Comparisons, St. Louis, 2012 efacts CliniSphere Version ISBN 1-57439-036-8. 4. Colcrys [package insert]. Philadelphia, PA: AR Scientific; December 2009. 5. Kelly JC. Gout guidelines from ACR include new drugs, diet. Medscape Medical News. Available at http://www.medscape.com/viewarticle/771945. Accessed October 12, 2012. 6. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). Oct 2012;64(10):1431-46. [Medline]. Revision/Review Date: 2/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA DANOCRINE (danazol) Capsule: 50mg, 100mg, 200mg FORMULARY STATUS: Formulary (generic) PA CRITERIA FOR APPROVAL: ENDOMETRIOSIS: Diagnosis of endometriosis. AND Documented trial and failure, intolerance or documented medical reason for not using first line therapy of oral contraceptive therapy. AND Prescribing physician is a gynecologist. If the above conditions are met, the request will be approved with a 6 month duration for generic medication; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FIBROCYSTIC BREAST PAIN: Diagnosis of fibrocystic breast disease. AND Documented trial and failure, intolerance or documented medical reason for not using first line therapy of analgesics including acetaminophen and NSAIDs. AND Prescribing physician is a gynecologist. If the above conditions are met, the request will be approved with a 6 month duration for generic medication; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. HEREDITARY ANGIOEDEMA: Diagnosis of hereditary angioedema. If the above condition is met, the request will approved with a 6 month duration for generic medication; if the above condition is not met, the request will be referred to Medical Director for medical necessity review. FDA INDICATIONS: Endometriosis: For the treatment of endometriosis amenable to hormonal management. Fibrocystic Breast Disease: Danazol is usually effective in decreasing nodularity, pain, and tenderness, but it considerably alters hormone levels. Recurrence of symptoms is very common after cessation of therapy. Hereditary Angioedema: For the prevention of attacks of angioedema (eg, cutaneous, abdominal, laryngeal) in males and females. DOSAGE AND ADMINISTRATION: Endometriosis: Begin therapy during menstruation or make sure the patient is not pregnant. In moderate-to-severe disease, or in patients infertile because of endometriosis, administer 800 mg/day in 2 divided doses to best achieve amenorrhea and rapid response to painful symptoms. Downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon response. Initially, for mild cases, give 200 to 400 mg in 2 divided doses. Individualize dosage. Continue therapy uninterrupted for 3 to 6 months; may extend to 9 months. If symptoms recur after termination, treatment can be reinstituted. Fibrocystic Breast Disease: Begin therapy during menstruation or make sure patient is not pregnant. Dosage ranges from 100 to 400 mg/day in 2 divided doses. A non-hormonal method of contraception is recommended when danazol is administered at this dose because ovulation may not be suppressed. Breast pain and tenderness are usually relieved by the first month and

eliminated in 2 to 3 months; elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular or irregular menstrual patterns and amenorrhea each occur in» 1/3 of patients treated with >100 mg doses. Approximately 50% of patients may have recurring symptoms within 1 year; treatment may be reinstituted. Hereditary Angioedema: Individualize dosage. Recommended starting dose is 200 mg 2 or 3 times/day. After a favorable initial response, determine continuing dosage by decreasing the dosage by < 50% at intervals of >1 to 3 months if frequency of attacks prior to treatment dictates. If an attack occurs, increase dosage by <200 mg/day. During the dose-adjusting phase, monitor response closely, particularly if patient has a history of airway involvement. BLACK BOX WARNING: Use of danazol is contraindicated in patients with undiagnosed abnormal genital bleeding; markedly impaired hepatic, renal, or cardiac function. Use of danazol in pregnancy and during lactation is contraindicated. A sensitive test (eg, beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally, a nonhormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking danazol, discontinue administration of the drug and apprise the patient of the potential risk to the fetus. Use of danazol is contraindicated in patients with porphyria. Danazol can induce aminolevulinate acid (ALA) synthetase activity and hence porphyrin metabolism. Thromboembolism, thrombotic and thrombophlebitic events, including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported. Experience with long-term therapy with danazol is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially lifethreatening intra-abdominal hemorrhage. Therefore, alert the physician to this possibility. Attempts should be made to determine the lowest dose that will provide adequate protection. Danazol has been associated with several cases of benign intracranial hypertension also known as pseudotumor cerebri. Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Screen patients with these symptoms for papilledema and, if present, advise the patients to discontinue danazol immediately and refer them to a neurologist for further diagnosis and care. REFERENCES: 1. Winkel CR. Evaluation and Management of Women with Endometriosis. Obstet Gynecol 2003;102(2):397-408 2. Smith RL, Pruthi S, Fitzpatrick LA. Evaluation and management of breast pain. Mayo Clin Proc 2004;79(3):353-372 3. Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT. Endometriosis and its treatment with Danazol or Lupron in relation to ovarian cancer. Clin Cancer Res. 2003;9(14):5142-5144 4. Duckitt K. Menorrhagia. Clin Evid 2002 Jun;(7):1716-32 5. Bundred N. Breast pain. Clin Evid 2002 Jun;(7):1631-8 6. Danazol Product Information. Sanofi-Synthelabo Inc. February 2003. 7. Facts and Comparisons, St. Louis, efacts 2010 CliniSphere Version ISBN 1-57439-036-8 Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA DDAVP (desmopressin) Tablets: 0.1mg, 0.2mg; Nasal Spray/Rhinal Tube: 10mcg/spray (0.1mg/mL) FORMULARY STATUS: Formulary (generic) PA CRITERIA FOR APPROVAL: Tablets: Diagnosis of primary nocturnal enuresis in children 6 years of age and older. OR Diagnosis of central cranial (neurogenic) diabetes insipidus. NOTE: Tablet formulation will process at the point-of-sale for members 6 years old. Nasal Spray and Rhinal Tube: Diagnosis of central cranial (neurogenic) diabetes insipidus. If the above conditions are met, the request will be approved with a 12 month duration for generic medication; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: DAVP (desmopressin) Tablets: 0.1mg, 0.2mg Central Diabetes Insipidus: Antidiuretic hormone (ADH) replacement therapy in the management of central cranial (neurogenic) diabetes insipidus and for temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Ineffective for the treatment of nephrogenic diabetes insipidus. Primary Nocturnal Enuresis: May be used alone or adjunctive to behavioral conditioning or other nonpharmacological intervention. It is effective in some cases that are refractory to conventional therapies. DOSAGE AND ADMINISTRATION: Primary Nocturnal Enuresis: Individualize dosage of tablets according to response: DDAVP (desmopressin) Nasal Spray/Rhinal Tube: 10mcg/spray (0.1mg/mL) Central Diabetes Insipidus: Antidiuretic hormone (ADH) replacement therapy in the management of central cranial (neurogenic) diabetes insipidus and for temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Ineffective for the treatment of nephrogenic diabetes insipidus. Oral: Maximum Dosage: 0.6 mg at bedtime o Initial dose (> 6 years of age): 0.2mg at bedtime. The dose may be titrated up to 0.6mg to achieve the desired response. Fluid restriction should be observed and fluid intake should be limited to a minimum from 1 hour before desmopressin administration until the next morning or at least 8 hours after administration. Patients previously on intranasal DDAVP therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2mg at bedtime. Central cranial diabetes insipidus: Oral: Maximum Dosage: 1.2 mg/day o Adults and Children: Begin with 0.05 mg 2 times a day and adjust individually to their optimum therapeutic dose. Separately adjust each dose for an adequate diurnal rhythm of water turnover. Increase or decrease total daily dosage in the range of 0.1 to 1.2 mg, divided 2 or 3 times a day, as needed to obtain adequate antidiuresis. Fluid restriction should be observed. o Most patients in clinical trials found that the optimal dosage range is 0.1mg to 0.8mg daily, administered in divided doses. o The dosage must be determined for each individual patient and adjusted according to the diurnal pattern of response. o Begin therapy 12 hours after the last intranasal dose for patients previously on intranasal therapy.

o Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover. Intranasal: o Adults: 10mcg to 40mcg daily, either as a single dose or divided into 2 or 3 doses. Most adults require 20mcg daily in two divided doses. Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. o Children (3 months to 12 years of age): 0.05 to 0.3 ml daily, either as a single dose or in 2 divided doses. o Fluid restriction should be observed. o Administration: The nasal tube delivery system is supplied with a flexible calibrated plastic tube (rhinyle). Draw solution into the rhinyle. Insert one end of tube into nostril; blow on the other end to deposit solution deep into nasal cavity. The nasal spray pump also may be used Renal Insufficiency: DDAVP (oral and intranasal) is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min). REFERENCE: 1. Thiedke CC Nocturnal enuresis. Am Fam Physician 2003;67(7):1499-1510. 2. Neveus T Oxybutynin, Desmopressin, and enuresis. J Urol 2001;166(6):2459-2462. 3. Schulman SL, Stokes A, Salzman PM. The efficacy and safety of oral Desmopressin in children with primary nocturnal enuresis. J Urol 2001;166(6):2427-2431. 4. Evans JNC. Evidence based management of nocturnal enuresis. BMJ 2001;323(7322):1167-1169. 5. Shindel A; Tobin G; Klutke C. Hyponatremia associated with desmopressin for the treatment of nocturnal polyuria. Urology 2002 Aug;60(2):344. 6. Hvistendahl GM; Rawashdeh YF; Kamperis K; Hansen MN; Rittig S; Djurhuus JC. The relationship between desmopressin treatment and voiding pattern in children. BJU Int 2002 Jun;89(9):917-22. 7. Shord SS, et al. Coagulation products and their uses. Am J Health-Syst Pharm 2000; 57 (15): 1403-1417. 8. Facts and Comparisons, St. Louis, 2010 CliniSphere Version ISBN 1-57439-036-8; Record 13151. 9. Product Information. DDAVP Nasal Spray. Sanofi-Aventis U.S., LLC. July 2007. 10. Product Information. DDAVP Tablets. Sanofi-Aventis U.S., LLC. July 2007. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA DIAMOX SEQUEL (acetazolamide sustained release) Capsule: 500mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Diagnosis of chronic simple open angle glaucoma, or secondary glaucoma. and Documented trial and failure with therapeutic doses or intolerance to acetazolamide immediate release tablets. If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: For adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma; preoperatively in acute angle-closure glaucoma when delay of surgery is desired to lower intraocular pressure (IOP). Prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent. DOSAGE AND ADMINISTRATION: Glaucoma Adults & Pediatrics: 500 mg twice a day Acute Mountain Sickness Adults & Pediatrics: 500 to 1000 mg daily in divided doses REFERENCES: 1. Pikkel J; Beiran I; Ophir A; Miller B. Acetazolamide for central serous retinopathy. Ophthalmology 2002 Sep;109(9):1723-5. 2. Facts and Comparisons, St. Louis, 2010 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 3. Weinreb RN, Khaw PT. Primary open angle glaucoma. Lancet. 2004;363(9422):1711-1720. 4. Diamox Sequel Prescribing Information. Duramed Pharmaceuticals, Inc. July 2008. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA DOSTINEX (cabergoline) Tablet: 0.5mg FORMULARY STATUS: Formulary (generic) PA CRITERIA FOR APPROVAL: Diagnosis of hyperprolactinemia. Documented trial and failure with therapeutic doses or intolerance to bromocriptine therapy. If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: The treatment of hyperprolactinemic disorders, either idiopathic or because of pituitary adenomas. DOSAGE AND ADMINISTRATION: The recommended dosage of cabergoline for initiation of therapy is 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice weekly to < 1 mg twice a week according to the patient's serum prolactin level. Dosage increases should not occur more rapidly than every 4 weeks. If the patient does not respond adequately and no additional benefit is observed with higher doses, use the lowest dose that achieved maximal response and consider other therapeutic approaches. After a normal serum prolactin level has been maintained for 6 months, cabergoline may be discontinued. Periodically monitor the serum prolactin level to determine if or when treatment with cabergoline should be reinstituted. The durability of efficacy beyond 24 months of therapy with cabergoline has not been established. REFERENCES: 1. Colao A, Vitali G, Cappabiana P, Briganti F, et al. Outcome of carb of carbergoline treatment in men with prolactinoma: effects of a 24 month treatment on prolactin levels, tumor mass, recovery or pituitary function, and semen analysis. J Clin Endocrinol Metab 2004;89(4):1704-1711. 2. Schlechte JA. Prolactinoma. NEJM 2003;349(21):2035-2041. 3. Serri O, Chik CL, Ur E, Ezzat S. Diagnosis and management of hyperprolactinemia. Can Med Assoc J 2003;169(6):575-581. 4. Keogh MA, Wittert GA. Effect of cabergoline on thyroid function in hyperprolactinemia. Clin Endocrinol (Oxf) 2002 Nov;57(5):699. 5. Lohmann T, Trantakis C, Biesold M, Prothmann S, Guenzel S, Schober R, Paschke R. Minor tumor shrinkage in nonfunctioning pituitary adenomas by long-term treatment with the dopamine agonist cabergoline. Pituitary 2001 Aug;4(3):173-8. 6. Liu GT. Pituitary Adenomas. Curr Treat Options Neurol 2002 Jul;4(4):261-269. 7. Facts and Comparisons, St. Louis, efacts 2009 2010 CliniSphere Version ISBN 1-57439- 036-8. 8. Dostinex Prescribing Information. Pharmacia & Upjohn Company. January 2008. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA EFFIENT (prasugrel) Tablet: 5, 10 mg FORMULARY STATUS: Non-formulary PA CRITERIA FOR APPROVAL: 1. Diagnosis of unstable angina or non-st-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI) 2. History of primary or delayed percutaneous coronary intervention (PCI). 3. No active pathological bleeding. 4. No history of transient ischemic attacks or stroke. If the above conditions are met, the request will be approved with a12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: To reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: Patients with unstable angina (UA) or non-st-elevation myocardial infarction (NSTEMI). Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. DOSAGE AND ADMINISTRATION: Initiate Effient treatment as a single 60 mg oral loading dose and then continue at 10 mg orally once daily. Patients taking Effient should also take aspirin (75 mg to 325 mg) daily. Effient may be administered with or without food. Use of prasugrel is generally not recommended in patients 75 years of age and older except in high-risk situations (diabetes and history of MI) in which its effect appears to be greater and its use may be considered. Dosing in Low Weight Patients: Compared to patients weighing 60 kg, patients weighing < 60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients < 60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied. REFERENCES: 1. Effient. Prescribing Information. Eli Lilly and Co. December 2010. 2. Wiviott S, Antman E, Gibson C, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J. 2006 Oct;152(4):627-35. 3. Jakubowski J, Matsushima N, Asai F, et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in health humans. Br J Clin Pharmacol. 2007 Apr;63(4):421-430. 4. Wiviott S, Braunwald E, Angiolillo D, et al.. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in Myocardial Infarction 38. Circulation. 2008 Oct;118(16):1626-1636. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SOUTH REGION PRIOR AUTHORIZATION CRITERIA ELIDEL (pimecrolimus) Cream: 1% STATUS Requires PA PA CRITERIA FOR APPROVAL INITIAL PA: Diagnosis of mild to moderate atopic dermatitis. AND Non-immunocompromised patient. AND Patient 2 years of age or older. AND Patient has not adequately responded to two different preferred prescription strength corticosteroid therapies in the last 8 weeks. OR Physician provides valid rationale why corticosteroid therapy is inappropriate (ex., use on the face). If the above conditions are met, the request will be approved with a 3 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. RENEWAL PA: Diagnosis of mild to moderate atopic dermatitis. Non-immunocompromised patient. Patient 2 years of age or older. Documentation that patient has been re-examined by their health care provider and continuation of Elidel therapy is appropriate. If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred for medical necessity review. FDA INDICATIONS Mild to Moderate Atopic Dermatitis: Elidel Cream 1% is indicated as second-line therapy for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. DOSAGE AND ADMINISTRATION Apply a thin layer to the affected skin areas twice daily. ***Elidel should not be used with occlusive dressings. ***Stop using when signs and symptoms of atopic dermatitis resolve. ***If signs and symptoms persist beyond 6 weeks, patients should be re-examined by their health care provider to confirm diagnosis of atopic dermatitis. ***Continuous long-term use of topical calcineurin inhibitors, including Elidel should be avoided, and application should be limited to areas of involvement with atopic dermatitis. REFERENCES 1. Elidel. Prescribing Information. Valeant Pharmaceuticals North America LLC. July 2013. 2. Hanifin JM, Cooper KD, Ho VC, Kang S, et al. Guidelines of Care for Atopic Dermatitis. J Am Acad Dermatol 2004;50(3):485-6. 3. Topical pimecrolimus for treatment of atopic dermatitis. Med Lett Drugs Ther, May 27 2002;44(1131): 48-50. 4. Kapp A, Papp K, Bingham A, et al. Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug. J Allergy Clin Immunol (United States), Aug 2002; 110(2):277-84. 5. Meurer M, Folster-Holst R, Wozel G, et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Dermatology,2002;205(3):271-7. Revision/Review Date: July 2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ELMIRON (pentosan polysulfate sodium) Capsule: 100mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of interstitial cystitis. If the above conditions are met, the request will be approved for duration of 6 months; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: The relief of bladder pain or discomfort associated with interstitial cystitis. DOSAGE AND ADMINISTRATION: The recommended dose of Elmiron is 300 mg/day taken as one 100 mg capsule orally 3 times daily. Take with water > 1 hour before or 2 hours after meals. REFERENCES: 1. Dell JR, Parsons CJ. Multimodal therapy for interstitial cystitis. J Reprod Med 2004;49(3S):243-252. 2. Moldwin RM, Sant GR. Interstitial cystitis: a pathophysiology and treatment update. Clin Obstet Gynecol 2002 Mar;45(1):259-72. 3. Metts JF. Interstitial cystitis: urgency and frequency syndrome. Am Fam Physician 2001 Oct 1;64(7):1199-206. 4. Facts and Comparisons, St. Louis, efacts 2010 CliniSphere Version ISBN 1-57439-036-8. 5. ELMIRON Prescribing Information. Ortho-McNeil Pharmaceutical, INC. December 2008. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ENTOCORT EC (budesonide) Capsule: 3mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of mild to moderate active or remissive Crohn s disease involving the ileum and/or the ascending colon. AND Prescription written by a gastroenterologist. AND Documented trial and failure with 16 weeks of therapy at therapeutic doses of at least two first-line therapies of sulfasalazine, mesalamine and prednisone. If the above conditions are met, the request will be approved with up to 16 weeks duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Treatment of mild-to-moderately active Crohn's disease involving the ileum and/or the ascending colon. Treatment for maintenance of clinical remission of mild to moderate Crohn s disease involving the ileum and/or the ascending colon for up to 3 months. DOSAGE AND ADMINISTRATION: Active Crohn s Disease: o Adults: Take 9 mg once daily in the morning for up to 8 weeks. Swallow capsules whole; do not chew or break. Safety and efficacy of budesonide in the treatment of active Crohn's disease have not been established beyond 8 weeks. For recurring episodes of active Crohn's disease, a repeat 8-week course of budesonide can be given. Remissive Crohn s Disease: o Adults: Budesonide capsules 6mg is recommended once daily for maintenance of clinical remission up to 3 months. If symptom control is still maintained at 3 months an attempt to taper to complete cessation is recommended. Continued treatment with budesonide capsules 6 mg for more than 3 months has not been shown to provide substantial clinical benefit. Changing chronic oral steroid therapy: o If switching between chronic oral steroid treatment and budesonide capsules, tapering of the previous should begin immediately. REFERENCES: 1. Knutson D, Greenberg G, Cronau H. Management of crohns s disease. Am Fam Physician 2003;68(4):707-718 2. Sandborn WJ. Evidence based treatment algorithm for mild to moderate crohn s disease. Am J Gastroenterol 2003;98(12S);S1-S5. 3. Malchow H, Ewe K, Brandes JW, et al. European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984;86:249-266. 4. Hoefer KN. Oral Budesonide in the management of crohn s disease. Ann Pharmacotherapy. 2003;37(10):1457-1464 5. Summers RW, Switz DM, Sessions JT Jr, et al. National Cooperative Crohn's Disease Study: results of drug treatment. Gastroenterology. 1979;77:847-869. 6. Hanauer SB, et al. Management of Chron s diease in adults. Am J Gastroenterol 2001. Mar 96: 635-43. 7. Ferguson A, Campieri M, Doe W, Persson T, Nygard G. Oral budesonide as maintenance therapy in Crohn's disease--results of a 12-month study. Global Budesonide Study Group. Aliment Pharmacol Ther. 1998;12:175-183. 8. Campieri M, Ferguson A, Doe W, Persson T, Nilsson LG. Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group. Gut. 1997;41:209-214. 9. Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6-mercaptopurine in Crohn's disease: a meta-analysis. Ann Intern Med. 1995;123:132-142. 10. Korelitz B, Hanauer SB, Rutgeerts P, Present D, Peppercorn M. Post-operative prophylaxis with 6-MP, 5-ASA or placebo in Crohn's disease: a 2 year multicenter trial. Gastroenterology. 1998;114:A1011.

11. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6- mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol. 1996;91:423-433. 12. Facts and Comparisons, St. Louis, efacts 2010 CliniSphere Version ISBN 1-57439-036-8. 13. Entocort EC Prescribing Information. AstraZeneca AB. June 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION CRITERIA EPOGEN (epoetin alfa): 2,000 units/ml, 4,000 units/ml, 10,000 units/ml, 3,000 units/ml, 20,000 units/ml, 40,000 units/ml OMONTYS (peginesatide): single-use vials: 2mg, 3mg, 4mg, 5mg, 6mg single use pre-filled syringes: 1mg, 2mg, 3mg, 4mg, 5mg, 6mg multiple use vials: 10mg/ml and 20mg/2ml PA Criteria for Approval of Administration of Epogen in ESRD Patients Treated at Dialysis Centers). ESRD: End Stage Renal Disease Patient is being treated at a dialysis center. AND The necessary lab work (listed below) is documented on the PA form or submitted with request; -Hemoglobin last 3 months results (to determine rolling Hgb) -Hematocrit last 3 months results (to determine rolling Hct) -Reticulocytes within past 2 months. -Serum ferritin within past 2 months -Transferrin saturation within past 2 months -Serum iron within past 2 months. -Total Iron Binding Capacity (TIBC) within past 2 months -Red cell indices (MCV, MCHC, RDW etc.) within past month -Vitamin B12 and Folate levels within past 2 months -History of Epogen usage If all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the patient into one of the following categories based on diagnosis: Place the patient into one of the following categories -Epogen treatment naïve with normal iron status (Section A) -Epogen treatment naïve with iron deficiency (Section B) -Receiving Epogen treatment with normal iron status (Section C) -Receiving Epogen treatment with iron deficiency (Section D) Section A: Epogen treatment naïve with normal iron status (TSAT > 20% and Ferritin > 100ng/ml) The patient has a hemoglobin < 10g/dL and / or hematocrit <33%. Epogen dosing is being initiated at 100 units/kg- 3 times a week (TIW) or less. The patient is receiving maintenance iron therapy (25-125 mg IV once weekly or >200 mg elemental iron orally daily). If all of the above conditions are met, the request will be approved with a 3-month duration, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section B: Epogen treatment naïve with iron deficiency (TSAT < 20% and Ferritin < 100ng/ml) The patient has a hemoglobin <10.0g/dL and/or hematocrit <33%. The patient is in the process of receiving parental iron supplementation (100 mg IV every hemodialysis for 10 doses or 125 mg IV for 8 doses, maybe repeated if TSAT is less 20% and/or serum ferritin is less than 100 ng/ml, when TSAT >20% and Ferritin > 100 ng/ml then 50-100mg IV every week for 10 doses is recommended). The patient s Epogen dose is less than or equal to 100 units/kg- 3 times a week (TIW). If all of the above conditions are met, the request will be approved with a 2-month duration to allow follow up on outcome of iron supplementation; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section C: Existing therapy with Epogen with normal iron status (TSAT > 20% and Ferritin > 100ng/ml) The patient has a hemoglobin < 11.5 g/dl and/or hematocrit <36%

The patient s hematocrit increased greater than 8 percentage points in the past month, or Hgb increased by more than 1g/dl in a two week period, after starting current dose and the Epogen dose has been reduced by at least 25% compared to the last course of therapy and therapy withheld for 1-2 weeks. If the patient s Hgb/Hct is below target range after receiving therapy for at least 4 weeks and the dose is the same as last month or was increased by no more than 25% of the previous dose. If the patient s current Epogen dose was started less than 8 week ago and their hematocrit has increased by less than 4 percentage points over the past 2 weeks or less than 8 percentage points over the last 4 weeks and the ordered dose of Epogen is the same as last month or less. If the patient s Hgb/Hct is in target range (Hct. 33-36 and Hgb. 11-12) and the ordered dose is either reduced or the same dose as the previous month. The ordered dose is not an increase in dosage that is within 4 weeks of last dosage change or start of therapy with a medical reason being provided for an early increase. If the patient s hematocrit exceeds 36% or Hgb exceeds < 11.5 g/dl despite dose reduction, the Epogen dose was withheld until hematocrit dropped to 36% or less and the ordered Epogen dose was reduced by 25%. The patient is receiving maintenance iron therapy (25-125 mg IV once weekly or >200 mg elemental iron orally daily). If the dose is greater than 300 units/kg TIW, then documentation (within the past 2 months) was provided that maximum iron supplementation was attempted (despite TSAT > 20% and ferritin >100 ng/ml, the patient received 2 courses of iron supplementation at 50-100 mg per week x 10 doses to observe H/H response. After 2 nd course, if no increase in H/H, but TSAT or ferritin increases, then weekly iron dose should be reduced to maintain TSAT > 20% and serum ferritin >100 ng/ml. If H/H did increase after 2 nd course of iron, or remained stable after reduced Epogen dose, then a 3rd course of iron 100 mg/week x 10 dose is reasonable to achieve and maintain target H/H). Along with documentation of iron dosing, documentation (within the past 2 months) was submitted from a hematologist recommending the current dose if all reversible causes for Epogen resistance have been ruled out. If all of the above conditions are met, the request will be approved with a 3-month duration, if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Section D: Existing therapy on Epogen with iron deficiency (TSAT < 20% and Ferritin < 100ng/ml) The patient has a hemoglobin <11.5 g/dl and/or hematocrit <36% The patient is currently in the process of receiving iron supplementation (Ex:100 mg IV every hemodialysis for 10 doses, which may be repeated if TSAT is less 20% and/or serum ferritin is less than 100 ng/ml, when TSAT >20% and ferritin > 100 ng/ml then 50-100mg IV every week for 10 doses is recommended followed by maintenance dosing 25-125 mg/week) The ordered dose is an increase in dosage that is within one-month time of last dosage change or start of therapy, and a medical reason was provided for an early increase. The Epogen dose is less than or equal to 100 units/kg TIW. If all of the above conditions are met, the request will be approved with a 2-month duration to allow follow up on outcome of iron supplementation; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Epogen: Treatment of anemia of chronic renal failure patients Treatment of anemia in Zidovudine-treated HIV-infected patients Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown reduction in the need for RBC transfusion I patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. o Epogen is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy. o Epogen is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of Epogen on progression-free and overall survival. o Epogen is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate o deficiencies, hemolysis, or gastrointestinal bleeding. Procrit use has been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being Treatment of anemic patients (Hgb>10 to <13 g/dl) who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery to reduce the need for allogenic blood transfusion

Omontys: Treatment of anemia of chronic kidney disease (CKD) in adult patients on dialysis Omontys is not indicated and is not recommended for use: o In patients with CKD not on dialysis o In patients receiving treatment for cancer and whose anemia is not due to CKD o As a substitute for RBC transfusions in patients who require immediate correction of anemia o Omontys has not been shown to improve symptoms, physical functioning or health-related quality of life DOSAGE AND ADMINISTRATION: CKD patients: General Therapeutic Guidelines in CKD Patients for Epoetin Alfa Starting dose (initiate Epogen treatment when the hemoglobin level is less than 10 g/dl) Adults: 50 to 100 Units/kg TIW Pediatric: 50 Units/kg TIW Maximum dose (with normal Iron stores) Intravenous administration 300 units/kg TIW **Doses greater than maximum doses require hematologist consultation and recommendation. Reduce dose by 25% or more when max dose for the treatment of anemia caused by zidovudine in HIV-infected patients. There are no wellestablished maximum doses for the other approved indications. 1) Hgb increases by more than 1 g/dl in 2-week period Dose should be temporarily withheld when Hgb approaches or exceeds 11g/dL, reduce or interrupt the dose of Epogen. Therapy should be reinitiated at a dose approximately 25% below the previous dose. Increase dose up to 25% of previous dose if: 1) Hgb is < 10 g/dl. AND 2) Hbg has not increased by more than 1 g/dl after 4 weeks of therapy Discontinue therapy when Maintenance dose Suggested target hematocrit and hemoglobin The patient did not respond adequately over a 12-week escalation period. Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. 33% to 36% or 11 to 12 gm/dl Dose adjustment should not be made more frequently than once a month, unless clinically indicated. After any dose adjustment, determine the hematocrit twice weekly for at least 2 to 6 weeks. If the hematocrit is increasing and approaching 36%, reduce the dose to maintain the suggested target hematocrit range. If the reduced dose does not stop the rise in hematocrit and it exceeds 36%, temporarily withhold doses until the hematocrit begins to decrease, then reinitiate at a lower dose. At any time, if the hematocrit increases by > 4 points in a 2-week period, immediately decrease the dose. After the dose reduction, monitor the hematocrit twice weekly for 2 to 6 weeks and make further dose adjustments as outlined in the maintenance dose section. If a hematocrit increase of 5 to 6 points is not achieved after an 8-week period and iron stores are adequate (see Delayed or diminished response), the dose may be incrementally increased. Further increases may be made at 4- to 6-week intervals until the desired response is attained. Omontys: Initiate Omontys treatment when the hemoglobin level is less than 10 g/dl The recommended starting dose for the treatment of anemia in patients who are not currently treated with an ESA is 0.04 mg/kg body weight administered as a single intravenous or subcutaneous injection once monthly.

Estimated Omontys Starting Doses for Patients Based on Previous Weekly ESA Dose Previous Total Weekly Epoetin Alfa Dose (U/week) Previous Weekly Darbepoetin Alfa Dose (mcg/week) OMONTYS Dose Once Monthly (mg/month) Less than 2,500 Less than 12 2 2,500 to less than 4,300 12 to less than 18 3 4,300 to less than 6,500 18 to less than 25 4 6,500 to less than 8,900 25 to less than 35 5 8,900 to less than 13,000 35 to less than 45 6 13,000 to less than 19,000 45 to less than 60 8 19,000 to less than 33,000 60 to less than 95 10 33,000 to less than 68,000 95 to less than 175 15 greater than or equal to 68,000 greater than or equal to 175 20 REFERENCES: 1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, September 2007. Am J Kidney Dis Vol 50 (3): pgs. 462-530. 2. National Kidney Foundation. KDIGO Clinical Practice Guidelines for Anemia in Chronic Kidney Disease. August 2012. Vol 2(4): pgs. 279-335. 3. Coyne DW, Kapoain T, Suki W, et al. Ferric Gluconate is Highly Efficacious in Anemic Hemodialysis Patients with High Serum Ferritin and Low Transferrin Saturaion: Results of the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) Study. American Society of Nephrology 2007: 18; 975-84. 4. Amgen Inc. Epogen (Epoetin Alfa). Prescribing Information, May/2012. 5. Takeda Pharmaceuticals. Omontys (peginesatide ). Prescribing Information, 12/2012. Revision/Review Date: 06/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Erbitux (cetuximab): 100 mg/ 50 ml sterile, preservative-free injectable liquid single-use vial, 200mg/100 ml, preservative-free injectable liquid single-use vial FORMULARY STATUS: Non Formulary Section I. PRIOR AUTHORIZATION CRITERIA FOR INITIAL APPROVAL PA Criteria for Initial Approval 1. Documentation submitted indicates an oncologist prescribed the Erbitux at an FDA approved or at a dose that is supported by the medical compendium as defined by the Social Security Act or per the NCCN or ASCO standard of care guidelines. If the above conditions are met, the request will be referred to a Medical Director. If all of the above conditions are met, place the member into one of the following categories based on diagnosis and review for medical necessity: -Treatment of Colorectal Cancer: go to Section II. -Treatment of Head and Neck Cancer: go to Section III. Section II. Colorectal Cancer 1. The member has documented colorectal cancer and the tumor does not have the KRAS mutations in codon 12 or 13 (KRAS wild-type gene meaning no mutation in codon 12 or 13). 2. When ordered as monotherapy, submitted documentation indicates that patient is intolerant or refractory to irinotecanand oxaliplatin-based chemotherapy regimens. 3. When ordered in combination with irinotecan, submit documentation indicating patient refractory to irinotecan-based chemotherapy If the above conditions are met, the request will be approved for up to 12-weeks of therapy, if all of the above are not met, the request will be referred to a Medical Director. Section III. Head and Neck Cancer 1. The member has documented Squamous Cell Carcinoma of the Head and Neck (SCCHN). 2. If the member has locally or regionally advanced squamous cell carcinoma of the head and neck, documentation was submitted indicating concurrent radiation therapy was ordered with Erbitux. 3. If Erbitux is being used as a single agent then: then member must have recurrent or metastatic squamous cell carcinoma of the head and neck and documentation must be submitted (consistent with pharmacy claims data) indicating treatment failure on prior platinum-based therapy (i.e. cisplatin or carboplatin) If the above conditions are met, the request will be approved for up to 12-weeks of therapy, if all of the above are not met, the request will be referred to a Medical Director. REAUTHORIZATION CRITERIA: 1. The member has been receiving therapy and had a documented positive response (e.g., complete response, partial response or stable disease or improved ECOG performance status score) or tolerating Erbitux treatment. 2. Documentation submitted indicates an oncologist prescribed the Erbitux at an FDA approved or medically accepted dosage. If all the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria were not met, the request will be referred to a Medical Director for medical necessity review. FDA APPROVED INDICATIONS: Squamous Cell Carcinoma of the Head and Neck (SCCHN): Erbitux, in combination with radiation therapy, is indicated for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. Erbitux, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed. Colorectal Cancer: Erbitux, used in combination with irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory or intolerant to irontecan-based chemotherapy.

Erbitux, administered as a single agent, is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who failed both irinotecan- and oxaliplatin-based regimens or in patients who are intolerant to irinotecanbased regimens. Erbitux, administered as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant to irinotecan-based regimens. Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for Erbitux in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Erbitux is not recommended for the treatment of colorectal cancer with these mutations. DOSAGE AND ADMINISTRATION: Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy Erbitux in combination with radiation therapy: Erbitux, 400 mg/m 2 as an initial loading dose (first infusion) administered as a 120 minute IV infusion given one week prior to initiation of a course of radiation therapy (maximum infusion rate 10 mg/min). The recommended weekly maintenance dose (all other infusions) is 250 mg/m 2 infused over 60 minutes (maximum infusion rate 10 mg/min) weekly for the duration of radiation therapy (typically 6-7 weeks). Administer 1 hour prior to radiation if possible. Recurrent or metastatic squamous cell carcinoma of the head and neck as monotherapy for patients whom prior platinumbased therapy has failed Erbitux, 400 mg/m 2 as an initial loading dose (first infusion) administered as a 120 minute IV infusion (maximum infusion rate is 10 mg/minute followed by 250 mg/m 2 infused over 60 minutes given weekly until disease progression or unacceptable toxicity. EGFR-expressing, metastatic colorectal carcinoma in combination with irinotecan, in patients refractory to irinotecan-based chemotherapy and as a single agent in patients intolerant to both irinotecan- and oxaliplatin-based regimens Erbitux, 400 mg/m 2 as an initial loading dose (first infusion) administered as a 120 minute IV infusion (maximum infusion rate 10 mg/min) followed by 250 mg/m 2 (all other infusions) infused over 60 minutes given as a weekly maintenance dose until disease progression or unacceptable toxicity. DOSE MODIFICATIONS: Infusion Reactions If the patient experiences a NCI CTC Grade 1 or 2 or non-serious Grade 3 or 4 infusion reaction, the infusion rate should be permanently reduced by 50 %. Erbitux should be immediately and permanently discontinued in patients who experience serious and severe (NCI CTC Grade 3 or 4) infusion reactions. Dermatologic Toxicity and Related Disorders Dosage modifications for dermatologic toxicity are recommended for severe acneform rash (NCI CTC Grades 3 or 4) as specified in Table 1 below. No dosage modifications are recommended for severe radiation dermatitis. Table 1. Erbitux Dose Modification Guidelines Severe Acneform Rash Erbitux Outcome Erbitux Dose Modification 1 st Occurrence Delay infusion 1 to 2 weeks Improvement Continue at 250 mg/m 2 No Improvement Discontinue Erbitux 2 nd Occurrence Delay infusion 1 to 2 weeks Improvement Reduce dose to 200 mg/m 2 No Improvement Discontinue Erbitux 3 rd Occurrence Delay infusion 1 to 2 weeks Improvement Reduce dose to 150 mg./m 2 No Improvement Discontinue Erbitux 4 th Occurrence Discontinue Erbitux GLOSSARY: Erbitux has been associated with severe hypomagnesemia (NCI CTC Grade 3 and 4) as well as hypokalemia and hypocalcemia. Periodic monitoring for these electrolyte deficiencies during treatment on Erbitux and for 8 weeks following the completion of therapy is recommended by the product labeling and compendia. Normal Adult Chemistry Values (may vary

slightly based on lab) Calcium: 8.6-10.3 mg/dl Magnesium: 1.6-2.5 mg/dl Potassium: 3.5-5.2 meq/l Erbitux has been associated with severe (NCI-CTC Grade 3 and 4) anemia and leukopenia when used in combination with irinotecan for colorectal cancer and additionally thrombocytopenia in head and neck cancer patients. Normal Adult Complete Blood Count with Differential Values (may vary slightly based on lab) Hemoglobin (Hb) g/dl 12.0-15.0 Hematocrit (Hct) % 36-44 Platelets (x10 3 /mm 3 ) 150-450 White blood cells (WBC) x10 3 /mm 3 4.5-11.0 Segs 35-66 Bands 5-11 Lymphs 24-44 Monos 3-6 Eosinophils 0-3 Basophils 0-1 ANC=WBC x (Segs + Bands) Eastern Cooperative Oncology Group (ECOG) Performance Status: is used by doctors and researchers to assess disease progression, how the disease affects daily living abilities and determine appropriate treatment and prognosis. Grade ECOG ECOG PERFORMANCE STATUS* 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 5 Dead * As published in Am. J. Clin. Oncol.:Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chair. REFERENCES: 1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Colon Cancer. Version 2.2009. 2. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2009. 3. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Rectal Cancer. Version 2.2009. 4. Baselga J. Trigo J. Bourhis J. et al. Phase II multicenter study of antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck. Journal of Clinical Oncology. 2005;23(24):5568-5577. DOI: 10.1200/JCO.2005.07.119. 5. Am. J. Clin. Oncol.:Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. Available at http://www.ecog.org/general/perf_stat.html. Accessed 02/25/08. 6. Bristol-Myers Squibb Company. Erbutix (cetuximab) package insert. Princeton, NJ; Sept 2010. 7. Erbitux Prescribing Information. Bristol-Myers Squibb Lilly. September 2010 Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA EXJADE (Deferasirox) Tablet for Oral Suspension: 125mg, 250mg, & 500mg FORMULARY STATUS: Non-formulary PA CRITERIA FOR APPROVAL: For Pediatric Population Patient must be > 2 years old and < 21 years old and Diagnosis of chronic iron overload due to blood transfusions and Patient receiving blood transfusions on a regular basis/participating in blood transfusion program and Serum Ferritin concentration is consistently > 1000 mcg/l. If the serum ferritin levels fall consistently below 500 mcg/l, Exjade must be discontinued and Initial starting dose 20mg/kg/day. Maximum maintenance dose of 40mg/kg/day. and Approval for a 3-month period. After 3 months patient must be re-evaluated based on above criteria. For Adult Population Patient must be > 21 years old and Diagnosis of chronic iron overload due to blood transfusions and Patient receiving blood transfusions on a regular basis/participating in blood transfusion program and Serum Ferritin concentration is consistently > 1000 mcg/l. If the serum ferritin levels fall consistently below 500 mcg/l, Exjade must be discontinued and Documented patient is unable to use Deferoxamine (Desferal) parenterally and Initial starting dose 20mg/kg/day. Maximum maintenance dose of 40mg/kg/day, and Approval for a 3-month period. After 3 months patient must be re-evaluated based on above criteria. If the above conditions are met, the request will be approved within appropriate dosing with a 3- month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATION: For the treatment of chronic iron overload due to blood transfusions in patients two years of age or older. DOSAGE AND ADMINISTRATION: The recommended initial starting dose of Exjade is 20mg/kg/day, taken on an empty stomach at least 30 minutes before food. Doses should be rounded to the nearest available tablet strength. Dose adjustments should be made in increments of 5 to 10mg/kg/day. In patients not adequately controlled with doses of 30mg/kg/day (e.g. serum ferritin levels persistently above 2,500mcg/L and not showing a decreasing trend over time), doses of up to 40mg/kg/day may be considered. Doses above 40 mg/kg are not recommended. Tablets must be dispersed in water, orange juice, or apple juice to form a suspension. RENAL DOSE ADJUSTMENTS Pediatrics: The dose should be reduced by 10mg/kg, if serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits. Adults: The daily dose should be reduced by 10mg/kg if a rise in serum creatinine to > 33% above the average of the pretreatment measurement is seen at two consecutive visits, and cannot be attributed to other causes.

HEPATIC DOSE ADJUSTMENTS Dose modifications or interruptions should be considered for severe or persistent elevations. WARNING Auditory disturbances and ocular disturbances have been reported at a frequency of <1% with Exjade therapy in the clinical studies. Auditory and ophthalmic testings are recommended before starting Exjade treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, dose reduction or interruption should be considered. REFERENCE: 1. Exjade Product Information. Novartis Pharmaceuticals Corporation. January 2010. 2. Data on File. Novartis Pharmaceuticals Corporation. February 2006. 3. Drugs Facts and Comparisons 4.0. 2010. Deferasirox available from http://online.factsandcomparisons.com/printmonodisp.aspx?id=239589. Accessed August 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FARESTON (toremifene) Tablet: 60mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Postmenopausal woman with the diagnosis of metastatic breast cancer. AND Documented intolerance to tamoxifen. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor (ER)positive or ERunknown tumors. DOSAGE AND ADMINISTRATION: Dosage is 60 mg once daily, generally continued until disease progression is observed. REFERENCES: 1. Haskell SG. Selective estrogen receptor modulators. South Med J 2003;96(5);469-476. 2. Riggs BL, Hartmann LC. Selective estrogen receptor modulators-mechanism of action and application to clinical practice. NEJM 2003;348(7):618-629. 3. Parker LM. Sequencing of hormonal therapy in postmenopausal women with metastatic breast cancer. Clin Ther 2002;24 Suppl C:C43-57. 4. Johnston SR. Endocrine manipulation in advanced breast cancer: recent advances with SERM therapies. Clin Cancer Res 2001 Dec;7(12 Suppl):4376s-4387s; discussion 4411s-4412s. 5. Product Information. Fareston (toremifene). GTx, Inc. March 2011. 6. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version V.2.2011. Available at www.nccn.org. 7. Pagani, O., et al. Tremifene and Tamoxifen are Equally Effective for Early-Stage Breast Cancer: First Results of International Breast Cancer Study Group Trials 12-93 and 14-93. Annuals of Oncology. 2004. 15: 1749-1759. 8. Milla-Santos, A., et al. Phase III Randomized Trial of Toremifene vs. Tomoxifen in Hormonodependant Advanced Breast Cancer. Breast Cancer Research and Treatment. January 2001. 65: 119-124. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FLOVENT (fluticasone) HFA Inhaler: 44mcg, 110mcg, 220mcg FORMULARY STATUS: Formulary NOTE: Flovent HFA Inhaler 44mcg and Flovent HFA 110mcg strength inhalers will process at the point of sale without prior authorization required when prescribed in the appropriate dosage quantities for patients 4 years and older. PA CRITERIA FOR APPROVAL FOR FLOVENT HFA 220mcg: Diagnosis of asthma. AND Documented therapy with Flovent HFA 110mcg within the previous 30 days. If the above conditions are met, the request will be approved with a up to a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: For the maintenance treatment of asthma as prophylactic therapy in patients 4 years of age and older. It is also indicated for patients requiring oral corticosteroid therapy for asthma. Many of these patients may be able to reduce or eliminate their requirement for oral corticosteroids over time. Fluticasone is not indicated for relief of acute bronchospasm. DOSAGE AND ADMINISTRATION: Individual patients will experience a variable time to onset and degree of symptom relief. Improvement can occur within 24 hours of beginning treatment, although maximum benefit may not be achieved for 1 to 2 weeks or longer. After asthma stability has been achieved, titrate to the lowest effective dose to reduce side effect possibility. For patients not responding adequately to the starting dose after 2 weeks, higher doses may provide additional asthma control based on the table below: Recommended Doses for Fluticasone Aerosol Previous Recommended Highest therapy starting dose recommended dose Age > 12 years Bronchodilators alone 88 mcg twice daily 440 mcg twice daily Inhaled corticosteroids 88-220 mcg twice daily 440 mcg twice daily Oral corticosteroids* 440 mcg twice daily 880 mcg twice daily Age 4-11 years** 88mcg twice daily 88mcg twice daily * Concomitant systemic corticosteroid therapy: For patients currently receiving chronic oral corticosteroids, reduce prednisone no faster than 2.5 to 5mg/day on a weekly basis, beginning after at least 1 week of aerosol therapy. Monitor patients for signs of asthma instability, including serial objective measures of airflow, and for signs of adrenal insufficiency. Decrease fluticasone dosage to the lowest effective dose once prednisone reduction is complete. **Recommended pediatric dosage is 88mcg twice daily regardless of prior therapy. Advise patients to rinse mouth after inhalation. Currently receiving inhaled corticosteroid therapy: Starting doses above 88 mcg twice daily may be considered for patients with poorer asthma control or those who gave previously required doses of inhaled corticosteroid that are in the higher range for that specific agent. References:

1. National Asthma Education and Prevention Program Clinical Practice Guidelines: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma: National Institutes of Health. National Heart, Lung and Blood Institute. NIH Publication No. 97-4051 August 28, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm; http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf 2. Facts and Comparisons, St. Louis, efacts 2010 CliniSphere Version ISBN 1-57439-036-8 3. Flovent HFA Product Information. GlaxoSmithKline. July 2008. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FUZEON (Enfuvirtide): 90mg vial FOR ADULTS: PA CRITERIA FOR INITIAL APPROVAL: The patient has documented treatment failure to at least one sensitivity-assisted antiretroviral therapy regimen and at least two drug regimens that included two different NRTIs and two or more PIs (see table 1), or the patient has a documented medical reason for not trying two drug regimens that included two different NRTIs and two or more PIs. Refer to Fuzeon Medication History Form and any other documentation sent by prescriber. Failure may be defined as: 1. Less than a one-log drop in viral load after 12 weeks therapy on a regimen 2. Repeated viral detection in plasma after initial suppression 3. A viral load of > 400 copies/ml after 24 weeks of continued treatment OR > 50 copies/ml after 48 weeks of continued treatment. 4. A decrease in CD 4 count to less than baseline. 5. A failure to increase CD4 count by 25 50 cells/mm 3 above the baseline count over the first year of therapy. 6. Clinical deterioration: defined as new AIDS-defining illness concurrent with a virological response (greater than a one-log drop) on current regimen Recent (within 30 days or while patient was on current medication regimen) genotype and phenotype testing result was submitted with request for Fuzeon to determine optimal regimen of at least two sensitive and tolerated anti-retroviral medications and to eliminate previously ineffective anti-retroviral medications, or there are less than two effective medications based on sensitivity testing and the patient is at risk for opportunistic infection or death. The patient has a documented adherence level on taking anti-retroviral therapy of greater than 80% and any issue that may have caused a decrease in adherence in the past (drug or alcohol abuse, difficulty of dosing schedule, etc.) has been addressed. Documentation of pretreatment CD 4 count and viral RNA was submitted with request. If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-APPROVAL: Documentation of current background drug therapy was submitted with request (Fuzeon is not recommended as monotherapy or to be used without optimal oral therapy). For the initial reauthorization: documentation submitted of a viral load drop of at least a one-log decrease from baseline after 12 weeks of starting therapy for requests to continue therapy beyond 16 weeks, or there is documentation provided that the patient has documented clinical improvement (i.e. increased CD 4 count) with treatment. After the initial reauthorization: documentation submitted of current (within the past 30 days) CD 4 count and HIV RNA viral load. If the patient has been on Fuzeon therapy AND there is an increase of at least 2 log in viral load or a 30% decline in CD4 counts from baseline then current phenotype/genotype testing (within the past 30 days) must be submitted to indicate continued susceptibility of the HIV virus to Fuzeon. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FOR CHILDREN: PA CRITERIA FOR INITIAL APPROVAL: Documentation that the patient is pre-pubertal. The patient has documented treatment failure to at least two drug regimens that included two different NRTIs and two or more PIs (see table 1), or the patient has a documented medical reason for not trying two drug regimens that included two different NRTIs and two or more PIs. Refer to Fuzeon Medication History Form and any other documentation sent by prescriber. Failure may be defined as: 1. For previously naïve patients or those with limited antiretroviral experience: Less than a one-log drop in viral load after 8-12 weeks therapy on a regimen.

2. For patients with more extensive antiretroviral experience: Less than a one-log drop in viral load after 6 months of continued treatment. 3. Repeated viral detection in plasma after initial suppression 4. A failure to increase CD4 count by 5% above the baseline or, for children over age of 4-6 years old, to increase their CD4 cell count by at least 50 cells/mm 3 above baseline over the first year of therapy. 5. Clinical deterioration: defined as progressive neurodevelopemental deterioration (i.e. the presence of two or more of the following findings documented on repeated assessments: impairment in brain growth, decline of cognitive function documented by psychometric testing, or clinical motor dysfunction), growth failure (i.e. persistent decline in weight-growth velocity despite adequate nutritional support and without other explanation), or severe or recurrent infection or illness (i.e. recurrence or persistence of AIDSdefining conditions or other serious infections). Recent (within 30 days or request or while patient was on current medication regimen) genotype and phenotype testing result was submitted with request for Fuzeon to determine optimal regimen of at least two sensitive and tolerated anti-retroviral medications and to eliminate previously ineffective anti-retroviral medications, or there are less than two effective medications based on sensitivity testing and the patient is at risk for opportunistic infection or death. The patient has a documented adherence level on taking anti-retroviral therapy of greater than 80% and any issue that may have caused a decrease in adherence in the past (difficulty of dosing schedule, etc.) has been addressed. If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-APPROVAL: Documentation of current background drug therapy (Fuzeon is not recommended as monotherapy or to be used without optimal oral therapy). For the initial reauthorization: documentation submitted of a viral load drop of > 0.7 log decrease from baseline after 12 weeks of starting therapy for requests to continue therapy beyond 16 weeks, or there is documentation provided that the patient has documented clinical improvement (i.e. increased CD 4 count) with treatment. After the initial reauthorization: documentation submitted of current (within the past 30 days) CD 4 count and HIV RNA viral load. If the patient has been on Fuzeon therapy AND there is an increase of at least 2 log in viral load or a 30% decline in CD4 counts from baseline then current phenotype/genotype testing (within the past 30 days) must be submitted to indicate continued susceptibility of the HIV virus to Fuzeon. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Fuzeon is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment experienced patients with HIV-1 replication depsite ongoing antiretroviral therapy. DOSAGE AND ADMINISTRATION: The recommended dose of Fuzeon is 90 mg (1mL) twice daily injected subcutaneously into the upper arm, anterior thigh, or abdomen. In pediatric patients 6 through 16 years of age, the recommended dosage of Fuzeon is 2mg/kg twice daily up to a maximum dose of 90mg twice daily injected subcutaneously into the upper arm, anterior thigh, or abdomen. Table 1: Generic (Brand; abbreviation) NRTIs NNRTIs PIs Fusion Inhibitors Entry Inhibitors CCR5 Co- Receptor Antagonists INSTIs Multi-Class Combinatins Zidovudine (RETROVIR ; AZT, ZDV) Nevirapine (VIRAMUNE ; NVP) Indinavir (CRIXIVAN ; IDV) Enfuvirtide (FUZEON ; T-20) Maraviroc (SELZENTRY ) Raltegravir (ISENTRESS ) Efavirenz, Emtricitabine and Tenofovir disoproxil fumarate (ATRIPLA Didanosine (VIDEX Delavirdine (RESCRIPTOR Ritonavir (NORVIR Dolutegravir (TIVICAY ) Emtricitabine, Rilpivirine, and Tenofovir

; ddi) ;DLV) ;RTV) ) disoproxil fumarate (COMPLERA Tenofovir disoproxil fumarate (VIREAD ; TDF) Efavirenz (SUSTIVA ; EFV) Nelfinavir (VIRACEPT, NFV) ) Elvitegravir, Cobicistat, Emtricitabine, Tenofovir disoproxil fumarate (STRIBILD ) Stavudine (ZERIT ; d4t) Etravirine (INTELENCE ) Saquinavir (INVIRASE ; SQV) Lamivudine (EPIVIR ; 3TC) Abacavir/La mivudine/zid ovudine (TRIZIVIR ) Lamivudine/ Zidovudine (COMBIVIR ) Tenofovir disproxil fumarate and Emtricitabine (TRUVADA ) Emtricitabine (EMTRIVA ) Rilpivirine (EDURANT ) Lopinavir and Ritonavir (KALETRA ; LPV/RTV) Tipranavir (APTIVUS ; APV) Fosamprenavir calcium (LEXIVA ; FOS-APV) REFERENCES: 1. www.aidsinfo.nih.gov. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. February 12, 2013. 2. www.aidsinfo.nih.gov. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV-Infected. November 11, 2012. 3. Lalezari J, Henry K, O Hearn M, et al. Enfuvirtide, and HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America. New England Journal of Medicine 2003. 4. CDC. MMWR 194; 43(No. RR-12): p. 1-10 5. www.righto.com/theories/aidsdef.html. 1997 CDC AIDS Definition. 6. www.paho.org. Pan American Health Organization (part of WHO). Case Definition-Acquired Immunodeficiency Syndrome (AIDS) 7. Fuzeon Prescribing Information, Genentech, Inc., 08/2012 Revision/Review Date: 01/2014 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

GILENYA (fingolimod hcl) capsules: 0.5mg FORMULARY STATUS: Non-formulary TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PA CRITERIA FOR INITIAL APPROVAL: The member is an adult ( 18 y/o) member with relapsing/remitting MS (RRMS) or secondary progressive MS (SPMS) with a relapsing element. Documentation must be submitted that the patient has had a documented treatment failure to three of the currently marketed Self-Injectable Disease-Modifying Immunomodulating MS Agent (see Box 1 in Glossary for definition of treatment failure) which is consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history, indicating they had received an adequate trial (including dates, doses of 6 months or more of each therapy) or has another documented clinically significant medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Copaxone and Rebif and then either Avonex, Betaseron, or Extavia for a minimum of 6 months each to treat their medical condition. The medication is being recommended or prescribed by a neurologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review REAUTHORIZATION CRITERIA: Documentation indicating the member has clinically benefited from therapy. The medication was prescribed at an FDA approved dosage. Medication was recommended by a neurologist or prescribed by a neurologist. If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review FDA INDICATIONS: Gilenya is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. DOSAGE AND ADMINISTRATION: The recommended dose of Gilenya of 0.5 mg orally once daily. Doses of higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits. BOX 1: TREATMENT FAILURE: A member may be considered to have failed treatment if any of the following are documented: 1. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** 2. Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** 3. Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** 4. Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** 5. Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** 6. Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** 7. Members who have new or enlarging T2 lesions, increase in brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities.** ** These are members who have a documented treatment failure after receiving a minimum of 6 months each of Copaxone and Rebif. Diagnostic or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that the member has failed a minimum of 6 months of (Copaxone and Rebif) or has a documented medical reason (i.e. intolerance) for not utilizing each of these therapies for a minimum of 6 months. Kurtzke Expanded Disability Status Scale (EDSS)

Rating Status 0 Normal Neurological Exam 1.0 No Disability, minimal symptoms 1.5 No disability, minimal signs in more than one area 2.0 Slightly more disability in one area 2.5 Slightly greater disability in two areas 3.0 Moderate disability in one area but still walking independently 3.5 Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. REFERENCES: 1. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relapsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/prc.asp 2. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/prc.asp 3. Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004; 63(Suppl 6):S33-S40. 4. Cohen JA, Barkhof F, Comi Giancarlo C. et al. Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. The New England Journal of Medicine.2010; 362: 402-15. 5. Kapps L, Antel J, Comi G. Et al. Oral Fingolimod (FTY720) for relapsing Multiple Sclerosis. The New England Journal of Medicine.2006; 355:1124-40. 6. Kappos L, Radue EW, O Connor P, Et al. A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis. The New England Journal of Medicine. 2010; 362: 387-401. 7. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. 8. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006; 245:111-116. 9. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. 10. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. 11. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. 12. Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon β: implications for clinical trials. Annals of Neurology. 2002;52:400-406. 13. Gilenya Prescribing Information. Novartis, Inc. 7/2011 14. Rosalind C. Kalb, Ph.D., Director, Professional Resource Center, National Multiple Sclerosis Society, MS Guidelines 11 August 2004, personal email (11 August, 2004). 15. Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology, Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 58(2):169-178, January 22, 2002. 16. Morrow T, Brown J, Smith C, Thrower B. Considerations for the treatment of multiple sclerosis in the managed care setting. Formulary 2003; 38 (11).

Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA GLEEVEC (imatinib): Tablets: 100mg, 400mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR PATIENTS WHO REQUIRE DAILY DOSES GREATER THAN 600MG/DAY FOR GLEEVEC FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA (CML): The patient has a documented clinical diagnosis of bcr--abl positive CML with either a lack of a complete hematologic response after 3 months of treatment with Gleevec, a lack of any cytogenetic response after 6 months of treatment with Gleevec, a lack of a cytogenetic response after 12 month of treatment with Gleevec, OR having relapsed after a hematologic response to Gleevec. Documentation (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) that the patient has received an adequate trial (including dates) at therapeutic doses of Sprycel (dasatinib) OR Tasigna (nilotinib). The medication is being prescribed at a dose that is within FDA approved guidelines or is supported by the medical compendium as defined by the Social Security Act or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of 12 months; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or the NCCN or ASCO standard of care guidelines. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6-month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or per the NCCN or ASCO standard of care guidelines. Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication If all of the above conditions are met, the request will be approved for up to a 6-month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical FDA APPROVED INDICATIONS and DOSAGE AND ADMINISTRATION: Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice daily. Treatment may be continued ad long as there is no evidence of disease progression or unacceptable toxicity.

Philadelphia positive Chronic Myeloid Leukemia (Ph+ CML): For newly diagnosed adult patients with Ph+ CML in the chronic phase the recommend starting dose is 400 mg/day Philadelphia positive Chronic Myeloid Leukemia (Ph+ CML) in Blast Crisis, Accelerated Phase, or Chronic Phase after interferonalpha therapy: For these adult patients the recommended starting dose is 600 mg/day Pediatric Patients with Philadelphia chromosome positive (Ph+) CML in Chronic Phase: the recommended dose of Gleevec for children with newly diagnosed Ph+ CML is 340 mg/m 2 /day (not to exceed 600 mg). For pediatric patients who disease is recurrent after stem cell transplantation or are resistant to interferon-alpha therapy the recommended starting dose is 260 mg/m 2 /day of Gleevec Gastrointestinal Stromal Tumors (GIST): 400mg/day or 600mg/day for adult patients with Kit (CD117) positive unresectable or metastatic, malignant GIST Adjuvant Treatment of Gastrointestinal Stromal Tumors (GIST): 400 mg/day for adult patients following the complete gross resection of GIST. Myelodysplastic/Myeloproliferative Disease (MDS/MPD): For adult patients with MDS/MPD associated with PDGFR (plateletderived growth factor) gene rearrangement the recommended dose of Gleevec is 400 mg/day. Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL): For adult patients with relapsed or refractory Ph+ ALL the recommended dose of Gleevec is 600mg/day. Aggressive Systemic Mastocytosis (ASM): For adult patients with ASM with the D816V c-kit mutation or with c-kit mutational status unknown then the recommended dose of Gleevec is 400 mg/day. Dermatofibrosarcoma Protuberans (DFSP): For adult patients with unresectable, recurrent, or metastatic DFSP the recommended dose of Gleevec is 800 mg/day. Hypereosinophilic Syndrome (HES) or Chronic Eosinophilic Leukemia (CEL): The recommended dose of Gleevec is 400 mg/day for adult patients with HES/CEL. For patients with demonstrated F1P1L1-PDGFRα fusion kinase, a starting dose of 100 mg/day is recommended. DOSE ADJUSTMENTS: Dose adjustments for Hepatic Impairment: Patients with mild and moderate hepatic impairment do not require a dose adjustment and should be treated per the recommended dosing guidelines. Patients with severe hepatic impairment recommended dose should be decreased by 25%. Dose adjustments for Hepatotoxicity and Non-Hematologic Adverse Reactions: If the patient s bilirubin has elevated >3x institutional upper limit of normal (IULN) or the liver transaminases has >5 x IULN, then Gleevec should be withheld until the bilirubin levels have returned to a level of <1.5 x IULN and transaminases level of <2.5 x IULN. At this point, treatment can be restarted at a lower dose. If a severe non-hematologic adverse reaction (i.e. severe fluid retention) occurs treatment should be held until the event has resolved and then can resume at an appropriated dosing depending on the initial severity of the event. When using when using concomitant CYP3A4 inhibitor/inducer therapy: (i.e. dexamethasone, phenytoin, carbamazepine, phenobarbital, rifamycins and St. John s wart). The concomitant use of a strong CYP3A4 inducer should be avoided. However if the patient should be given a strong CYP3A4 inducer then the dosage of Gleevec should be increased by at least 50% and clinical response should be carefully monitored. REFERENCES: 1. NCCN Clinical Practice Guidelines in Oncology : Chronic Myelogenous Leukemia, V.2.2010 2. Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatibib: a randomized phase 2 trial. Blood 2007; 109: 5143-50. 3. Zonder JA, Pemberton P, Brandt H, et al. The Effect of Dose Increase of Imatinib Mesylate in Patients with Chronic or Accelerated Phase Chronic Myelogenous Leukemia with Inadequate Hematologic or Cytogenetic Response to Initial Treatment. Clinical Cancer Research 2003; 9: 2092-97. 4. Gleevec Prescribing Information, Novaratis, 4/2011 Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION PROTOCOL FOR GONADOTROPIN RELEASING HORMONE AGONISTS (GnRH) Eligard 7.5 mg, 22.5 mg, 30 mg, and 45 mg Firmagon : 80mg and 120mg vial Leuprolide Acetate (Lupron ) injection 5 mg/ml (2.8 ml) Lupron Depot : 3.75 mg, 7.5 mg Lupron Depot -3 Month: 11.25 mg, 22.5 mg Lupron Depot -4 Month: 30 mg Lupron Depot-Ped : 7.5 mg, 11.25 mg, 15 mg Supprelin LA 50 mg Trelstar : 3.75mg, 11.25mg, 22.5mg Vantas Implant 50 mg Zoladex 3.6 mg and 10.8 mg Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, Drug Package Insert) as defined in the Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), The American College of Obstetricians and Gynecologists (ACOG), or the American Academy of Pediatrics (AAP) standard of care guidelines. If the medication request is for any other GnRH agonist other than Lupron, the patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) treatment failure after receiving an adequate trial (including dates of 3 months or more of therapy) of Lupron and/or has another documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing Lupron to treat their medical condition. If the medication request is for the treatment of a confirmed diagnosis of endometriosis, the patient is an adult female ( 18 y/o) who does not have documented Osteoporosis. If the medication request is for the treatment of fibroids, the patient is an adult female ( 18 y/o) and ONE of the following apply to the patient: 1. The patient is anemic (Hgb < 10.2 g/dl or Hct of < 30%) attributed to fibroids and the patient has had a one to three month trial of iron therapy alone which is (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) to try and correct the anemia or there is a medical reason (intolerance, hypersensitivity, contraindication, etc) for not using iron alone to manage the anemia. 2. The patient requires the medication to decrease uterine volume as a result of uterine fibroids to manage symptoms (i.e. pelvic pressure, pelvic fullness, urinary frequency, nocturia, constipation and/or anemia) and for shrinkage of size to allow surgical intervention. If the medication request is for the treatment of endometrial thinning, documentation was submitted indicating the patient is scheduled for endometrial ablation for dysfunctional uterine bleeding. If the medication request is for the treatment of central precocious puberty (CPP), there is a clinical diagnosis of CPP with onset of secondary sexual characteristics less than age 8 in females and age 9 in males and ALL of the following apply to the patient: 1. Diagnosis is confirmed by a pubertal response to a GnRH stimulation test, bone age advanced 1 year beyond chronicle age. 2. There are documented baseline evaluations (including ultrasound, CT, MRI, and laboratory levels) to rule out a tumor. Prescribed dosing of GnRH agonist is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines. The medication is recommended and prescribed by a specialist in the field to treat the patient s respective medical condition

If all of the above conditions are met, the request will be approved for up to 6 months for treatment of prostate cancer or central precocious puberty and up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines. If the medication reauthorization is for endometriosis ALL of the following apply to the patient: 1. If the request is for a continuation of treatment exceeding 6 months, the patient is receiving or will be prescribed add back hormonal therapy (norethindrone acetate 5 mg daily or conjugated estrogen therapy) {consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history}, OR if the patient has a documented medical reason for not being able to take add back therapy, the patient is receiving or is intended to receive anti-osteoporosis therapy (e.g. alendronate or risedronate) {consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history}. 2. If the patient received > 6 to 11 months cumulative doses of the GnRH agonist a Dexa scan was performed and the results were submitted with the medication request, indicating that the patient does not have documented Osteoporosis AND the patient is receiving calcium supplementation (1200 mg/day) and vitamin D (400-800 units/day), which is (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history). 3. The patient has not received cumulative doses of the GnRH agonist up to or greater than 12 months of therapy. If the medication reauthorization is for fibroids, the patient has not received cumulative doses of the GnRH agonist up to or greater than 6 months of therapy. If the medication reauthorization is for central precocious puberty, the child is male and < 12 years or female and < 11 years of age OR the child is male and is > 12 years of age or a female that is > 11 years of age, and has an acceptable documented medical reason to continue treatment. The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 6 months for treatment of prostate cancer or central precocious puberty and up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, ACOG or AAP standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA APPROVED INDICATIONS and DOSAGE AND ADMINISTRATION: Lupron, Lupron Depot, Lupron Depot-Ped : Endometriosis (decrease pain/lesions): 11.25mg IM Q 3months x 6 months; 3.75mg IM Q month x 6 months Premenstrual Dysphoric Disorder: 3.75 mg IM once a month x 3months Advanced Prostate Cancer-palliative treatment: 1mg SC once a Day (available generically); 22.5mg IM Q3months, 30mg IM Q4months; 7.5mg IM once a month Uterine Leiomyoma (Fibroids): 11.25mg IM 3 months depot x 1; 3.75mg IM once a month x 3mos Central Precocious Puberty (CPP): For injection: 50mcg/kg/day SC x 1 dose, if down regulation is not achieved, repeat by titrating dose up by 10mcg/kg/day to final titrated maintenance dose. May be administered by a patient/parent or health care professional; For depot: give 300mcg/kg (Min dose 7.5mg) IM Q4 wks as

depot x 1 injection, if down regulation is not achieved, repeat by titrating dose up by 3.75mg Q4wks, the final titrated dose is the maintenance dose). Must be administered under physician supervision. Weight (kg) Leuprolide Depot Starting Dose for CPP Dose (mg) 25 7.5 > 25 to 37.5 11.25 > 37.5 15 Chronic Pelvic Pain: 3.75mg IM Q4wks x 3 months Prostate Cancer, Neoadjuvant Tx: 7.5mg IM once a month plus flutamide TID PO x 3-8months Breast Cancer: 3.75mg IM once a month; 11.25mg IM Q3months Eligard Advanced Prostate Cancer-palliative care: 7.5mg SC once a month; 22.5mg SC Q3months; 30mg SC Q4months; 45mg SC Q6months Firmagon Advanced Prostate Cancer: 240mg given once (as two injections of 120mg each) followed by a single 80mg injection once every 28 days. Zoladex Advanced Breast Cancer: 3.6mg SC Q28 days long term Endometriosis (decrease pain/lesions): 3.6mg SC Q28 days x 6months Endometrial Thinning: 3.6mg SC 4 wks prior to ablation surgery; 3.6mg SC given 4 wks apart w/2 nd inject given 2-4wks before ablation Advanced Prostate Cancer- palliative care: 3.6mg SC Q28 days OR 10.8mg SC Q3mos Prostate Cancer-stageB2-C local: 3.6mg SC then in 28days 10.8mg SC 8 wks prior to XRT in combination with flutamide OR 3.6mg Q28 days x 4 (2 prior/2 during XRT) Trelstar Advanced Prostate Cancer - palliative care: 3.75mg IM every 4 weeks, 11.25mg IM every 12 weeks, 22.5mg IM every 24 weeks Vantus Implant Advanced Prostate Cancer- palliative care: 50mg SC Q12 months Supprelin LA Central precocious puberty: 1 implant (50mg) every 12 months. 1 implant (50mg) SC every 12 months. Remove after 12 months * Note: Use of these medications to promote fertility, is not a covered benefit under the Medical Assistance Program, except when prescribed for certain diagnosis, such as regulation of menstrual cycle. References: 1. The American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Medical management of endometriosis. International Journal of Gynecology & Obstetrics. 2000;71:183-196. Bulletin Number 11, December 1999 (Replaces Technical Bulletin Number 184, September 1993. 2. The American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. Committee Opinion: Endometriosis in Adolescents. Obstetrics & Gynecology. 2005;105:921-927. ACOG Committee Opinion Number 310, April 2005. 3. Kohn B. Julius JR. Blethen SL. Combined use of growth hormone and gonadotropin-releasing hormone analogues: the National Cooperative Growth Study Experience. National Cooperative Growth Study: Guidance in Growth: Proceedings of the National Cooperative Growth Study Twelfth Annual Investigators Meeting in New Orleans, LA. 4. Walvord EC. Pescovitz OH. Combined use of growth hormone and gonadotropin-releasing hormone analogues in precocious puberty: theoretic and practical considerations. National Cooperative Growth Study: Guidance in Growth: Proceedings of the National Cooperative Growth Study Twelfth Annual Investigators Meeting in New Orleans, LA. American Academy of Pediatrics. 1999;104(4)Supplement to Pediatrics, Part2 of 2:1010-1014. 5. Elders MJ. Scott CR. Frindik JP. Kemp SF. Clinical workup of precocious puberty. The Lancet.1997;350(9076):457-458. 6. Kaplowitz PB. Oberfield SE. The Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Special Article. The American Academy of Pediatrics. Pediatrics. 1999;104(4, Part 1 of 2): 936-941. 7. Hall MC. Fritzsch RJ. Sagalowsky AI. Et al. Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer. Urology. 1999:53(5):898-902. 8. Kimura K. Markowski M. Bowen C. Gelmann EP. Androgen blocks apoptosis of hormone-dependent prostate cancer cells. Cancer Research.2001;61:5611-5618. 9. Shahidi M. Norman AR. Gadd J. et al. Recovery of serum testosterone, LH and FSH levels following neoadjuvant hormone cytoreduction and radical radiotherapy in localized prostate cancer. Clinical Oncology. 2001;13:291-295.

10. Seidenfeld J. Samson DJ. Hasselblad V. et al. Single therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Annals of Internal Medicine.2000;132:566-577. 11. Lupron Injection, Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. November 2006. 12. Lupron Depot 3.75mg Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. October 2005. 13. Lupron Depot 7.5mg Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. November 2006. Lupron Depot-Ped. TAP Pharmaceuticals Inc. Lake Forest, IL. December 2007 14. Lupron Depot - 3 month 11.25mg Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. December 2007. 15. Lupron Depot - 3 month 22.5mg Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. December 2010. 16. Lupron Depot - 4 month 30mg Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. December 2007. 17. Lupron Depot - PED Package Insert. TAP Pharmaceutical Products, Inc. Forest, IL. December 2007. 18. Firmagon Package Insert. Ferring Pharmaceuticals. Parsippany, NJ. February 2009. 19. Eligard Package Insert. Sanofi-Aventis. Fort Collins, CO. October 2010. 20. Zoladex 3.6 mg and 10.8mg. Package Insert. Astra Zeneca. Wilmington, DE. December 2010. 21. Trelstar Package Insert. Watson Pharma, Inc. Corona, CA. January 2011. 22. Vantus Package Insert. Indevus Pharmaceuticals, Inc. Lexington, MA. February 2011. 23. Supprelin Package Insert. Endo Pharmaceuticals, Inc. Chadds Ford, PA September 2010. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

AMERIHEALTH CARITAS SOUTHERN REGION HEPATITIS C TREATMENT GUIDELINES Updated May 21, 2014 INSTRUCTIONS: 1. Review the posted Hepatitis C Treatment Guidelines document to validate that your patient meets the criteria for treatment. 2. Complete the online Hepatitis C Prior Authorization Form in its entirety. 3. Print, Sign and fax the completed Prior Authorization Form along with copies of laboratory results, required documentation from medical record, and all other supporting information to: PerformRx at 855 516 6384

DRUGS PREFERRED PEGINTRON (peginterferon alfa 2b): 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL powder for injection in Redipens or glass vials COPEGUS (ribavirin): 200mg tablet REBETOL (ribavirin): 200mg capsule SOVALDI (sofosbuvir): 400mg tablets OLYSIO (simeprivir): 375mg capsules DRUGS NOT PREFERRED PEGASYS (peginterferon alfa 2a): 180mcg/ml single use glass vials or prefilled syringe INCIVEK (telaprivir): 375mg tablets VICTRELIS (boceprevir): 200mg capsules All Initial requests MUST meet the following requirements: 1. Patient Age 18 or older, AND 2. Medical history: Past medical history and co morbidities Complications of chronic liver disease Symptoms, AND 3. Psychiatric history: Psychiatric disorders, past and present Substance abuse (if there is a history of substance abuse, an attestation that the patient is drug and alcohol free) Conditions affecting compliance, AND 4. Lab testing within three (3) months of starting treatment (copy of results required): ALT/AST, albumin, bilirubin, total and direct, prothrombin time Genotype HCV RNA viral load CBC, ferritin, iron saturation TSH, ANA Serum creatinine, glucose, uric acid ECG, echocardiogram, stress test in the presence of heart disease 5. Lab testing within one (1) month of starting treatment (copy of results required): Urine drug screen Blood alcohol level Pregnancy test in women of childbearing age, with patient agreeing to use two or more forms of contraception, and will have monthly pregnancy tests during therapy, AND 2

6. Serum HBsAg, anti HBc, anti HBs, anti HAV, AND 7. HIV serology (CD4+ T cell count and HIV RNA are required for patients co infected with HIV, AND In patients with lower CD4 counts (e.g., <200 cells/mm3), it may be preferable to delay HCV therapy until CD4 counts increase) 8. The patient has had a Liver biopsy showing advanced to severe fibrosis. Either Ishak Stage >3 or Metavir Score >2, AND Ishak stage > 3 Ishak Staging Scale Fibrous Category measurement Histologic descripton 0 1.9% No fibrosis 1 3.0% Fibrous expansion of some portal areas (+/ ) short fibrous septa 2 3.6% Fibrous expansion of most portal areas (+/ ) short fibrous septa 3 6.5% Fibrous expansion of some portal areas with occasional portal to portal (P P)bridging 4 13.7% Fibrous expansion of portal areas with marked P P and portal to central (P C) bridging 5 24.3% Marked P P and/or P C bridging with occasional nodules 6 27.8% Cirrhosis, probable or definite Stage 1 Stage 2 Stage 3 Stage 4 Metavir score > 2 Metavir Fibrosis Classification Portal / periportal fibrosis Septal fibrosis Bridging fibrosis with architectural distortion Cirrhosis, probable cirrhosis 9. Patient is sofosbuvir treatment naïve (no claims history or reference in medical records to previous trial and failure of sofosbuvir), AND 10. The dose that has been prescribed for the patient is consistent with the dosing recommendations listed below, and the prescriber is a hepatologist / gastroenterologist / infectious disease specialist/transplant specialist, AND 11. For a pegylated interferon alpha product, PegIntron is the preferred agent 12. Presence of previous treatment, treatment regimen and response Treatment Naïve / Previous Relapsed Previous Partial Responders / Null Responders 3

APPROVAL CONSIDERATIONS: Compliance: 1. A nurse case manager will reach out to all members approved for treatment, with the intent to educate and ensure successful completion of the regimen. 2. The nurse case manager will guide and reinforce compliance through ongoing interaction with the member. 3. Demonstrated non compliance with the treatment regimen, defined as two consecutive missed doses or more than four missed doses in a four week period, renders the treatment ineffective and may result in denial of additional authorizations. In the presence of previous substance abuse (including alcohol and prescription drugs), ALL: 1. No alcohol or illicit drug use within 6 months of treatment onset, AND 2. Negative drug and / or blood alcohol level 30 days prior to treatment onset, AND 3. Physician attestation of patient abstinence from drugs and alcohol, and is compliant with treatment program participation as documented by a copy of the note in the patient s medical record. The presence of ANY of the following excludes approval: 1. Severe or uncontrolled co morbidities 2. Sever renal impairment or End Stage Renal Disease (ESRD) 3. Transplant (except liver) 4. Disorders of mood, thought, or cognition expected to negatively impact treatment compliance 5. Substance abuse (positive urine drug screen or blood alcohol level) 6. Less than severe fibrosis on biopsy 7. Contraindication to any component of the treatment regimen Contraindications to treatment with interferon: 1. A baseline neutrophil count below 1500/uL, a baseline Platelet count below 90,000/uL or baseline hemoglobin below 10g/dL 2. Intolerance to IFN 3. Autoimmune Hepatitis and other autoimmune disorders 4. Hypersensitivity to PEG or any of its components 5. Decompensated Hepatic disease 6. History of depression or clinical features consistent with depression 7. History of preexisting cardiac disease 8. Transplant of kidney, heart, or other solid organ (excluding liver transplant). 4

Contraindications to treatment with ribavirin: 1. Hypersensitivity to drug, class, or components 2. Autoimmune hepatitis 3. GFR < 50 4. Pregnancy 5. Hemoglobinopathy Contraindications to treatment with Sovaldi: 1. Hypersensitivity to drug, class, or components 2. HCV monotherapy 3. Significant drug drug interactions Contraindications to treatment with Olysio: 1. Hypersensitivity to drug, class, or components 2. HCV monotherapy 3. Significant drug drug interactions WHEN CRITERIA FOR APPROVAL FOR THE TREATMENT OF HEPATITIS C INFECTION IS MET**: The patient will be placed into one of the following categories: Hepatitis C Genotype 1 infection: Go to section I Hepatitis C Genotype 2 infection: Go to section II Hepatitis C Genotype 3 infection: Go to section III Hepatitis C Genotype 4 infection: Go to section IV Hepatitis C Genotypes 5 and 6 infections: Go to section V Hepatitis C Genotypes 1, 2, 3, or 4 infections with Hepatocellular Carcinoma with Ribavirin and Sovaldi: Go to section VI **These treatment regimens are for patients that are treatment naïve, relapser with Pegylated interferon and Ribavirin, or coinfected with HIV. For partial responders or null responders, please refer to the most current dosing guidelines. 5

Section I: Treatment for patients with Hepatitis C Genotype 1 infection: Interferon eligible patients: Approve Sovaldi 400mg tablet #28 for 28 days with Ribavirin and Pegylated Interferon for a total of 12 weeks. Interferon ineligible patients: Approve Sovaldi 400mg tablet #28 tablets for 28 day supply with Olysio #28 for 28 day supply for a total of 12 weeks. Section II: Treatment for patients with Hepatitis C Genotype 2 infection: Approve Sovaldi 400mg tablet #28 tablets for a 28 day supply with Ribavirin for 12 weeks. Section III: Treatment for patients with Hepatitis C Genotypes 3 infection: Interferon eligible patients: Approve Sovaldi 400mg tablet #28 for a 28 day supply with Ribavirin and Pegylated Interferon for a total of 12 weeks. Interferon ineligible patients: Approve Sovaldi 400mg tablet #28 tablets for 28 day supply with Ribavirin for a total of 24 weeks. Section IV: Treatment for patients with Hepatitis C Genotype 4 infection: Interferon eligible patients: Approve Sovaldi 400mg tablet #28 for 28 days with Ribavirin and Pegylated Interferon for a total of 12 weeks. Interferon ineligible patients: Approve Sovaldi 400mg tablet #28 for 28 days with Ribavirin for a total of 24 weeks. Section V: Treatment for patients with Hepatitis C Genotypes 5 or 6 infections with Ribavirin and Sovaldi: Approve Sovaldi 400mg tablet #28 for 28 days with Ribavirin and Pegylated Interferon for a total of 12 weeks. Per AASLD guidelines: No data are available to support the use of a non PEG containing regimen for patients with HCV genotype 5 or 6 infection. Section VI: Treatment for patients with Hepatitis C Genotypes 1, 2, 3, or 4 infections with Hepatocellular Carcinoma with Ribavirin and Sovaldi: All initial requests must meet the following additional requirement: Documentation of testing confirming the diagnosis of Hepatocellular Carcinoma through either Imaging Testing (such as Ultrasound, Computed Tomography, Magnetic Resonance Imaging), Laparoscopy, or Biopsy. Approve Ribavirin and Sovaldi for 24 weeks (Sovaldi 400mg tablet #28 tablets for a 28 day supply with five refills). o The patient may be approved for an additional 24 weeks after receiving confirmation the patient has not yet received a transplant. o If the patient has received a transplant, treatment is stopped. Deny with the appropriate rationale. 6

REFILL CONSIDERATIONS: Demonstrated non compliance with the treatment regimen, defined as two (2) consecutive missed doses or more than four (4) missed doses in a four week period, renders the treatment ineffective and may result in denial of additional authorizations Evidence of substance abuse may result in denial of additional authorizations Failure to submit follow up pregnancy result for patient of child bearing age every 30 days, or a result demonstrating pregnancy may result in denial of additional authorizations REFERENCES: 1. Yee HS. Currie SL. Darling JM. Et al. Management and treatment of hepatitis C viral infection: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Practice Guidelines. American Journal of Gastroenterology. 2006;101:2360 2378. 2. National Institutes of Health. Chronic Hepatitis C: Current Disease Management. National Institute of Diabetes and Digestive and Kidney Diseases. U.S. Department of Health and Human Services. Available at: http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/chronichepc.pdf. Last updated November 2006. Accessed May 9, 2007. 3. Ghany MG, Strader DB, Thomas DL, Seef LB. Diagnosis, management and treatment of Hepatitis C: An Update. American Association for the Study of Liver Diseases Practice Guideline. Hepatology. 2008; 49(4): 1335 74. 4. Lok ASF. McMahon BJ. Chronic Hepatitis B. American Association for the Study of Liver Diseases Practice Guidelines. Hepatology. 2007;45(2):507 539. 5. NIH Consensus Development Program: National Institutes Health Consensus Conference Statement June 10 12, 2002. Management of Hepatitis C. guidelines. Available from URL: http://consensus.nih.gov/cons/116/hepc091202.pdf. 6. Department of Veterans Affairs. A Supplement to Federal Practitioner. VA recommendations version 5.0. Patients with chronic Hepatitis C. 2003;20(5):1 33. 7. Alberti A. Clumeck N. Collins S. et al. Short statement of the first European Consensus Conference on the treatment of chronic Hepatitis C and B in HIV Co infected patients. March 1 2, 2005. Paris, France. Published in the Journal of Hepatology in May 2005. Available at http://www.hivandhepatits.com. Accessed May 14, 2007. 8. Soriano V. Highlights of the 2nd International Workshop on HIV and Hepatitis Co infection. January 12 14, 2006. Amsterdam, The Netherlands. Medscape HIV/AIDS. 2006;12(1). Available at http://www.medscape.com. Accessed May 14, 2007. 9. Soriano V. Puoti M. Sulkowski M. et al. Care of patients with Hepatitis C and HIV co infection. AIDS. 2004;18:1 12. 10. Swan T. Raymond D. Sherman KE. Et al. Hepatitis C Virus and HIV/HCV Co infection. A critical review of research and treatment. Treatment Action Group (TAG). July 2004. Available at: http://www.aidsinfonyc.org/tag/coinf/hcv2004. Accessed May 14, 2007. 11. Department of Veterans Affairs. Hepatitis C Resource Centers. Management and treatment of Hepatitis C virus infection in HIV infected adults: Recommendation from the Veterans Affairs Hepatitis C Resource Center Program and National Hepatitis C Program Office. American Journal of Gastroenterology. 2005;100(10):2338 2354. Also available online at: http://www.hepatitis.va.gov/pdf/va01 pr/prtop 06/2005_coinf_recs.pdf. Accessed May 14, 2007. 12. Pegasys and Copegus package information. Roche Pharmaceuticals. June 2010. 13. PegIntron and Rebetrol package information. Schering Corporation. January 2010. 14. Victrelis prescribing information. Schering Corporation. May 2011. 15. Incivek prescribing information. Vertex Pharmaceuticals Inc. May 2011. 16. Yee HS. Chang MF. Christine P. Et al. Update on the Management and Treatment of Hepatitis C Virus Infection: Recommendations from the Department of Veteran Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Practice Guidelines. American Journal of Gastroenterology. 2012: 107: 669 689. 7

17. Sovaldi (package insert). Foster City, California: Gilead Corporation 12/2013. Accessed through: http://www.gilead.com/~/media/files/pdfs/medicines/liver disease/sovaldi/sovaldi_pi.pdf 18. Olysio (package insert). Titusville, New Jersey: Janssen Therapeutics 12/2013. 19. American Association for The Study of Liver Diseases Treatment Guidelines: Accessed through: http://www.hcvguidelines.org/full report/initial treatment hcv infection patients starting treatment Revision/Review Date: 6/22/2014 8

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FOR GROWTH HORMONE GENOTROPIN CARTRIDGE 5mg/vial, 12 mg/vial GENOTROPIN MINIQUICK 0.2mg/vial, 0.4mg/vial, 0.6mg/vial, 0.8mg/vial, 1.0mg/vial, 1.2mg/vial, 1.4mg/vial, 1.6mg/vial, 1.8mg/vial, and 2.0mg/vial HUMATROPE 5mg/vial HUMATROPE CARTRIDGE 6mg/cartridge, 12mg/cartridge, 24mg/cartridge NORDITROPIN FLEXPRO 5mg/1.5ml, 10mg/1.5ml, 15mg/1.5ml NORDITROPIN NORDIFLEX 30mg/3ml OMNITROPE 5.8mg/vial NUTROPIN 10mg/vial NUTROPIN AQ 10mg/2ml NUTROPIN AQ PEN 10mg/2ml, 20mg/2ml NUTROPIN AQ NUSPIN 5mg/2ml, 10mg/2ml, 20mg/2ml SAIZEN 5mg/vial, 8.8mg/vial, 8.8mg/cartridge TEV-TROPIN 5mg/vial PA CRITERIA FOR APPROVAL: The physician has written for a FDA approved indication or other medically accepted use as per compendia (DrugPoints, Micromedex, American Hospital Formulary System, Package Insert) excluding the use for cosmetic purposes PLEASE NOTE: The use of a Growth Hormone product to treat idiopathic short stature (ISS) is considered a cosmetic use and is not a covered benefit and will not be approved. AND For patients with growth hormone deficiency states (adult and pediatric) either the appropriate information, diagnosis &/or laboratory information has been provided with the request. This includes Growth Hormone (GH) level in response to the preferred stimulatory test (i.e. Insulin Tolerance Test or Glucagon or Arginine) &/or Insulin Growth Factor 1 level indicative of GH deficiency. In addition, for pediatric patients, documentation of his or her growth velocity (below 4.5 cm/year), their height percentile for age and gender, how far below the standard deviation (SD) their height is for their age (at least 2 SD below normal), or how far below the SD their height is from their mid-parent height percentile (at least 2 SD below). Please see the table below for additional information on neonatal GHD. Please see table below for additional information. AND The medication is recommended and prescribed by an endocrinologist AND The medication is being prescribed at an appropriate dose AND If the patient is 17 years of age or older and was diagnosed with childhood onset growth hormone deficiency, documentation was provided that indicates GH therapy is still medically necessary despite a 1-3 month trial off the medication (GH therapy discontinued for 1-3 months and resulting GH/IGF-1 levels are low). AND If the patient is 17 years of age or older and still requires GH therapy and is receiving childhood dosing versus lower adult dosing, appropriate documentation was provided (i.e. patient has not reached maximum predicted height or is still having clinical response) documenting the medical necessity of childhood GH dosing. AND If the request is not for Humatrope brand growth hormone, the provider submitted a documented medical reason (i.e. intolerance) why it is medically necessary to utilize some other brand formulation (Genotropin, Norditropin, Nutropin, Omnitrope etc.) of Growth Hormone. If all of the above conditions are met, the initial request will be approved with a 6-month duration and requests for reauthorization will be approved for a 12 month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. DIAGONOSIS AND TESTING INFORMATION:

Diagnosis Information Required Growth Hormone Testing Required Turner s Syndrome, Prader-Willi Syndrome, & Noonan Syndrome Neonatal Growth Hormone Deficiency Children with Chronic Renal Insufficiency Children who are Small for Gestation Age (SGA) Documented short statue for age and sex. For patients with Prade- Willi Syndrome, documentation that the patient does not have upper airway obstruction, sleep apnea, or severe resipiratory impairment. Insulin-like growth factorbinding protein (IGFBP) 3 is of value for diagnosing GHD in infancy. In addition, patients may present with neonatal hypoglycemia in the absence of a metabolic disorder. Documented short statue for age and sex. For patients with short statue or growth failure associated with chronic renal insufficiency in patients with chronic renal failure or end-state renal disease up to the time of renal transplantation. Documented short statue for age and sex. The patients is at least 2 years old and documentation of the patient s birth weight being less than 2500 g at a gestational age of 37 weeks or more OR a birth weight or length below the 3 rd percentile for gestational age N/A N/A N/A MEDICALLY ACCEPTED INDICATIONS: ADULTS For the replacement of endogenous growth hormone in adults with growth hormone deficiency who meet either of the following 2 criteria: Adult onset: Patients who have growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. Childhood onset: Patients who were growth hormone deficient during childhood as a result of congenital, genetic, acquired, or idiopathic causes. CHILDREN: Growth failure due to an inadequate secretion of endogenous growth hormone. Growth failure due to Prader-Willi syndrome. Confirm the diagnosis of Prader-Willi syndrome by appropriate genetic testing (Genotropin & Omnitrope Only). Growth failure in children born small for gestational age who fail to manifest catch-up growth by 2 years of age. Growth failure associated with Noonan syndrome and Turner syndrome in patients who have open epiphyses. For the treatment of idiopathic short stature, also called non growth-hormone-deficient short stature, defined by height standard deviation score less than or equal to 2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, in children whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means. For the treatment of growth failure associated with chronic renal function impairment up to the time of renal transplantation. For the treatment of short stature or growth failure in children with short stature homeobox-containing gene (SHOX) deficiency whose epiphyses are not closed DOSAGE AND ADMINISTRATION: ADULTS: up to 0.15-0.30 mg/day or up to 0.0125 mg/kg/day

CHILDREN: Chronic renal insufficiency (CRI): up to 0.35 mg/kg/week divided into daily SC injections is recommended. Therapy may be continued up to the time of renal transplantation. Growth Hormone deficiency: up to 0.3mg/kg/week Noonan s Syndrome: up to 0.066 mg/kg/day Prader-Willi syndrome: up to 0.24mg/kg/week Short for gestational age: up to 0.48mg/kg/week Turner syndrome: up to 0.375 mg/kg/week (1.125 IU/kg) of body weight administered by SC injection is recommended. Divide into equal doses given either daily or on 3 alternate days. REFERENCES: 1. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Growth Hormone Use in Adults and Children- 2009 Update. Endocrine Practice Vol 15 (Suppl 2) September/October 2009. 2. Facts and Comparisons. Growth Hormone Product information, 2002 3. Genotropin Package Insert. Pharmacia & Upjohn Co, Pfizer Inc. New York, NY, 02/2012. 4. Humatrope Package Insert. Eli Lilly and Company. Indianapolis, IN. 08/2011. 5. Norditropin Package Insert. Novo Nordisk Inc. Princeton, NJ. 05/2011. 6. Nutropin Package Insert. Genetech Inc. San Francisco, CA. 04/2012. 7. Omnitrope Package Insert. Sandoz Inc. Princeton, NJ. 10/2011. 8. Saizen Package Insert. EMD Serono Inc. Rockland, MA. 04/2012. 9. Tev-Tropin Package Insert. Gate Pharmaceuticals. Sellersville, PA. 07/2011. Revision/Review Date: 01/2014 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA HEPSERA (adefovir) Tablet: 10mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of hepatitis B. AND Submitted current laboratory values indicating evidence of active viral replication. AND Submitted current laboratory values indicating persistent elevations in ALT or AST or histologically active disease. AND Documented treatment failure with or contraindication to Baraclude therapy. AND Patient under the care of a gastroenterologist. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Chronic hepatitis B: Treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function. For patients 12 to <18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg+ chronic hepatitis B virus infection with compensated liver function. DOSAGE AND ADMINISTRATION: The recommended dose of adefovir in chronic hepatitis B patients with adequate renal function is 10 mg once daily taken orally without regard to food. The optimal duration of treatment is unknown. Dose adjustment in renal impairment: Adjust the dosing interval of adefovir in patients with baseline creatinine clearance (Ccr) less than 50 ml/min using the following suggested guidelines. Dosing Interval Adjustment of Adefovir in Patients with Renal Impairment Ccr (ml/min): Creatinine Clearance (ml/min) Hemodialysis 50 30-49 10-29 Patients Recommended dose 10 mg every 24 10 mg every 48 10 mg every 72 10 mg every 7 days and dosing interval hours hours hours following dialysis BLACK BOX WARNING: Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B therapy, including therapy with adefovir dipivoxil. Closely monitor hepatic function in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted. In patients at risk of or having underlying renal dysfunction, chronic administration of adefovir dipivoxil may result in nephrotoxicity. Closely monitor these patients for renal function and adjust dose as required. Human Immunodeficiency Virus (HIV) resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with anti-hepatitis B therapies, such as therapy with adefovir dipivoxil that may have activity against HIV. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals. REFERENCES: 1. Papatheodoridis GV, Hadziyannis SJ. Current management of chronic hepatitis b. Aliment Pharmacol Ther 2004; 19(1):25-37 2. Leung N. Nucleoside analogues in the treatment of chronic hepatitis B.J Gastroenterol Hepatol (Australia), May 2000, 15 Suppl pe53-60

3. Skowron G, Kuritzkes DR, Thompson MA, et al.once-daily quadruple-drug therapy with adefovir ipivoxil, Lamivudine, Didanosine, and efavirenz in treatment-naive human immunodeficiency virus type 1-infected patients.j Infect Dis (United States), Oct 1 2002, 186(7) p1028-33 4. Yang H, Westland CE, Delaney WE, et al.resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks.hepatology (United States), Aug 2002, 36(2) p464-73 5. Davis GL Update on the management of chronic hepatitis B. Rev Gastroenterol Disord (United States), Summer 2002, 2(3) p106-15 6. Facts and Comparisons, St. Louis, efacts. 2010 CliniSphere Version ISBN 1-57439-036-8 7. Hepsera Prescribing Information. Gilead Sciences, Inc. October 2009. 8. Lok ASF, McMahon BJ. American Association for the Study of Liver Diseases Practice Guidelines - Chronic hepatitis B: update 2009. Hepatology 2009;50(3):1-36. 9. Emmet BK, Dieterich DT, Han SHB, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clinical Gastroenterology and Hepatology 2008;6:1315-41. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA HERCEPTIN (TRASTUZUMAB): 440mg/vial lyophilized powder for injection PA CRITERIA FOR INITIAL APPROVAL FOR BREAST CANCER: Diagnosis of advanced and/or metastatic breast cancer. Documentation (from an immunohistochemistry (IHC) assays with a result of 3+ or fluorescence in situ hybridization or FISH assay with a positive result) 1 that the patient is human epidermal receptor type 2 (HER2) positive. The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 12 week duration; however if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR REAUTHORIZATION FOR BREAST CANCER: The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 12 week duration, however if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved, however if any of the above criteria is not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Breast Cancer: For use an adjuvant therapy for patient with HER2 over expressing, node-positive breast cancer when used in onjunction with doxorubicin and cyclophosphamide followed by paclitaxel and Herceptin treatment For use as monotherapy for patient with HER2 over expressing, metastatic breast cancer who have received one or more chemotherapy treatments for their metastatic disease For use as combination therapy with paclitaxel for patient with HER2 over expressing, metastatic breast cancer who has not received chemotherapy for their metastatic disease

DOSAGE AND ADMINISTRATION: Recommended dose for the initial infusion is 4 mg/kg administered as a 90 minute intravenous (IV) infusion. If the initial infusion was well tolerated, subsequent weekly doses of 2 mg/kg as a 30 minute infusion should be given. OR Recommended dose for the initial infusion is 8 mg/kg administered as a 90 minute intravenous (IV) infusion. If the initial infusion was well tolerated, subsequent doses of 6 mg/kg as a 90 minute infusion should be given. OR Recommended dose for the initial infusion is 4 mg/kg administered as a 90 minute intravenous (IV) infusion. If the initial infusion was well tolerated, subsequent weekly doses of 2 mg/kg as a 30 minute infusion for the next 11-17 weeks then followed by 6 mg/kg every 3 weeks. Herceptin should not be administered as an IV push or bolus. DOSING MODIFICATIONS: Due to cardiomyopathy: Left ventricular ejection fraction (LVEF) should be assessed prior to initiation of Herceptin treatment and also through out therapy. Dosing should be withheld for at least 4 weeks and repeat LVEF assessment every 4 weeks if there is a 16% or more absolute decrease in LVEF from the patient s pretreatment value or if the LVEF falls below the institutional lower limit of normal and there is a 10% or more absolute decrease in LVEF from the patient s pretreatment value. The Herceptin therapy may be restarted if, within 4 to 8 weeks, the patient s LVEF value returns to within normal limits and the absolute decrease from that patient s baseline is less then 15%. The permanent discontinuation of Herceptin should occur when there is a persistent (more than 8 weeks) decline in LVEF or there where 3 or more occasions of Herceptin dosing suspension due to cardiomyopathy 1 = Examples of immunohistochemistry (IHC) assays are HercepTest and Pathway and examples of fluorescence in situ hybridization (FISH) assays are PathVysion and HER2 FISH pharmdx. REFERENCES: 1. NCCN Clinical Practice Guidelines in Oncology : Breast Cancer; V.2.2007Update. 2. Herceptin Prescribing Information. Genentech Pharmaceutical, 6/2006 3. AHFS Drug Information 2007 4. Micromedex 2007 5. Hudis CA. Traztuzumab Mechanism of Action and Use in Clinical Practice. The New England Journal of Medicine 2007;357:39-51. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FOR HYALURONIC ACID DERIVATIVES EUFLEXXA (hyaluronate sodium): 20 mg/2ml syringe HYALGAN (hyaluronate sodium): 20mg/2ml syringe SYNVISC (hylan G-F 20): 16mg/2ml syringe SYNVISC One (hylan G-F 20): 48mg/6ml syringe SUPARTZ (hyaluronate sodium): 25mg/2.5ml syringe ORTHOVISC (hyaluronate sodium): 30mg/2ml syringe PA CRITERIA FOR INITIAL APPROVAL: A diagnosis of Osteoarthritis (OA)/Degenerative joint disease (DJD) of the knee There is documentation that the patient recently (over the past 4 months) has had adequate trials on simple analgesics (acetaminophen containing products) & NSAIDS (including 2 different prescription strength NSAIDS) on a continuous basis for 3 months without success or has a medical reason (intolerance, hypersensitivity, contraindication, etc) for not being able to utilize simple analgesic products and NSAIDS The patient has recently (within past 2 months) tried steroid injections and aspiration for effusion without success, per affected knee or has a medical reason for not being able to utilize steroid injections If the medication request is for Hyalgan, Synvisc, Supartz, Orthovisc or any other newly marketed hyaluronic acid derivative (HAD), the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Euflexxa to treat their medical condition. If all of the above conditions are met, the request will be approved for a 3 to 5-week duration (based the FDA labeled dose of the HAD requested); if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION: At least 6 months have elapsed since the previous course of HAD therapy for the treated knee(s). Documentation was submitted that the patient had an objective response to the treated knee(s) that lasted for > 6 months to previous HAD therapy, as documented by at least ONE of the following: Decreased joint pain or stiffness Improvement in standard indices such as WOMAC osteoarthritis index or Lequesne s functional index (See Glossary for definitions) Improved knee range of motion Decrease in midpatellar knee circumference in millimeters Synovial effusion absent or volume decreased Decrease in the need for intra-articular agents (anesthetics, corticosteroids), knee aspiration, analgesics or anti-inflammatory medications for the management of the treated knee(s) following the previous course of HAD that is consistent with pharmacy claims data. Documentation was submitted that the patient has a return of symptoms of osteoarthritis. If all of the above conditions are met, the request will be approved for a 3 to 5-week duration (based the FDA labeled dose of the HAD requested); if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Euflexxa, Hyalgan, Synvisc, Synvisc-One, Supartz and Orthovisc are all indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond to conservative non-pharmacologic therapy and simple analgesics. DOSAGE AND ADMINISTRATION: Euflexxa: Give a dose of 20 mg in 2 ml at weekly intervals for 3 weeks for a total of 3 injections. Hyalgan: Give a dose of 20 mg in 2 ml at weekly intervals for 5 weeks for a total of 5 injections. Synvisc: Give a dose of 16 mg in 2 ml at weekly intervals for 3 weeks for a total of 3 injections. Synvisc One: Given as one intra-articular injection. Supartz: Give a dose of 25 mg in 2.5 ml at weekly intervals for 5 weeks for a total of 5 injections.

Orthovisc: Give a dose of 30 mg in 2 ml at weekly intervals for 3 or 4 weeks for a total of 3 to 4 injections. **All hyaluronic acid derivatives are injected intra-articularly into the affected knee. Remove joint effusion if present before injecting any hyaluronic acid derivative. Injection of a local anesthetic (eg, lidocaine) subcutaneously prior to administration can be performed.** Glossary: Western Ontario and McMaster Universities Osteoarthritis index (WOMAC): is a disease specific, self-administered questionnaire developed to study patients with hip or knee OA. It consists of 24 questions, grouped into 3 subscales (pain, stiffness, and physical function). It measures clinically important patient relevant outcomes to drug therapy and fulfills criteria for validity, reliability, responsiveness and efficiency for use in research and OA clinical trials. Lequesne Functional Severity Index for the knee: is a disease-specific questionnaire which consists of 10 questions grouped into 3 subscales (pain or discomfort, activities of daily living and maximum distance walked). Total score ranges from 0-24, and higher scores indicate more severe handicap. REFERENCES: 1. Altman RD. Hochberg MC. Moskowitz RW. Et al Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee - American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis & Rheumatism. 2000; 43:1905-1915. 2. Kotz R, Kolarz G. Intra-articular Hyaluronic Acid: Duration of Effect and Results of Repeated Treatment Cycles. Amer Journ of Orthop. 1999; 28(11 Suppl): 5-7. 3. American Academy of Orthopaedic Surgeons. [resource of the World Wide Web]. www.aos.org. Accessed 2002 October 23. 4. Anonymous. Managing Osteoarthritis: New ACR Guidelines. Women s Health. 2001; 4:97-99. 5. Evanich, J. et al. Efficacy of Intraaticular Hyaluronic Acid injections in knee osteoarthritis. Clinical Othopaedics and related research. 2001; 390:173-181 6. Raynauld J-P et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee. A randomized, double-blind, placebo- controlled trial. Arthritis Rheum 2003 Feb;48:370-7 7. Leopold SS et al. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee: A prospective, randmized trial. J Bone Joint Surg Am 2003 Jul; 85:1197-203. 8. Hochberg MC. Altman RD. Brandt KD. Et al. American College of Rheumatology. Guidelines for the medical management of osteoarthritis. Arthritis & Rheumatism. 1995; 38(11):1541-1546. 9. American Academy of Orthopaedic Surgeons step approach to treating adult patients with osteoarthritis of the Knee.Phase I,II. Version 1.0. 2003. 10. Scali JJ. Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: a long term study. European journal of Rheumatology and Inflammation. 1995;15(1):1-6. 11. Kirchner M. Marshall K. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. OsteoArthritis and Cartilage.2005;1-9. 12. Hanson EC. Sodium hyaluronate-application in a community practice. A supplement to the American Journal of Orthopedics.November 1999.pp11-12. 13. Felson DT. Anderson JJ. Hyaluronate sodium injections for osteoarthritis: hope, hype and hard truths. Archives of Internal Medicine. 2002;162(3):245-247. 14. Brandt KD. Block JA. Michalski JP. Et al. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. Clinical Orthopaedics and Related Research. 2001;1(385):130-143. 15. Petrella RJ. DiSelvestro MD. Hildebrand C. Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Archives of Internal Medicine. 2002;162(3):292-298. 16. Day R. Brooks P. Conaghan PG. Et al. A double-blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee. The Journal of Rheumatology.2004;31:775-782. 17. Niethard FU. Pathogenesis of osteoarthritis Approaches to specific therapy. A supplement to the American Journal of Orthopedics. November 1999.pp8-10. 18. Medical Policy Synvisc, Supartz, Hyalgan: Blue Cross California 19. Aetna Coverage Policy Bulletins. Subject Sodium hyaluronate and Hylan G-F20.4/26/02 20. Schwenk TL. Journal Watch. Hyaluronic acid is minimally effective in osteoarthritis. 1/23/04. 21. Brett AS. Journal Watch. Intra-articulr hyaluronic acid vs. steroids for knee osteoarthritis. 7/29/03.

22. Rapp SM. Hyaluronic acid meta-analysis results, methodology questioned. Orthopedics Today. 2004. 23. Brett AS. Journal Watch. Repeated steroid injections for knee osteoarthritis: beneficial or harmful? 3/21/03. 24. Euflexxa product information. 2/06. 25. Hyalgan product information. 1/09. 26. Orthovisc product information 6/05. 27. Synvisc product information 12/06. 28. Synvisc One product information 3/09 29. Supartz product information 1/2007 Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Infergen (interferon alfacon-1): 15 mcg/0.5 ml vial, 9 mcg/0.3 ml vial Ribavirin: 200mg tablet Section A: PA Criteria for authorization of combination treatment with Infergen and ribavirin in patients who have failed treatment with either a pegylated interferon or standard interferon with or without ribavirin. The appropriate lab-work was provided with request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype, if liver function studies are within normal limits before starting therapy a liver biopsy report was submitted. The patient s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1- see table 3) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The patient does not have a history of kidney, heart, or other solid-organ transplant (excluding liver transplant). The patient has a documented trial and failure (non-responder or relapsed) of at least two of the listed therapeutic options, with or without Ribavirin, OR has a documented medical reason for not being able to tolerate any of the listed therapeutic options. The therapeutic options include: pegylated interferons (Peg Intron or Pegasys ) or non-pegylated interferon (Intron A ). The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing. If all of the above conditions are met, and the patient has Genotype 1, 4 or 6 or the patient has Genotype 2 or 3 and is co-infected with HIV, the request will be approved with 16-week duration; if the patient has Genotype 2 or 3 and not co-infected with HIV, the request will be approved for the 24 weeks of therapy, if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Section B: PA Criteria for authorization of monotherapy with Infergen for patients who failed previous treatment with pegylated interferon or standard interferon The patient has a documented trial and failure (non-responder or relapsed) of at least two of the listed therapeutic options as monotherapy OR has a documented medical reason for not being able to tolerate any of the listed therapeutic options. The therapeutic options include: pegylated interferons (Peg Intron or Pegasys ) or non-pegylated interferon (Intron A ). The patient has a documented medical reason (i.e. ESRD, etc.) for not receiving Ribavirin. The appropriate lab-work was provided with request including HCV RNA viral load (result within one month of starting therapy), liver function studies (result within one month of starting therapy) and genotype, if liver function studies are within normal limits before starting therapy a liver biopsy report was submitted. The patient s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are abnormal or the patient has a liver biopsy result (greater than Ishak stage 0-2 or Metavir, IASL, and Batts-Ludwig stage 0-1- see table 3) or another noninvasive procedure that shows the patients has advanced to severe fibrosis. The provider submitted documentation that the patients had clinical signs or symptoms or extra-hepatic (cryoglobulinemia, glomerulonephritis see table 2) symptoms that improved while on interferon therapy or worsened while off therapy despite not eradicating the Hepatitis C virus. The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated

If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing. If all of the above conditions are met, and the patient has Genotype 1, 4 or 6 or the patient has Genotype 2 or 3 and is co-infected with HIV, the request will be approved with 16-week duration; if the patient has Genotype 2 or 3 and not co-infected with HIV, the request will be approved for the 24 weeks of therapy, if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Section C: PA Criteria for re-authorization for patients who received treatment for 12-16 weeks of therapy Appropriate lab work was forwarded with request (repeat HCV load, liver function test including ALT/AST) dated 12 weeks after starting therapy to evaluate initial response to medication. The patient has responded to treatment (complete eradication of HCV RNA levels or > 2 log decrease in HCV RNA viral load after receiving 12-16 weeks of therapy) and the dose that has been prescribed for the patient is consistent with the FDA dosing recommendations listed below. The patient does not have a medical condition or other risk factors (see table 1) in which treatment is contraindicated If the patient has a history of a co-morbid condition that could be a contraindication, the prescribing physician submitted adequate documentation that indicates the condition is either clinically resolved or is being appropriately medically managed and stable. The dose that has been prescribed for the patient is consistent with the FDA recommended dosing. If all of the above conditions are met, the request will be approved for up to a 48-week total duration for Genotypes 1 and other genotypes except for 2 and 3, if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Unstable angina or severe cardiac disease (CABG, MI, Arrhythmias) in past 12 months. Severe COPD Uncontrolled autoimmune disorder Pregnancy Non-compliance Inability to self-inject medications Table 1. Contraindications to Hepatitis-C Therapy Severe uncontrolled Psychiatric disease, especially depression with current suicidal risk IVDA Alcohol abuse Inability to use birth control Contraindications to Infergen Hepatic decompensation (Child-Pugh score > 6 [class B and C]) Autoimmune hepatitis Known hypersensitivity reactiosn such as uticaria, angioedema, bronchoconstriction, anaphylaxis to interferon alphas or to any component of the product Contraindications to ribavirin Women who are pregnant Men whose female partners are pregnant Patients with hemoglobinopathies (e.g., thaslassemia major, sickle-cell anemia) Patients with hypersensitivity to ribavirin or any other component of the product Patients with creatinine clearance <50mL/min Coadministration with didanosine Table 2. Extra-hepatic Signs Symptoms associated with hepatitis C infection Glomerulonephritis * Joint and muscle aches Porphyria cutanea tarda * Skin rash * Kidney disease Thrombocytopenic purpura

* Neuropath Cryoglobulinemia (1-2% of Lichen planus patients Mooren's corneal ulcer Sjögren's syndrome Polyarteritis nodosa Cutaneous Vasculitis Autoantibody formation * Cryoglobulins, Rheumatoid factor, and low complement levels * Associated with cryoglobulinemia Table 3. Comparison of Scoring System for a Liver Biopsy (Histological Stage) Stage IASL Batts-Ludwig Metavir Ishak 0 No Fibrosis No Fibrosis No Fibrosis No Fibrosis 1 Mild Fibrosis Fibrous portal expansion 2 Moderate Fibrosis Rate bridges or septae 3 Severe Fibrosis Numerous bridges or septae Periportal portal expansion Periportal septae 1 Porto-central septae Fibrous expansion of some portal areas with or without short fibrous septa Fibrous expansion of most portal areas with or without short fibrous septa Fibrous expansion of most portal areas with occasional portal to portal bridging 4 Cirrhosis Cirrhosis Cirrhosis Fibrous expansion of most portal areas with marked bridging 5 Marked bridging with occasional nodules 6 Cirrhosis IASL = International Association for the Study of the liver FDA INDICATION: Infergen is indicated for the treatment of chronic hepatitis C viral (HVC) infection in patients 18 years of age or older with compensated liver disease. The following points should be considered when initiating treatment with Infergen: o Use of monotherapy with an interferon such as Infergen for the treatment of hepatitis C is not recommended unless a patient is unable to take ribavirin. o The safety and efficacy of the combination of Infergen/ribavirin in treatment-naïve patients or in patients coinfected with HBV or HIV-1 have not been evaluated o Patients with the following any or a combination of the following characteristics are less likely to benefit from retreatment with combination therapy o Response of <1 log 10 drop HCV RNA on previous treatment o Genotype 1 o High viral load (> 850,000 IU/ml) o African-American race o Presence of cirrhosis o No safety and efficacy data are available for treatment of longer than one year Table 4. Dosing of Ribavirin when combined with Infergen Ribavirin combination therapy Genotypes Body weight (kg) Amount of Ribavirin (mg) to administer Genotype 1, 4 BW < 75 kg 1000 mg/day for 48 weeks Genotype 1, 4 BW > 75 kg 1200 mg/day for 48 weeks

Genotype 2, 3 All 800 mg/day for 24 weeks DOSAGE AND ADMINISTRATION: The FDA recommended dosing of Infergen: o As Monotherapy: For the treatment of chronic HCV infection the dose is 9 mcg three times a week (TIW) administered as a SC single injection for 24 weeks. Patients who tolerated previous interferon therapy and did not respond or relapsed following its discontinuation may be subsequently treated with 15 mcg of Infergen TIW administered as a SC single injection for up to 48 weeks. o As Combination Therapy: The recommended dose is 15 mcg daily administered as a single SQ injection in combination with weight-based ribavirin at 1,000mg-1,200mg (<75kg and >75kg) orally in two divided doses for up to 48 weeks. DOSE REDUCTION: For patients who experience a severe adverse reaction during treatment the Infergen and/or ribavirin should be discontinued or the dose modified until the adverse event ends or decreases in severity. If persistent or recurrent serious adverse events develop despite adequate dosage adjustments then treatment must be discontinued. Dose Modifications on Monotherapy: Dose reduction to 7.5 mcg may be necessary following a serious adverse reaction Dose Modifications on Infergen/Ribavirin Combination: Therapy: A stepwise dose reduction from 15 mcg to 9mcg and from 9 mcg to 6 mcg may be necessary for serious adverse reactions. REFERENCES: 1. Centers for Disease Control and Prevention, Workowski KA. Berman SM. Hepatitis C. Sexually transmitted diseases treatment guidelines 2006. 2010. MMR Morbidity Mortality Weekly Report.2010 Dec 17;59(RR12):1-110. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm. Accessed 01/07/14. 2. Yee H, Chang M, Pocha C. et al. Update on the Management and Treatment of Hepatitis C Virus Infection: Recommendations from the Department of Verterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Am J Gastroenterol. 2012 May; 107(5): 669-89; quiz 690 doi: 10.1038/ajg.2012.48. 3. Ghany MG, Strader DB, Thomas DL, Seef LB. Diagnosis, management and treatment of Hepatitis C: An Update. American Association for the Study of Liver Diseases Practice Guideline. Hepatology. 2008; 49(4): 1335-74. 4. Centers of Excellence in Hepatitis C Research and Education,http://www.hepatitis.va.gov (June 20, 2003) 5. National Digestive Diseases Information Clearinghouse. A service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Chronic Hepatitis C: Current Disease Management. Available from www.niddk.nih.gov (February 2003) 6. NIH Consensus Development Program. Management of Hepatitis C:2002. Available from URL: http://consensus.nig.gov/2002/2002hepatitisc2002116html.htm 7. Fattovich G. Zagni I. Minola E. et al. A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C. Journal of Hepatology. 2003;39:843-849. 8. Infergen Prescribing Information. Kadmon Pharmaceuticals, LLC. 7/2013 9. Copegus Prescribing Information. Genentech, Inc. 2/2013 10. Bacon BR, Shiffman ML, Mendes F, et al. Retreating Chronic Hepatitis C with Daily Interferon Alfacon-1/Ribavirin After Nonresponse to Pegylated Interferon/Ribavirin: DIRECT Results. Hepatology 2009; 49. Revision/Review Date: 01/2014 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE BISPHOSPHONATES & SKELETAL- RELATED EVENTS MEDICATIONS Preferred Agent Pamidronate disodium (Aredia ): 3mg/ml, 6 mg/ml, 9 mg/ml liquid in10 ml vials, 30 mg, 90 mg vials Non-preferred Agents (requires prior authorization) Zoledronic Acid (Zometa ): 4 mg/5 ml vial Denosumab (Xgeva ): 120mg/1.7ml PREFERRED STATUS: Generic Pamidronate Preferred Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), Drug Package Insert) as defined in the Social Security Act 1927 or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), or the National Institutes of Health (NIH) Consensus Panel standard of care guidelines. If the medication request is for Denosumab (Xgeva), Zolederonic Acid (Zometa), or any other brand only available injectable bisphosphonate or agent indicated for the prevention or treatment of skeletal-related events in patients with bone metastases for treating a medical condition other than postmenopausal osteoporosis, the patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial (including dates, 3 months or more of therapy) of generic Pamidronate (Aredia) or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing these agents to manage their medical condition. If the medication request if for denosumab (Xgeva) for treating Giant Cell Tumor of Bone, the patient has documentation submitted that the giant cell tumor of bone is unresectable or that surgical resection is likely to result in severe morbidity. Prescribed dosing of medication is within FDA approved indications or is supported by the medical compendium as defined by the Social Security Act or per the NCCN, ASCO, or NIH standard of care guidelines. If all of the above conditions are met, the request will be approved for 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, NOF or NIH standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN, ASCO, or NIH standard of care guidelines. Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN, ASCO, or NIH standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN, ASCO, or NIH standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA APPROVED INDICATIONS AND DOSING:

Pamidronate disodium (Aredia): Hypercalcemia of Malignancy in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. o For patients with moderate hypercalcemia (corrected serum calcium of approximately 12-13.5 mg/dl) the recommended dose is 60 to 90 mg given as a single dose, intravenous infusion over 2 24 hours. Longer infusions (i.e. > 2hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency. o For patients with severe hypercalcemia (corrected serum calcium >13.5 mg/dl) the recommended dose is 90 mg given as a single dose intravenous infusion over 2 24 hours. Longer infusions (i.e. > 2hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency. o A limited number of patients have received more than one treatment for hypercalcemia. Retreatment with Aredia, in patients who show complete or partial response initially, may be carried out if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. The dose and manner of retreatment is identical to that of the initial treatment. Paget s Disease is indicated for the treatment of patients with moderate to severe Paget s disease of bone. The effectiveness of Aredia was demonstrated primarily in patients with serum alkaline phosphatase > 3 times the upper limit of normal. o The recommended dose is 30 mg daily, administered as a 4 hour infusion on 3 consecutive days for a total dose of 90mg. A limited number of patients have received more than one treatment in clinical trials. When clinically indicated, patients should be retreated at the dose of initial therapy. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma in conjunction with standard antineoplastic therapy is indicated for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. o The recommended dose for patients with osteolytic bone lesions of multiple myeloma is 90 mg administered as a 4 hour infusion given on a monthly basis. Limited information is available on the use of Aredia in patients with a serum creatinine > 3.0g/dL. o The recommended dose for patients with osteolytic bone metastases of breast cancer is 90 mg administered over a 2 hour infusion given every 3-4 weeks. Denosumab (Xgeva): Bone Metastasis from Solid Tumors is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors o The recommended dose is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Giant Cell Tumor of Bone is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity o The recommended dose is 120mg administered every 4 weeks with additional 120mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia Zoledronic Acid (Zometa):

Hypercalcemia of Malignancy is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cca) of >12 mg/dl [3.0 mmol/l] using the formula: cca in mg/dl = Ca in mg/dl + 0.8 (mid-range of measure albumin in mg/dl). o The maximum recommended dose is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive Zometa should have their serum creatinine assessed prior to each treatment. Dose adjustments are not necessary in treating patients with hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine < 4.5mg/dL). Multiple Myeloma and Bone Metastases of Solid Tumor is indicated for the treatment of patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. o The recommended dose for patients with a CrCl > 60 ml/min is 4 mg infused over no less than 15 minutes every 3-4 weeks. The optimal duration of therapy is not known. Patients should also be administered an oral calcium supplement of 500mg and a multiple vitamin containing 400 IU of vitamin D daily. Upon initiation of treatment the recommended dose for patients with reduced renal function should be: Reduced Doses for Patients with a Baseline CrCl < 60ml/min Baseline Creatinine Clearance (ml/min) Recommended Dose of Zometa > 60 4 mg 50 60 3.5 mg 40 49 3.3 mg 30 39 3 mg Definition of Hypercalcemia Normal serum calcium (Ca) level is 8-10 mg/dl (2-2.5 mmol/l) Mild: Total Ca 10.5-11.9 mg/dl (2.5-3mmol/L) Moderate: Total Ca 12-13.9 mg/dl (3-3.5 mmol/l) Hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dl (>2.5 mmol/l) Hypercalcemic crisis: Total Ca 14-16 mg/dl (3.5-4 mmol/l) For every 1 g/dl (1 g/l) drop in serum albumin below 4 g/dl (40 g/l), measured serum calcium decreases by 0.8 mg/dl (0.02 mmol/l). Therefore, if albumin level < 4 g/dl (40 g/l) need to correct calcium based on the following formulas: Corrected Ca = (4g/dL - (plasma albumin) X 0.8 + serum calcium, g/dl) or Corrected Ca = serum calcium, mmol/l = {(40-[plasma albumin]) X 0.02} References: 1. Murphy KC. Nakashima L. Khoo K. BCCA Protocol Summary Guidelines for the diagnosis and management of malignancy related hypercalcemia. BC Cancer Agency: Care and Research web site: http://www.bccancer.bc.ca. Accessed on March 2, 2005 2. Novartis Pharmaceutical Corporation. Zometa (zoledronic acid) injection prescribing information. Updated 11/2012. 3. Novartis Pharmaceutical Corporatin. Aredia(pamidronate disodium) injection prescribing information. Updated 05/2012. 4. Xgeva Prescribing Information. Amgen 6/2013. 5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Breast Cancer. Prostate Cancer. Multiple Myeloma Available at http://www.nccn.org/patients/patient_gls/_englis/_prostate/4_treatment.asp 6. Berenson, JR, Hillner BE, Kyle RA, et al. American society of clinical oncology clinical practice guidelines: the role of bisphosphonate in multiple myeloma. J Clin Oncol 2002; 20(17): 3719-36.

7. Coleman RE. Efficacy of zoledronic acid and pamidronate in breast cancer patients: a comparative analysis of randomized phase III trials. Am J of Clin Oncol 2002; 25(suppl 1): S25-S31. 8. Widler L, Jaeggi KA, Glatt M et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J of Med Chem 2002; 45(17): 3721-38 (Abstract). 9. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003; 98:1735-44. 10. Rosen LS, Gordon DH, Dugan W Jr, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004; 100:36-43. 11. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19(2): 558-67. 12. Clinical Policy Bulletins. Pamidronate (Aredia). http://www.aetna.com/cpb/data/cpba0672.html. Accessed on March 14, 2005. 13. Magnuson WG. Daniels CE. Calis KA. Et al. National Institute of Health. Pharmacy Update. Zoledronic Acid for Injection. Special Issue. March/April 2002. 14. Kellinsalmi M. Monkkonen H. Monkkonen J. et al. In vitro comparison of Clodronate, Pamidronate and Zoledronic Acid effects on rate osteoclasts and human stem cell-derived osteoblasts. Basic & Clinical Pharmacology & Toxicology. 2005;97:382-391. 15. Brown JE. Neville-Webbe H. Coleman RE. The role of bisphosphonates in breast and prostate cancers. Endocrine-Related Cancer. 2004;11: 207-224. 16. Reed SD. Radeva JI. Glendenning A. et al. Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma. American Journal of Clinical Oncology. 2005;28 (1):8-16. 17. Parker, CC. The role of bisphosphonates in the treatment of prostate cancer. BJU International.2005;95:935-938. 18. Coldwell, B. Head LR. White D. et al. Guidelines for the use of zoledronic acid for the treatment of tumor-induced hypercalcemia QEII health sciences centre/cancer care Nova Scotia. Oncology Subcommittee. 2001 19. Oneschuk D. et al. Palliative.org Regional palliative care program in Edmonton Alberta. Clinical Information on Hypercalcemia of Malignancy. http://www.palliative.org/pc/clinicalinfo/pcaretips/hypercalcemia.html. Accessed 3/16/05. 20. Hillner BE. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonate Expert Panel. Journal of Clinical Oncology. 2000;18 (6):1378-91. Abstract 21. Hillner BE. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. Journal of Clinical Oncology.2003;21 (21):4042-57. Abstract. 22. CancerConsultants.com Treatment for Cancer-Related Bone Complications. Last updated 1/2005. 23. Weaver CH. Et al. CancerConsultants.com. Bone Complications and Cancer. Last updated 1/2005. 24. Coleman RE. Bisphosphonates: Clinical Experience. The Oncologist. 2004;9(suppl 4):14-27. 25. Berensen JR. Recommendations for zoledronic acid treatment of patients with bone metastases. Symptom management and supportive care. The Oncologist. 2005;10:52-62. 26. http://www.oncolink.upenn.edu/resources/article.cfm?c. Zoledronic acid better than pamidronate for bone metastatses from breast cancer. 1/15/04. 27. Markowitz GS. Fine PL. Stack JI. Et al. Toxic acute tubular necrosis following treatment with zoledronate. International Society of Nephrology. 2003;64 (1):281-289. 28. Lipton A. Small E. Saad F. et al. The new bisphosphonate, Zometa, decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Investigation. 2002; 20(suppl 2):45-54. Abstract. 29. McCormack PL. Plosker GL. Ibandronic acid. A review of its use in the treatment of metastases of breast cancer. Drugs. 2006;66 (5):711-728. 30. Body JJ. Diel IJ. Lichinitser MR. Et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Annals of Oncology. 2003;14:1399-1405. 31. Diel IJ. Body JJ. Lichinitser MR. Et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. European Journal of Cancer. 2005;40:1704-1712. 32. NIH Consensus Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285(6): 785-95 33. Dawson-Hughes B. Gold DT. Rodbard HW. Et al. Physician s Guide to Prevention and treatment of osteoporosis. Developed by the National Osteoporosis Foundation in collaboration with American Academy of Orthopaedic Surgeons, American Academy of Physical Medicine and Rehabilitation, American College of Obstetricians and Gynecologists, American College of Radiology, American College of Rheumatology, American Geriatrics Society, American Medical Association, International Society for Physical Medicine and Rehabilitation and The Endocrine Society. Updated 9/05. 34. Small EJ. Smith MR. Seaman JJ et al. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. Journal of Clinical Oncology. 2003; 21 (23):4277-4284. 35. Saad F. Gleason DM. Murray R. et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. Journal of the National Cancer Institute.2002; 94(19):1458-1468. 36. Kelly WK. Steineck G. Editorial. Bisphosphonates for men with prostate cancer: sifting through the rubble. Journal of Clinical Oncology. 2003; 21(23):4261-4262. 37. Ruggerio S. Gralow J. Marx RE. Et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. Journal of Oncology Practice. 2006;2(1):7-14. 38. US Department of Health and Human Services. National Institutes of Health. Oral Complications of Cancer Treatment: What the oral health team can do. Publication No. 02-4372. 6/02. Revision/Review Date: 06/2013 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE BISPHOSPHONATES Preferred Agent (requires prior authorization) Pamidronate disodium (Aredia ): 3mg/ml, 6 mg/ml, 9 mg/ml liquid in10 ml vials, 30 mg, 90 mg vials Non-preferred Agents (requires prior authorization) Zoledronic Acid (Zometa ): 4 mg/5 ml vial Ibandronate sodium (Boniva Injection): 3 mg/ml single-use Denosumab (Xgeva ): 120mg/1.7ml Initial Approval: The request for the medication is for an Food and Drug Administration (FDA) approved indication, or is used for a medical condition that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), DrugPoints, Drug Package Insert) as defined in the Social Security Act 1927 or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), National Osteoporosis Foundation (NOF), or the National Institutes of Health (NIH) Consensus Panel standard of care guidelines. If the medication request is for Zoledronic Acid (Zometa ), Denosumab (Xgeva ) or Ibandronate (Boniva Injection) or any other brand only available injectable bisphosphonate for treating a medical condition other than postmenopausal osteoporosis or bone metastasis in prostate cancer, the patient has a documented (consistent with pharmacy claims data) treatment failure (See Definition of End Points for additional information) after receiving an adequate trial (including dates, 3 months or more of therapy) of generic Pamidronate (Aredia ) or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing generic Pamidronate (Aredia ) to manage their medical condition. FOR ANY REQUEST FOR BONIVA INJECTION FOR THE TREATMENT OF OSTEOPOROSIS PLEASE REFER TO THE SEPARATE BONIVA INJECTION PROTOCOL. Prescribed dosing of medication is within FDA approved indications or is supported by the medical compendium as defined by the Social Security Act or per the NCCN, ASCO, NOF or NIH standard of care guidelines. If all of the above conditions are met, the request will be approved for 3 months or as recommended per FDA approved indications or as defined by the medical compendium as defined above or per the NCCN, ASCO, NOF or NIH standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Reauthorization of Medication: The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, or per recommendations of the medical compendium as described above, or per the NCCN, ASCO, NOF or NIH standard of care guidelines. Prescribed dosing of medication is within FDA approved indications or supported by the medical compendium as defined by the Social Security Act or per the NCCN, ASCO, NOF or NIH standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 3 months or as recommended per FDA approved indications or as defined by the medical compendium as defined above or per the NCCN, ASCO, NOF or NIH standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review FDA APPROVED INDICATIONS AND DOSING: Pamidronate disodium (Aredia ): Hypercalcemia of Malignancy in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. o o For patients with moderate hypercalcemia (corrected serum calcium of approximately 12-13.5 mg/dl) the recommended dose is 60 to 90 mg given as a single dose, intravenous infusion over 2 24 hours. For patients with severe hypercalcemia (corrected serum calcium >13.5 mg/dl) the recommended dose is 90 mg given as a single dose intravenous infusion over 2 24 hours. Longer infusions (i.e. > 2hours) may reduce the risk for renal toxicity, particularly in patients with preexisting renal insufficiency.

o A limited number of patients have received more than one treatment for hypercalcemia. Retreatment with Aredia, in patients who show complete or partial response initially, may be carried out if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. The dose and manner of retreatment is identical to that of the initial treatment. Paget s Disease is indicated for the treatment of patients with moderate to severe Paget s disease of bone. The effectiveness of Aredia was demonstrated primarily in patients with serum alkaline phosphatase > 3 times the upper limit of normal. o The recommended dose is 30 mg daily, administered as a 4 hour infusion on 3 consecutive days for a total dose of 90mg. A limited number of patients have received more than one treatment in clinical trials. When clinically indicated, patients should be retreated at the dose of initial therapy. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma in conjunction with standard antineoplastic therapy is indicated for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. o o The recommended dose for patients with osteolytic bone lesions of multiple myeloma is 90 mg administered as a 4 hour infusion given on a monthly basis. Limited information is available on the use of Aredia in patients with a serum creatinine > 3.0g/dL. The recommended dose for patients with osteolytic bone metastases of bone cancer is 90 mg administered over a 2 hour infusion given every 3-4 weeks. Zoledronic Acid (Zometa ): Hypercalcemia of Malignancy is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cca) of >12 mg/dl {3.0 mmol/l] using the formula: cca in mg/dl = Ca in mg/dl + 0.8 (mid-rang of measure albumin in mg/dl). o The maximum recommended dose is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients who receive Zometa should have their serum creatinine assessed prior to each treatment. Dose adjustments are not necessary in treating patients with hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine < 4.5mg/dL). Multiple Myeloma and Bone Metastases of Solid Tumor is indicated for the treatment of patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. o The recommended dose for patients with a CrCl > 60 ml/min is 4 mg infused over no less than 15 minutes every 3-4 weeks. The optimal duration of therapy is not known. Patients should also be administered an oral calcium supplement of 500mg and a multiple vitamin containing 400 IU of vitamin D daily. Upon initiation of treatment the recommended dose for patients with reduced renal function should be: Reduced Doses for Patients with a Baseline CrCl < 60ml/min Baseline Creatinine Clearance (ml/min) Recommended Dose of Zometa > 60 4 mg 50 60 3.5 mg 40 49 3.3 mg 30 39 3 mg

Ibandronate sodium (Boniva Injection): Osteoporosis is indicated for the treatment of osteoporosis in postmenopausal women. o The recommended dose is 3 mg every 3 months administered intravenously over a 15 to 30 second period. Denosumab (Xgeva ): Bone Metasasis from Solid Tumors indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. o The recommended dose is 120 mg administered as a subcutanous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Glossary: Definition of End Points: Intermediate outcomes in metastatic bone disease include biomarkers, radiographic criteria for bony response or progression, and in the adjuvant setting, bone mineral density. Non-fatal skeletal-related complications can be measured as meaningful endpoints to treatment such fractures, spinal cord compression, hypercalcemia and pain. A change in frequency of these events should be combined to demonstrate an improvement in quality of life. Skeletal related events (SREs) divided by the time on drug therapy can be used as a composite end point. Examples of SREs are pathologic fracture, spinal cord collapse/compression, or requiring surgery or therapeutic radiation therapy for bone pain or bone-related cause. Time to first SRE after starting drug therapy is a reliable endpoint. Clinical endpoints for osteoporosis include bone mineral density score, x-ray, fracture history, height loss, markers of bone formation or pain score. No evidence of improved or stable bone mineral density detected by X-ray or densitometry after 12 months of drug therapy or an osteoporotic fracture, height loss or kyphosis [indicative of vertebral (spinal fracture)] after 6 months or more of drug therapy can be considered treatment failure. Definition of Hypercalcemia Normal serum calcium (Ca) level is 8-10 mg/dl (2-2.5 mmol/l) Mild: Total Ca 10.5-11.9 mg/dl (2.5-3mmol/L) Moderate: Total Ca 12-13.9 mg/dl (3-3.5 mmol/l) Hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dl (>2.5 mmol/l) Hypercalcemic crisis: Total Ca 14-16 mg/dl (3.5-4 mmol/l) For every 1 g/dl (1 g/l) drop in serum albumin below 4 g/dl (40 g/l), measured serum calcium decreases by 0.8 mg/dl (0.02 mmol/l). Therefore, if albumin level < 4 g/dl (40 g/l) need to correct calcium based on the following formulas: Corrected Ca = (4g/dL - (plasma albumin) X 0.8 + serum calcium, g/dl) or Corrected Ca = serum calcium, mmol/l = {(40-[plasma albumin]) X 0.02} Osteonecrosis of the Jaw (ONJ): may remain asymptomatic for many weeks or months and is typically identified by exposed bone in the oral cavity upon clinical presentation. The lesions become symptomatic when infection or trauma is involved at the site or surrounding areas. Signs and symptoms include localized pain; soft-tissue swelling and inflammation, loosening of previously stable teeth, drainage and exposed bone. These symptoms most commonly occur at the site of previous tooth extraction or dental-surgical interventions. References: 39. Murphy KC. Nakashima L. Khoo K. BCCA Protocol Summary Guidelines for the diagnosis and management of malignancy related hypercalcemia. BC Cancer Agency: Care and Research web site. Revised May 1,2009. 40. Novartis Pharmaceutical Corporation. Zometa (zoledronic acid) injection prescribing information. Updated 3/2008. 41. Novartis Pharmaceutical Corporation. Aredia (pamidronate disodium) injection prescribing information. Updated 11/2008 42. Boniva Injection Prescribing Information. Roche Pharmaceuticals,July 2009 43. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Breast Cancer. Prostate Cancer. Multiple Myeloma Accessed October 2009. Available at http://www.nccn.org.

44. Berenson, JR, Hillner BE, Kyle RA, et al. American society of clinical oncology clinical practice guidelines: the role of bisphosphonate in multiple myeloma. J Clin Oncol 2002; 20(17): 3719-36. 45. Coleman RE. Efficacy of zoledronic acid and pamidronate in breast cancer patients: a comparative analysis of randomized phase III trials. Am J of Clin Oncol 2002; 25(suppl 1): S25-S31. 46. Widler L, Jaeggi KA, Glatt M et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J of Med Chem 2002; 45(17): 3721-38 (Abstract). 47. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003; 98:1735-44. 48. Rosen LS, Gordon DH, Dugan W Jr, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004; 100:36-43. 49. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19(2): 558-67. 50. Magnuson WG. Daniels CE. Calis KA. Et al. National Institute of Health. Pharmacy Update. Zoledronic Acid for Injection. Special Issue. March/April 2002. 51. Kellinsalmi M. Monkkonen H. Monkkonen J. et al. In vitro comparison of Clodronate, Pamidronate and Zoledronic Acid effects on rate osteoclasts and human stem cell-derived osteoblasts. Basic & Clinical Pharmacology & Toxicology. 2005;97:382-391. 52. Brown JE. Neville-Webbe H. Coleman RE. The role of bisphosphonates in breast and prostate cancers. Endocrine-Related Cancer. 2004;11: 207-224. 53. Reed SD. Radeva JI. Glendenning A. et al. Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma. American Journal of Clinical Oncology. 2005;28 (1):8-16. 54. Parker, CC. The role of bisphosphonates in the treatment of prostate cancer. BJU International.2005;95:935-938. 55. Coldwell, B. Head LR. White D. et al. Guidelines for the use of zoledronic acid for the treatment of tumor-induced hypercalcemia QEII health sciences centre/cancer care Nova Scotia. Oncology Subcommittee. 2001 56. Oneschuk D. et al. Palliative.org Regional palliative care program in Edmonton Alberta. Clinical Information on Hypercalcemia of Malignancy. http://www.palliative.org/pc/clinicalinfo/pcaretips/hypercalcemia.html. Accessed 3/16/05. 57. Hillner BE. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonate Expert Panel. Journal of Clinical Oncology. 2000;18 (6):1378-91. Abstract 58. Hillner BE. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. Journal of Clinical Oncology.2003;21 (21):4042-57. Abstract. 59. CancerConsultants.com Treatment for Cancer-Related Bone Complications. Last updated 1/2005. 60. Weaver CH. Et al. CancerConsultants.com. Bone Complications and Cancer. Last updated 1/2005. 61. Coleman RE. Bisphosphonates: Clinical Experience. The Oncologist. 2004;9(suppl 4):14-27. 62. Berensen JR. Recommendations for zoledronic acid treatment of patients with bone metastases. Symptom management and supportive care. The Oncologist. 2005;10:52-62. 63. http://www.oncolink.upenn.edu/resources/article.cfm?c. Zoledronic acid better than pamidronate for bone metastatses from breast cancer. 1/15/04. 64. Markowitz GS. Fine PL. Stack JI. Et al. Toxic acute tubular necrosis following treatment with zoledronate. International Society of Nephrology. 2003;64 (1):281-289. 65. Lipton A. Small E. Saad F. et al. The new bisphosphonate, Zometa, decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Investigation. 2002; 20(suppl 2):45-54. Abstract. 66. McCormack PL. Plosker GL. Ibandronic acid. A review of its use in the treatment of metastases of breast cancer. Drugs. 2006;66 (5):711-728. 67. Body JJ. Diel IJ. Lichinitser MR. Et al. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Annals of Oncology. 2003;14:1399-1405. 68. Diel IJ. Body JJ. Lichinitser MR. Et al. Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. European Journal of Cancer. 2005;40:1704-1712. 69. NIH Consensus Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285(6): 785-95 70. Dawson-Hughes B. Gold DT. Rodbard HW. Et al. Physician s Guide to Prevention and treatment of osteoporosis. Developed by the National Osteoporosis Foundation in collaboration with American Academy of Orthopaedic Surgeons, American Academy of Physical Medicine and Rehabilitation, American College of Obstetricians and Gynecologists, American College of Radiology, American College of Rheumatology, American Geriatrics Society, American Medical Association, International Society for Physical Medicine and Rehabilitation and The Endocrine Society. Updated 9/05. 71. Small EJ. Smith MR. Seaman JJ et al. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. Journal of Clinical Oncology. 2003; 21 (23):4277-4284.

72. Saad F. Gleason DM. Murray R. et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. Journal of the National Cancer Institute.2002; 94(19):1458-1468. 73. Kelly WK. Steineck G. Editorial. Bisphosphonates for men with prostate cancer: sifting through the rubble. Journal of Clinical Oncology. 2003; 21(23):4261-4262. Revision/Review Date: 11/2010 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA INTRANASAL CORTICOSTEROIDS FORMULARY STATUS: Formulary, Pays at Point-of-Sale FLONASE (fluticasone propionate) Nasal Suspension: 50mcg NASONEX (mometasone) Nasal Suspension: 50mcg (Children < 4 years of age) FORMULARY STATUS: Non-Formulary, Requires Prior Authorization BECONASE AQ (beclomethasone) Nasal Suspension: 42mcg NASONEX (mometasone) Nasal Suspension: 50mcg (Members > 4 years of age) NASACORT AQ (triamcinolone) Nasal Solution: 55mcg NASAREL (flunisolide) Nasal Solution: 25mcg, 29mcg OMNARIS (ciclesonide) Nasal Suspension: 50mcg RHINOCORT AQUA (budesonide) Nasal Suspension: 32mcg VERAMYST (fluticasone furoate) Nasal Suspension: 27.5mcg NOTE: Patient must meet criteria #1 for approval of the PA request. PA CRITERIA FOR APPROVAL: 1. Documented trial and failure or intolerance to Flonase for at least 4 weeks (28 days) of therapy. If the above condition is met, the request will be approved with a 12 month duration; if the above condition is not met, the request will be referred to a Medical Director for medical necessity review. REFERENCES: 1. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Flonase. Prescribing Information. GlaxoSmithKline. August 2007. 3. Nasonex. Prescribing Information. Schering Corporation. May 2010. 4. Beconase AQ. Prescribing Information. GlaxoSmithKline. September 2008. 5. Nasacort AQ. Prescribing Information. Sanofi-Aventis U.S. LLC. October 2008. 6. Omnaris. Prescribing Information. Sepracor Inc. May 2010. 7. Rhinocort Aqua. Prescribing Information. AstraZeneca. July 2007. 8. Veramyst. Prescribing Information. GlaxoSmithKline. September 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Injectable/Infusible Biological Agents Prior Authorization Criteria PREFERRED STATUS: Preferred Biological Agents. Require prior authorization ENBREL (etanercept): 25 mg vial, 50 mg/ml single-use prefilled syringe HUMIRA (adalimumab): 40 mg/0.8 ml kit, available as pen or syringe, 20 mg prefilled syringe REMICADE (infliximab): 100 mg/20 ml vial XELJANZ (tofacitinib): 5mg Tablet PREFERRED STATUS: Non-Preferred Biological Agents. Require prior authorization (Second Line) ACTEMRA (tocilizumab): 20 mg/ml preservative-free single-use vial CIMZIA (certolizumab): 200 mg lyophilized powder for injection KINERET (anakinra):100 mg/0.67 ml prefilled glass syringe ORENCIA (abatacept): 250 mg preservative-free, 125 mg single-use prefilled syringe SIMPONI TM (golimumab): 50 mg/0.5 ml vial STELARA TM (ustekinumab): 45 mg/0.5 ml vial PA CRITERIA FOR APPROVAL FOR RHEUMATOID ARTHRITIS: The patient is an adult ( 18 y/o) and has a documented clinical diagnosis of rheumatoid arthritis. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) of 3 months or more of therapy with methotrexate AND then leflunomide (generic Arava ) or another disease-modifying antirheumatic drug (DMARD) option (i.e. combination therapy consisting of methotrexate + sulfasalazine or hydroxychloroquine) or has a documented medical reason (e.g. intolerance, hypersensitivity) for not utilizing any of these therapies to manage their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with rheumatoid arthritis and is being recommended and prescribed by a rheumatologist at an FDA-approved dosage If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of two of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR ANKYLOSING SPONDYLITIS The patient is an adult ( 18 y/o) and has documented ankylosing spondylitis. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of or has a documented medical reason for not taking at least two nonsteroidal anti-inflammatory drugs (NSAIDS) to manage their medical condition. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of or has a documented medical reason for not taking a cyclo-oxygenase (COX)-2-selective inhibitors to manage their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with ankylosing spondylitis and is being recommended and prescribed by a rheumatologist at an FDA approved dosage If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of two of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR CROHN S DISEASE: The member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn s disease. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) at therapeutic doses or has a documented clinically significant medical reason for not receiving conventional oral therapy (e.g. azathioprine, corticosteroids, 6-mercaptopurine) to manage their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with moderate to severe active Crohn s disease and is being recommended and prescribed by a gastroenterologist at an FDA-approved dosage If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of one of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS: The patient is a child (< 17 y/o), within the FDA approved age range for the medication requested, and has a documented clinical diagnosis of juvenile idiopathic arthritis.

The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) of 2 months or more of therapy with at least one disease-modifying antirheumatic drug (DMARD) (e.g. methotrexate), or has a documented medical reason (e.g. intolerance, hypersensitivity) for not utilizing any of these therapies to manage their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with juvenile idiopathic arthritis and is being recommended and prescribed by a rheumatologist or a pediatric rheumatologist at an FDA-approved dosage. If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of two of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS: The patient is a child (< 17 y/o), within the FDA approved age range for the medication requested, and has a documented clinical diagnosis of systemic juvenile idiopathic arthritis. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with systemic juvenile idiopathic arthritis and is being recommended and prescribed by a rheumatologist or a pediatric rheumatologist at an FDA-approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR PSORIASIS: The member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severe plaque psoriasis. Documentation that the patient has had (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trials (including dates and doses) of at least 3 of the treatment bullet points listed below: o o o o o o The use of topical steroids or has a documented medical reason for not using this therapy to manage their medical condition The use of a topical medication [i.e. Dovonex (calcipotriene), Tazorac (tazorotene), anthralin or a coal tar preparation] that is indicated for the treatment of psoariasis or has a documented medical reason for not using any of these therapies to manage their medical condition The use of methotrexate or has a documented medical reason (e.g. history of liver or kidney disease, pregnancy, severe cytopenia, alcoholism) for not using this therapy to manage their medical condition The use of cyclosporine or has a documented medical reason for not using this therapy to manage their medical condition The use of Soriatane (acitretin) or has a documented medical reason for not using this therapy to manage their medical condition The use of UVB phototherapy or PUVA (psoralen oral or topical methoxsalen plus UVA therapy) or has a documented medical reason (e.g. pregnancy, skin cancer, hypersensitivity due to preexisting disease state - e.g. systemic lupus erythematus, cataracts) for not undergoing UVB phototherapy or PUVA to manage their medical condition Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has an FDA approved indication for use in patients with moderate to severe plaque psoriasis and is being recommended or prescribed by a dermatologist at an FDA-approved dosage. If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of two of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6 month duration (except for Amevive). If the request is for Amevive, the request will be approved for a 1 month duration with additional monthly authorizations (up to 3 months of total treatment) after receiving documentation that the member s CD4+ T-lymphocyte counts are 250 cells/µl; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR PSORIATIC ARTHRITIS (PsA) The patient is an adult ( 18 y/o) and has documented psoriatic arthritis. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of 2 g/day for 3 months of sulfasalazine or has a documented medical reason for not taking sulfasalazine (e.g. predominantly axial symptoms, hepatotoxicity, GI intolerance) to manage their medical condition. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (3 months without any improvement at maximum doses) of methotrexate or has another documented medical reason for not taking methotrexate (e.g. predominantly axial symptoms, liver toxicity) to manage their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has a FDA approved indication for use in patients with psoriatic arthritis and is being recommended and prescribed by a rheumatologist or a dermatologist at an FDA-approved dosage. If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of two of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a clinical reviewer for medical necessity review. PA CRITERIA FOR APPROVAL FOR USE IN ULCERATIVE COLITIS:

The patient is an adult ( 18 y/o) and has moderate to severe active ulcerative colitis. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) treatment failure after receiving an adequate trial of: o Sulfasalazine (3 to 6 g/day for 3 months), or mesalamine (1.2 to 2.4 g/day for 3 months), or azathioprine (2 to 2.5 mg/kg/day), or 6- mercaptopurine (1.5 to 2 mg/kg/day), or oral corticosteroids or has a documented medical reason (GI intolerance, hypersensitivity, etc.) for not taking any of these medications to treat their medical condition. Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). The medication requested has a FDA approved indication for use in patients with moderate to severe active ulcerative colitis and is being prescribed at an FDA-approved dosage and is recommended or prescribed by a gastroenterologist. If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of one of the preferred biological agents. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR RHEUMATOID ARTHRITIS: The member has been receiving the medication and documentation was provided that a rheumatologist has evaluated the member and recommends continuation of therapy. Documentation submitted indicates that the member has obtained significant clinical benefit from the medication. For members who require Humira 40 mg SC weekly documentation must be submitted indicating that the member was compliant (consistent with pharmacy claims) with receiving at least 16 weeks of continuous Humira therapy every other week prior to the request for weekly dosing of Humira AND the member has a medical reason (e.g. intolerance, hypersensitivity, contraindication) for not receiving concomitant methotrexate. The medication is being prescribed for an FDA-approved indication at an FDA-approved dosage. If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medications; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR ANKYLOSING SPONDYLITIS, CROHN S DISEASE, SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS, POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS, PSORIATIC ARTHRITIS or ULCERATIVE COLITIS: The medication is being recommended and prescribed by a dermatologist, gastroenterologist, rheumatologist, or a pediatric rheumatologist for an FDA-approved indication at an FDA-approved dosage. The member has been receiving the medication and documentation was provided that the prescriber has evaluated the member and recommends continuation of therapy. Documentation submitted indicates that the member has obtained significant clinical benefit from the medication. If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medications; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR PSORIASIS: The medication is being recommended and prescribed by a dermatologist, gastroenterologist, rheumatologist, or a pediatric rheumatologist at an FDA-approved dosage. The member has been receiving the medication and documentation was provided that the prescriber has evaluated the member and recommends continuation of therapy. Documentation submitted indicates that the member has obtained significant clinical benefit from the medication. If all of the above conditions are met, the request will be approved for a 6-month duration for Remicade requests and for a 12 month duration for requests for all other medication (except Amevive). If the request is for Amevive, the request will be approved for a 1 month duration with additional monthly authorizations (up to 3 months of total treatment ) after receiving documentation that the member s CD4+ T-lymphocyte counts are 250 cells/µl. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR OTHER NON-FDA APPROVED MEDICALLY ACCEPTED INDICATIONS: The medication is prescribed for a non-fda approved indication that is considered a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints, AHFS drug information) as defined by the Social Security Act. The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act. The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard of care guidelines or has another documented medical reason (e.g. intolerance, contraindications) for not receiving or trying all first line medical treatment(s). Documentation was submitted indicating that the member was evaluated for active or latent TB infection (i.e. tuberculin skin test). If the request is for a non-preferred agent, documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial of at least two preferred biological agents (if possible). If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review.

PA CRITERIA FOR RE-AUTHORIZATION FOR OTHER NON-FDA APPROVED MEDICALLY ACCEPTED INDICATIONS: Documentation that the medication is recommended or prescribed by a specialist for the respective treated disease state and is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints, AHFS) as defined by the Social Security Act. The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. Documentation submitted indicates that the member has obtained significant clinical benefit from the medication. FDA INDICATIONS: If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. Actemra Cimzia Enbrel Humira Kineret Orencia Remicad e Simponi Stelara Xeljanz Ankylosing Spondylitis X X X X Crohn's Disease X X X ( 6 y.o.) Systemic Juvenile Idiopatic Arthritis X ( 2 y.o.) Psoriasis X X X X Psoriatic Arthritis X X; +/- MTX X; +/- MTX or other DMARD X X +/- MTX X Rheumatoid Arthritis X; monotx or concomit ant use with a nonbiological DMARD X X; +/- MTX X; +/- MTX or other DMARD X; monotx or concomit ant use with a non-tnfblocker DMARD X; monotx or concomit ant use with a non-tnfblocker DMARD X; with concomit ant MTX X; with concomit ant MTX X Ulcerative Colitis X X X Polyarticular Juvenile Idiopathic Arthritis X ( 2 y.o.) X ( 2 y.o.) X ( 4 y.o.) X ( 6 y.o.); monotx or + MTX Actemra is indicated for: treatment of moderately- to severely-active rheumatoid arthritis in adult patients who have had an inadequate response to one or more TNF antagonist. It can be used as monotherapy or in combination with nonbiological disease-modifying antirheumatic drugs (DMARDs). treatment of active systemic juvenile idiopathic arthritis in patients 2 years of age and older. Treatment of active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. Cimzia is indicated for: reducing signs and symptoms of Crohn s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy Treatment of adults with moderately to severely active rheumatoid arthritis Treatment of adult patients with active psoriatic arthritis Enbrel is indicated for: reduction in signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately- to severely-active rheumatoid arthritis. It can be used either alone or in combination with MTX reducing signs and symptoms of moderately- to severely-active polyarticular juvenile idiopathic RA in pediatric patients who are ages 2 and older

reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis. It can be used either alone or in combination with MTX; treatment of adult patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy reducing signs and symptoms in adult patients with active ankylosing spondylitis Humira is indicated for: reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (as monotherapy or in combination with methotrexate or other DMARDs) reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis (as monotherapy or in combination with DMARDs) reducing signs and symptoms in adult patients with active ankylosing spondylitis reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn s disease who have not adequately responded to conventional therapy or for reducing signs and symptoms and inducing clinical remission in these Crohn s disease patients if they have also lost response to or are intolerant to Remicade (infliximab) treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older (as monotherapy or in combination with methotrexate) inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants (effectiveness has not been established in patients who have lost response or were intolerant to ant-tnf agents) Kineret is indicated for: treatment of moderately- to severely-active rheumatoid arthritis in adult patients who have failed one or more disease-modifying antirheumatic drugs (DMARDs). It may be used alone or in combination with DMARDs (other than tumor necrosis factor-blocking agents) Orencia is indicated for: treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA). It may be used as monotherapy or in combination with methotrexate Note: Orencia (abatacept) should not be used in combination with Kineret (anakinra) or TNF-blocking agents. Remicade is indicated for: use in combination with methotrexate for the reduction of signs and symptoms, to inhibit the progression of structural damage, and the improvement of physical function in patients with moderately to severely active rheumatoid arthritis reduction of signs and symptoms and to induce and maintain clinical remission in adult and pediatric patients with moderately to severely active Crohn s disease who have had an inadequate response to conventional therapy reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn s disease reduction of signs and symptoms of active arthritis, to inhibit the progression of structural damage, and to improved physical function in patients with psoriatic arthritis reducing signs and symptoms, achieving clinical remission (without the continued use of steroids) and mucosal healing, in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy treatment to reduce signs and symptoms in adult patients with active ankylosing spondylitis treatment of adult patients with chronic severe plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate Simponi is indicated for: treatment of adult patients with moderately to severely active rheumatoid arthritis in combination with methotrexate treatment of adult patients with active psoriatic arthritis, either as monotherapy or in combination with methotrexate treatment of adult patients with active ankylosing spondylitis Treatment of adult patients with moderate to severe Ulcerative colitis (UC) with an inadequate response or intolerant to prior treatment or requiring continuous steroid therapy Stelara is indicated for: treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy treatment of adult patients with active psoriatic arthritis, alone or in combination with methotrexate Xeljanz is indicated for: treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). DOSAGE AND ADMINISTRATION: Actemra:

Rheumatoid Arthritis: The recommended starting dose of Actemra is 4 mg/kg, followed four weeks later by an increase to 8 mg/kg based on clinical response. Actemra is administered once every four weeks as a 60-minute single intravenous drip infusion. Doses exceeding 800 mg per infusion are not recommended. Sytemic Juvenile Idiopathic Arthritis (SJIA): The recommended dose of Actemra is, given once every 2 weeks as a 60-minute single intravenous drip infusion: Recommended SJIA Dosage Every 2 Weeks Patient less than 30 kg weight Patients at or above 30 kg weight 12 mg per kg 8 mg per kg Polyarticular Juvenile Idiopathic Arthritis (PJIA): The recommended dose of Actemra is, given once every 4 weeks as a 60-minute single intravenous drip infusion: Recommended PJIA Dosage Every 4 Weeks Patient less than 30 kg weight Patients at or above 30 kg weight 10 mg per kg 8 mg per kg Cimzia: Crohn s Disease: The recommended initial adult dose of Cimzia is 400 mg, given as 2 subcutaneous injections of 200 mg each initially and at weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every 4 weeks. Rheumatoid Arthritis: The recommended dose of Cimzia for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, Cimzia 400 mg every 4 weeks can be considered. Psoriatic Arthritis: The recommended dose of Cimzia for adult patients is 400mg initially and at week 2 and 4, followed by 200mg every other week. For maintenance dosing, Cimzia 400mg every 4 week can be considered. Enbrel: Ankylosing Spondylitis, adult RA, and Psoriatic Arthritis: The recommended dose of Enbrel is 50 mg per week, given as either a single subcutaneous injection or (2) 25 mg subcutaneous injections. Methotrexate, glucocorticoids, salicylates, nonsteroidal antiinflammatory drugs (NSAIDs), or analgesics may be continued during treatment. Psoriasis: The recommended starting dose of Enbrel for adult patients is a 50 mg dose given twice weekly (administered 3 or 4 days apart) for 3 months followed by a reduction to a maintenance dose of 50 mg per week according to clinical studies. Starting doses of Enbrel 25 mg or 50 mg per week were also shown to be efficacious. Juvenile Arthritis: The recommended dose of Enbrel for children 2 to 17 years of age with active polyarticular-course JRA is 0.8 mg/kg (up to a maximum of 50 mg per week). The 25 mg prefilled syringes are not recommended for pediatric patients weighing less than 31 kg (68 pounds). The 50 mg prefilled syringe or SureClick autoinjector may be used for pediatric patients weighing 63kg (138 pounds) or more. Glucocorticoids, NSAIDs, or analgesics may be continued during treatment with Enbrel. Concurrent use of MTX and higher doses of Enbrel have not been studied in pediatric patients. Humira: RA, Psoriatic Arthritis or Ankylosing Spondylitis: The recommended dose of Humira for adult patients is 40 mg administered every other week as a subcutaneous injection. Methotrexate (MTX), glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, or other DMARDs may be continued during treatment with Humira. For RA, some patients not taking concomitant MTX, may derive additional benefit from increasing the dosing frequency of Humira to 40 mg SC every week. Crohn s Disease: The recommended dose of Humira for adult patients is on day 1 to give 160 mg (four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later (on day 15), then two weeks after that (on day 29) begin the maintenance dose therapy of 40 mg every other week. Aminosalicylates or corticosteriods maybe continued during treatment with Humira. Azathioprine, 6-mercaptopurine (6-MP) or methotrexate may be continued during treatment with Humira if necessary. The use of Humira in Crohn s disease beyond one year has not been evaluated in controlled clinical studies. Juvenile Idiopathic Arthritis: The recommended dose of Humira for patients 4 to 17 years of age with polyarticular juvenile idiopathic arthritis is based on weight: Pediatric Patients (4 to 17 years) Dose: 15 kg (33 lbs) to < 30 kg (66 lbs): 20 mg every other week 30 kg (66 lbs): 40 mg every other week Methotrexate (MTX), glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment with Humira. Limited data is available for Humira treatment in pediatric patients who weigh less than 15 kg. Plaque Psoriasis: The recommended dose of Humira is a 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Ulcerative Colitis: The recommended dose of Humira is 160 mg initially on day 1 (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later (day 15). Two weeks later (day 29) continue with a dose of 40 mg every other week. Humira should be continued only if patients have evidence of clinical remission by week 8. Kineret:

Rheumatoid Arthritis: The recommended dose is 100 mg/day administered daily by subcutaneous injection. Administer Kineret at the same time every day. Higher doses did not result in a higher response. Orencia: Rheumatoid arthritis: Orencia should be administered as a 30-minute intravenous (IV) infusion at the dose specified in the following table. Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter. Orencia Dosing Body weight < 60 kg 60 to 100 kg > 100 kg Dose 500 mg 750 mg 1 g 4 Number of 250 mg vials Juvenile Idiopathic Arthritis (JIA): The recommended dose of Orencia for patients age 6 to 17 years with JIA who weigh less than 75 kg is 10 mg/kg calculated based on the patient s body weight at each administration. Pediatric patients weighing 75 kg or more should be administered Orencia following the adult dosing regimen, not to exceed a maximum dose of 1000 mg. Orencia should be administered as a 30-minute intravenous (IV) infusion at the dose specified in the table above. Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion, then every 4 weeks thereafter. Remicade: Rheumatoid Arthritis: 3 mg/kg given as an IV infusion followed with additional 3 mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. Give Remicade in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/kg or treating as often as every 4 weeks (keeping in mind that at higher dosages there is an increase risk of serious infections). Crohn's Disease or Fistulizing Crohn s Disease: 5 mg/kg given as an induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. For patients who respond and then lose their response, consider treatment with 10 mg/kg. Patients who do not respond by week 14 are unlikely to respond with continued dosing; consider discontinuing Remicade in these patients. Psoriatic Arthritis and Plaque Psoriasis: The recommended dose is 5 mg/kg followed with additional 5 mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. For the treatment of psoriatic arthritis, Remicade can be used with or without methotrexate. Ankylosing Spondylitis: The recommended dose is 5 mg/kg followed with additional 5 mg/kg doses at 2 and 6 weeks after the first infusion, then every 6 weeks thereafter. Ulcerative Colitis: 5 mg/kg given as an induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active ulcerative colitis. Simponi: Rheumatoid Arthritis: The recommended dose is 50 mg administered by subcutaneous (SC) injection once a month. For patients with rheumatoid arthritis, Simponi should be given in combination with methotrexate. Corticosteroids, non-biologic DMARDs, or NSAIDs may be continued during treatment with Simponi. Psoriatic Arthritis and Ankylosing Spondylitis: The recommended dose is 50 mg administered by subcutaneous (SC) injection once a month. For patients with psoriatic arthritis or ankylosing spondylitis, Simponi may be given with or without methotrexate or other non-biologic DMARDs. Corticosteroids, non-biologic DMARDs, or NSAIDs may be continued during treatment with Simponi. Ulcerative Colitis: 200mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100mg at Week 2 and then 100mg every 4 weeks Stelara: Psoriasis: For patients weighing <100 kg (220 lbs), the recommended dose is 45 mg administered by subcutaneous injection initially and 4 weeks later, followed by 45 mg every 12 weeks. For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. In subjects weighing >100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects. Psoriatic Arthritis: The recommended dose is 45mg initially and 4 weeks later, followed by 45mg every 12 weeks. For patients with co-existent moderate-to-severe plaque psoriasis weighing >100ks (220 lbs), the recommended dose is 90mg initially and 4 weeks later, followed by 90mg every 12 weeks. Xeljanz: Rheumatoid Arthritis: 5mg twice daily REFERENCES: 1. Guidelines for the Management of Rheumatoid Arthritis; American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines; 2008 Update. Arthritis and Rheumatism 2008; 59(6): 762-84. 2. Humira Prescribing Information. Abbott Laboratories,. 09/2013. 3. Enbrel Product Information. Immunex Corporation. 09/2013. 4. Cimzia Prescribing Information. UCB, Inc.. 09/2013. 2 3

5. Orencia Prescribing Information. Bristol-Myers Squibb. 07/2013. 6. Actemra Prescribing Information. Genentech, Inc. April 2013. 7. Kineret Prescribing Information. Biovitrum. 12/2012. 8. Remicade Prescribing Information. Centocor Ortho Biotech, Inc. 03/2013. 9. Simponi Prescribing Information. Centocor Ortho Biotech, Inc. May 2013. 10. Stelara Prescribing Information. Centocor Ortho Biotech, Inc. 09/2013. 11. Xeljanz Prescribing Information. Pfizer, Inc. November 2012. 12. Saini R. Tutrone WD. Weinberg JM. Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus. Current Pharmaceutical Design. 11(2): 273-80, 2005. 13. Callen JP, Krueger GG, et al. AAD consensus statement on psoriasis therapies; Journal of the American Academy of Dermatology 2003; 49:897-9. 14. Linden KG. Weinstein GD. Psoriasis: current perspectives with an emphasis on treatment. American Journal of Medicine. 107(6): 595-605, 1999 Dec. 15. Lebwohl M, Menter A, Koo J, Feldman R. Combination therapy to treat moderate to severe psoriasis; Journal of the American Academy of Dermatology 2004; 50:416-430. 16. Pardasani A, Feldman S, Clark A. Treatment of Psoriasis: An Algorithm-Based Approach for Primary Care Physicians. American Family Physician 2000;61(3):725-733. 17. Saini R. Tutrone WD. Weinberg JM. Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus. Current Pharmaceutical Design. 11(2):27f3-80, 2005. 18. Salvarani C, Cantini F, Olivieri I. Disease-Modifying Antirheumatic Drug Therapy for Psoriatic Arthritis. Clinical and Experimental Rheumatology 2002; 20(S28):S71-75. 19. Peyrin-Biroulet L, Laclotte C, Bigard M.A. Adalimumab Maintenance Therapy for Crohn s Disease with Intolerance or Lost Response to Infliximab: an open-label study; Alimentary Pharmacology & Therapeutics 2007; 25: 675-680. 20. Colombel J.F., Sandborn W, et. al. Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn s Disease: The CHARM Trial; Gastroenterology 2007: 132: 52-65 21. Braun J, Pham T, Sieper J, et.al. International ASAS consensus statement for the use of anti-tumor necrosis factor agents in patients with ankylosing spondylitis; Ann Rheum Dis 2003; 62: 817-24. 22. Zochling Z, van der Heijde D, Burgos-Vargas R, et. al. ASAS/EULAR recommendations for the Management of Ankylosing Spondylitis; Ann Rheum Dis 2006; 65: 442-52. 23. Nast A, Kopp A, Augustin M, et al. German-evidence-based guidelines for the treatment of Psoriasis vulgaris (short version). Arch Dermatol Res 2007: 299: 111-138. 24. Sandborn WJ, Feagan BG, Marano CW, et al. A phase 2/3 randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of subcutaneous golimumab induction therapy in patients with moderately to severely active ulcerative colitis: PURSUIT SC [abstract]. Digestive Disease Week, May 19-22. San Diego, California. Late Breaking Abstract Session. Abstract 943d. 25. Sandborn WJ, Faegan BG, Marano CW, et al. A phase 3 randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of subcutaneous golimumab maintenance therapy in patients with moderately to severely active ulcerative colitis: PU*RSUIT maintenance [abstract]. American College of Gastroenterology, October 19-24, 2012. Las Vegas, Nevada. Late Breaking Abstract Session. 26. Brunner HI, Ruperto N, Zuber Z, et al. Efficacy and safety of tocilizumab in patients with polyarticular juvenile idiopathic arthritis: data from a Phase 3 trial. Presented at the American College of Rheumatology in Washington DC; November 9-14, 2012. ACR Abstract #1597. 27. Brunner HI, Ruperto N, Zuber Z et al. Efficacy and safety of tocilizumab in patients with poly articular-course Juvenile Idiopathic Arthritis: data from a Phase 3 trial. Presented at the American College of Rheumatology Annual Scientific Meeting in Washington DC: November 9-14, 2012. ACR Oral presentation. Revision/Review Date: 11/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION CRITERIA Injectable/Infusible Osteoporosis Agents Prior Authorization Criteria BONIVA INJECTION (ibandronate sodium): 3 mg/3ml single use syringe FORTEO (teriparatide [rdna origin] injection): 20mcg/dose in a 2.4ml prefilled pen PROLIA (denosumab): 60 mg/1ml RECLAST (zoledronic acid): 5 mg/100ml PA CRITERIA FOR APPROVAL FOR USE IN OSTEOPOROSIS: Documentation was submitted which places the member into one of the following categories: 1) Postmenopausal woman or a male patient who has a bone mineral density (BMD) value consistent with osteoporosis (i.e., T- scores equal to or less than 2.5) or who has had an osteoporotic fracture. 2) Postmenopausal woman or man over 50 with a T-score between -1 and -2.5 at the femoral neck or spine and a 10 year hip fracture probability >3% or a 10 year major osteoporosis-related fracture probability >20% based on the US-adapted WHO absolute fracture risk model. The patient has a documented (consistent with pharmacy claims data) treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of therapy) or has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing these therapies to manage their medical condition: o An oral bisphosphonate The patient is taking adequate Calcium and Vitamin D supplementation. If the request is for Boniva (ibandronate sodium) Injection or Prolia (denosumab), there must be a documented trial and failure or intolerance to Reclast (zoledronic acid) in females. If the request is for Forteo (teriparatide [rdna origin] injection), there must be a documented trial and failure or intolerance to Reclast (zoledronic acid) and then either Boniva Injection (ibandronate sodium) or Prolia (denosumab) in females or Reclast (zoledronic acid) in males. If the request is for Reclast, documentation of patient s serum creatinine and creatinin clearance > 35mL/min must be submitted. The medication requested has a FDA approved indication for use in patients with osteoporosis and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and for all other medications the request will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-APPROVAL FOR USE IN OSTEOPOROSIS: The patient has documentation of clinical benefit from the medication. The patient is taking adequate Calcium and Vitamin D supplementation. If the request is for Forteo (teriparatide [rdna origin] injection): o The prescribed dosage is within the FDA approved dosage range and does not exceed the therapy maximum of 2 years as indicated below under dosage and administration. o The medication requested has a FDA approved indication for use in patients with osteoporosis and is being recommended and prescribed at a FDA approved dosage. If the request is for Reclast, documentation of patient s serum creatinine and creatinin clearance > 35mL/min must be submitted. If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and for all other medications the request will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR USE IN THE TREATMENT OR PREVENTION OF OSTEOPOROSIS DUE TO GLUCOCORTICOID THERAPY: Documentation, including for what indication the patient will be, or is currently utilizing glucocorticoid therapy for a minimum of 12 months. Documentation that the dosage of the glucocorticoid therapy is equivalent to a dose > 7.5 mg of prednisone daily if the request is for Reclast or >5 mg if the request is for Forteo. Documentation (consistent with pharmacy claims data) of treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of therapy) or a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing an oral bisphosphonate to manage their medical condition. If the request is for Reclast, documentation of patient s serum creatinine and creatinin clearance > 35mL/min must be submitted. The medication requested has a FDA approved indication for use in patients for the treatment or prevention of osteoporosis and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request for Forteo will be approved for a 6-month duration and Reclast will be approved for a 12-month duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR INITIAL APPROVAL IN PATIENTS WITH PAGET S DISEASE: Documentation of a confirmed diagnosis of Paget s disease.

Documentation (consistent with pharmacy claims data) of treatment failure after receiving an adequate trial of the following therapies (including dates of treatment at maximum recommended doses of therapy) or the patient has a documented medical reason (intolerance, hypersensitivity, contraindication, etc) for not utilizing an oral bisphosphonate to manage their medical condition. Documentation (from within 60 days of the request) that the patient has a serum alkaline phosphatase level of > two times the upper limit of normal OR the patient is symptomatic OR the patient is at risk for complication from Paget s disease. The patient is taking adequate Calcium and Vitamin D supplementation. If the request is for Reclast, documentation of patient s serum creatinine and creatinin clearance > 35mL/min must be submitted. The medication requested has a FDA approved indication for use in patients with Paget s disease and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request will be approved; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE - APPROVAL IN PATIENTS WITH PAGET S DISEASE: Documentation of a confirmed diagnosis of Paget s disease. The patient is taking adequate Calcium and Vitamin D supplementation. If the patient is in need of redosing less than 6 months after their initial treatment: documentation (from within 60 days of the request) that the patient s serum alkaline phosphatase level has risen to > two times the upper limit of normal and/or never normalized after the initial treatment OR the patient is suffering from symptoms of Paget s disease is required. If the request is for Reclast, documentation of patient s serum creatinine and creatinin clearance > 35mL/min must be submitted. The medication requested has a FDA approved indication for use in patients with Paget s disease and is being recommended and prescribed at a FDA approved dosage. If all of the above conditions are met, the request will be approved; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR APPROVAL FOR USE IN CANCER TREATMENT BONE LOSS DUE TO HORMONE ABLATION: Documentation submitted which places the member into one of the following categories: 1. Men at high risk for fracture receiving androgen depravation therapy for nonmetastic prostate cancer a. Documentation must be submitted that the patient has accomplished androgen deprivation therapy by either bilateral orchiectomy (surgical castration), a lutenizing-hormone releasing hormone antagonist (medical castration), or taking a luteinizing-hormone releasing hormone/gonadotropin-releasing hormone (GnRH) agonist 2. Woman at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer a. Documentation must be submitted that the patient is currently take either anastrozole (Arimidex ), letrozole (Femara ), or exemestane (Aromasin ) If all of the above conditions are met, the request will be approved; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA INDICATION: Indication Boniva injection Forteo Prolia Reclast Osteoporosis in postmenopausal women X X X X Osteoporosis in men X X X Treatment of osteoporosis due to glucocorticoid therapy X X Prevention of osteoporosis due to glucocorticoid therapy X Paget s disease X To increase bone mass in men at risk for fracture receiving androgen deprivation therapy for X prostate cancer To increase bone mass in women at risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer X FDA INDICATION: Boniva injection is indicated for: Treatment of osteoporosis in postmenopausal women. Reclast is indicated for:

The treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, Reclast reduces the incidence of fractures (hip, vertebral, and non-vertebral osteoporosis-related fractures). The prevention of osteoporosis in postmenopausal women. The treatment to increase bone mass in men with osteoporosis. The treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage > 7.5 mg per day of prednisone and who are expected to remain on glucocorticoids for at least 12 months. The treatment of Paget s disease of bone in men and women. Treatment is indicated for patient s wit Paget s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease. Forteo injection is indicated: For the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, or who have failed or are intolerant of previous osteoporosis therapy. To increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. These include men with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant to previous osteoporosis therapy. Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia is indicated for: For the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures. Treatment to increase bone mass in men with osteoporosis Treatment to increase bone mass in men at high risk for fractures receiving androgen deprivation therapy for nonmetastic prostate cancer. Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. DOSAGE AND ADMINISTRATION: Boniva: Osteoporosis in Postmenopausal Women: The recommended dose is 3 mg IV given once every 3 months Forteo: Osteoporosis in Postmenopausal Women/Men & Treatment and Prevention of Glucocorticoid-Induced Osteoporosis: The recommended dosage is 20 mcg once a day administered as a subcutaneous injection into the thigh or abdominal wall. The length of therapy should be no longer than 2 years. Prolia: Osteoporosis in Men & Postmenopausal Women, Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer & Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer: The recommended dose is 60 mg administered as a single subcutaneous injection once every 6 months administered via subcutaneous injection in the upper arm, the upper thigh, or the abdomen. All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily. If a dose of Prolia is missed, administer the injection as soon as the patient is available. Thereafter, schedule injections every 6 months from the date of the last injection. Reclast: Treatment of Postmenopausal Osteoporosis/ Osteoporosis in Men & the Treatment and Prevention of Glucocorticoid-Induced Osteoporosis: The recommended dose is a 5 mg infusion once a year given intravenously over no less than 15 minutes. Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. An average of at least 1200 mg of calcium and 800-1000 IU of vitamin D daily is recommended. Prevention of Osteoporosis in Postmenopausal Women: The recommended regimen in a 5 mg infusion given once every 2 years intravenously over no less than 15 minutes. Patients must be adequately supplemented with calcium and vitamin D if dietary intake is not sufficient. Postmenopausal women require an average of 1200 mg calcium and 800-1000IU vitamin D daily. Paget s Disease of the Bone: The recommended dose is a 5 mg infusion. The infusion must be given over a constant infusion rate of no less than 15 minutes. Reference: 1. Boniva Injection Prescribing Information. GlaxoSmithKline, 04/2013. 2. Forteo Prescribing Information. Eli Lilly and Company, 03/2012. 3. Prolia Prescribing Information. Amgen, 09/2012.

4. Reclast Prescribing Information. Novartis, 04/2013. 5. Dawson-Hughes B. Lindsay R, Khosla S. Et al. Physician s Guide to Prevention and treatment of osteoporosis. Developed by the National Osteoporosis Foundation in collaboration with American Academy of Orthopedic Surgeons, American Academy of Physical Medicine and Rehabilitation, American College of Obstetricians and Gynecologists, American College of Radiology, American College of Rheumatology, American Geriatrics Society, American Medical Association, International Society for Physical Medicine and Rehabilitation and The Endocrine Society. Updated 2008. 6. National Osteoporosis Foundation. Physician s guide to prevention and treatment of osteoporosis. http://www.nof.org/sites/default/files/pdfs/nof_clinicianguide2009_v7.pdf. Accessed February 8, 2011. 7. Black DM, Delmas PD, Eastell R, et al. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. N Eng J Med 2007; 356(18): 1809-22. 8. McClung M, Recker R, Miller P, et al. Intravenous Zoledronic Acid 5 mg in the Treatment of Postmenopausal Women with Low Bone Density Previously Treated with Alendronate. Bone 2007; 45: 122-8. 9. Reid IR, Miller P, Lyles K, et al. Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget s Disease. N Eng J Med 2005; 353: 898-908. 10. Siris ES, Lyles KW, Singer FR, Meunier PJ. Medical Management of Paget s Disease of Bone: Indications of Treatment and Review of Current Therapies. J Bone and Mineral Research 2006; 21(S2): 94-8. 11. Binkley N. Krueger D. Current osteoporosis prevention and management. Topics in Geriatric Rehabilitation. 2004; 21(1):17-29. 12. Olszynski WP, Davison KS, Adachi JD, et al. Osteoporosis in Men: Epidemiology, Diagnosis, Prevention, and Treatment. Clinical Therapeutics 2004; 26(1): 15-28. 13. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. 14. Smith MR, Egerdie B, Toriz NH, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl Med. 2009 Aug 20;361(8): 745-55. 15. Ellis, GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008 Oct 20;25:4875-82. 16. NCCN Clinical Practice Guidelines in Oncology : Prostate Cancer; V.2.2013 Update. 17. NCCN Clinical Practice Guidelines in Oncology : Breast Cancer; V.3.2013 Update. Revision/Review Date: 06.2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA for INTRAVENOUS IMMUNOGLOBULIN USE in MULTIPLE SCLEROSIS PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): Documentation submitted indicates that the member is an adult ( 18 y/o) and has a clinical diagnosis of relapsing-remitting MS (not primary or secondary MS). Documentation submitted including patient current weight Clinical and/or diagnostic information was submitted that indicates that the patient has a documented (consistent with pharmacy claims data OR for new members to the health plan consistent with medical chart history) treatment failure (see Box 1 for definition of treatment failure) after receiving an adequate trial (including dates, doses of 6 months or more of each therapy) of 3 out of the 5 following self-injectable agents (Rebif (interferon Beta- 1A), Betaseron or Extavia (interferon Beta 1B), Avonex (interferon Beta 1A) and Copaxone (glatiramer acetate)) OR has a some other documented medical reason (intolerance, hypersensitivity, etc) for not utilizing these therapeutic options for a minimum of 6 months each to manage their medical condition. A letter of medical necessity must be submitted which states: rationale for choosing this medical treatment, expected length and goals of therapy. The medication is being recommended and prescribed by a neurologist at a medically acceptable dosage regimen (see below). If all of the above conditions are met, the request will be approved for up to 4 months; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): Documentation submitted indicates that the member is an adult ( 18 y/o) and has a clinical diagnosis of relapsing-remitting MS (not primary or secondary MS). Documentation submitted including patient current weight Once every 12 months a letter of medically necessity must be submitted which states: improvements that the patient has made while on therapy, expected length and goals of therapy. The medication is being recommended and prescribed by a neurologist at a medically acceptable dosage regimen (see below). If all of the above conditions are met, the request will be approved for up to 4 months; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. DOSAGE AND ADMINISTRATION: Medically Acceptable Dosing for Intravenous Immunoglobulin use in Multiple Sclerosis 0.15-0.2 g/kg of IVIG monthly 0.4 g/kg of IVIG per day for 5 consecutive days and then 0.4 g/kg once every 2 months 1 g/kg per day for 2 days per month GLOSSARY: BOX 1: TREATMENT FAILURE: A member may be considered to have failed treatment if any of the following are documented: 1. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** 2. Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** 3. Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** 4. Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** 5. Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** 6. Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration, mental processing and fatigue. ** 7. Members who have new or enlarging T2 lesions, increase in brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities.**

** These are members who have a documented treatment failure after receiving a minimum of 6 months of either Copaxone, Rebif, Avonex, Extavia, and/or Betaseron. Diagnostic and/or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that the member has failed a minimum of 6 months of (Copaxone, Rebif, Avonex, Extavia, and/or Betaseron) or has a documented medical reason (i.e. intolerance) for not utilizing these therapeutic options for a minimum of 6 months. ** Kurtzke Expanded Disability Scale (EDSS) score: is a scale for evaluating the degree of neurologic impairment in MS. The EDSS score is measured in one-half point increments, from 0.0 (normal) to 10.0 (death). In order to rate a person on the EDSS, the neurologist first performs a standard neurologic examination to test strength, coordination, vision, walking, etc. The neurologist next summarizes the results of the neurological examination in several Functional System Scores as follows: pyramidal (strength and spasticity), cerebella, brain stem, sensory, bowel and bladder, visual, cerebral and other functions. Finally, the neurologist uses the Functional System Scores along with ability to walk to rate the individual on the EDSS. The EDSS score is most reflective of lower limb function. Since this scoring system does not account for other signs and symptoms of MS, it is not used as an absolute measure of disability. But the EDSS can be a good gauge of disease progression. Other scales are used to measure fatigue, symptoms affecting the upper body, and mental changes. Kurtzke Expanded Disability Status Scale (EDSS) Rating Status 0 Normal Neurological Exam 1.0 No Disability, minimal symptoms 1.5 No disability, minimal signs in more than one area 2.0 Slightly more disability in one area 2.5 Slightly greater disability in two areas 3.0 Moderate disability in one area but still walking independently 3.5 Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983; 33:1444-1452. Reference: 1. Aetna, Clinical Policy Bulletins. Available from http://www.aetna.com/cpb/medical/data/200_299/0206.html. Accessed November 2007. 2. Facts & Comparisons Online. Available from http://online.factsandcomparisons.com/monodisp.aspx?monoid=fandchcp11075. Access November 2007. 3. Gurcan HM and Ahmed AR. Efficacy of Various Intravenous Immunoglobulin Therapy Protocols in Autoimmune and Chronic Inflammatory Disorders. Ann Pharmacother 2007; 41: 812-23. 4. Durelli L. and Isoardo G. High-dose intravenous immunoglobulin treatment of multiple sclerosis. Neurol Sci 2002; 23: S39- S48.

5. Sorensen PS, Fazekas F and Lee M. Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis. European Journal of Neurology 2002; 9: 557-63. 6. Lewanska M., Siger-Zajdel M. and Selmaj K. No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment. European Journal of Neurology 2002; 9: 565-72. 7. Fazekas F, Deisenhammer F, Strasser-Fuchs S, et al. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet 1997: 349: 589-93. 8. Fergusson D, Hutton B, Sharma M, et al. Use of Intravenous Immunoglobulin for Treatment of Neurologic Conditions: A Systemic Review. Transfusion 2005; 45: 1640-57. 9. Pohlau D, Przuntek H, Sailer M, et al. Intravenous Immnunoglobulin in Primary and Secondary Chronic Progressive Multiple Sclerosis: A Randomized Placebo Controlled Multicentre Study. Multiple Sclerosis 2007; 13: 1107-17. 10. Haas J, Maas-Enriquez M and Hartung HP. Intravenous Immunoglobulin in the Treatment of Relapsing Remitting Multiple Sclerosis-Results of a Retrospective Multicenter Observational Study Over Five Years. Multiple Sclerosis 2005; 11: 562-67. 11. Sorensen PS. The Role of Intravenous Immunoglobulin in the Treatment of Multiple Sclerosis. Journal of the Neurological Sciences 2003; 206: 123-30. 12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983; 33:1444-52. 13. Rio J. Nos C. Tintore M. et al. Defining the response to interferon-β in RRMS patients. Annals of Neurology.2006; 59:344-352. Revision/Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician review must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA INTUNIV (guanfacine extended-release) Tablet: 1mg, 2mg, 3mg, 4mg STATUS Non-Preferred PA CRITERIA FOR APPROVAL Documented diagnosis of attention deficit hyperactivity disorder (ADHD) Intolerance to at least a three month recent trial of immediate release guanfacine. If the above conditions are met, the request will be approved for 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS For the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications. DOSAGE AND ADMINISTRATION Initial Dose: 1mg per day Maintenance Dose: 1mg to 4mg once daily REFERENCES 1. Intuniv. Prescribing Information. Shire Pharmaceuticals Inc. June 2011. 2. Facts and Comparisons, St. Louis, 2013 efacts CliniSphere Version ISBN 1-57439-036-8. 3. Dobie C, Donald WB, Hanson M, Heim C, Huxsahl J, Karasov R, Kippes C, Neumann A, Spinner P, Staples T, Steiner L. Institute for Clinical Systems Improvement. Diagnosis and Management of Attention Deficit Hyperactivity Disorder in Primary Care for School-Age Children and Adolescents. http://bit.ly/adhd0312. Updated March 2012. Revision/Review Date: 2/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA AMNESTEEM (isotretinoin) Capsules: 10mg, 20mg, 40mg CLARAVIS (isotretinoin) Capsules: 10mg, 20mg,30 mg, 40mg SOTRET (isotretinoin) Capsule: 20mg FORMULARY STATUS: Formulary (generic) PA CRITERIA FOR APPROVAL: Diagnosis of severe recalcitrant nodular acne. AND Documented treatment with a therapeutic trial and failure or intolerance to oral antibiotic therapy first line therapy (e.g. doxycycline, minocycline, tetracycline, erythromycin) for at least 4 weeks (28 days) of therapy in the previous 60 days. If the above conditions are met, the request will be approved for up to a 6 month duration with generic medication; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATION: Isotretinoin is indicated for the treatment of severe recalcitrant nodular acne. Because of significant adverse effects associated with its use, isotretinoin should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, isotretinoin is indicated only for those females who are not pregnant because isotretinoin can cause severe birth defects. DOSAGE AND ADMINISTRATION: Dosage is adjusted and individualized according to side effects and disease response. Recommended course of therapy: Initial dose is 0.5 to 1 mg/kg/day (range is 0.5 to 2 mg/kg/day) divided into 2 doses with food, for 15 to 20 weeks. Failure to take isotretinoin with food will significantly decrease absorption. The safety of once daily dosing has not been established. Once-daily dosing is not recommended. Patients whose disease is very severe or is primarily manifested on the body may require up to the maximum dose. If the total nodule count decreases by > 70% prior to 15 weeks the drug may be discontinued. After a period of > 2 months off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. BLACK BOX WARNING AND ADDITIONAL WARNINGS: Isotretinoin must not be used by females who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking isotretinoin in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected. Birth defects which have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported. Documented external abnormalities include: skull abnormality, ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include: CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases death has occurred with certain of the abnormalities previously noted. If pregnancy does occur during treatment of a female patient who is taking isotretinoin, isotretinoin must be discontinued immediately and she should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Because of isotretinoin s teratogenicity and to minimize fetal exposure, isotretinoin is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called ipledgetm. Isotretinoin must only be prescribed by prescribers who are registered and activated with the ipledge program. Isotretinoin must only be dispensed by a pharmacy registered and activated with ipledge, and must only be dispensed to patients who are registered and meet all the requirements of ipledge. Meeting the requirements for a female patient of childbearing potential signifies that she: Has been counseled and has signed a patient information/informed consent about birth defects form that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin. The patient must sign the informed consent form before starting treatment and patient counseling must also be done at that time and on a monthly basis thereafter. Has had two negative urine or serum pregnancy tests with a sensitivity of at least 25mIU/mL before receiving the initial isotretinoin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for isotretinoin. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests should be at least 19 days. o For patients with regular menstrual cycles, the second pregnancy test should be done during the first 5 days of the menstrual period immediately preceding the beginning of isotretinoin therapy and after the patient has used 2 forms of contraception for one month. o For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, the second pregnancy test must be done immediately preceding the beginning of isotretinoin therapy and after the patient has used 2 forms of contraception for one month. Has had a negative result from a urine or serum pregnancy test in a CLIA-certified laboratory before receiving each subsequent course of isotretinoin. A pregnancy test must be repeated every month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription.

Has selected and has committed to use 2 forms of effective contraception simultaneously, at least one of which must be a primary form, unless the patient commits to continuous abstinence from heterosexual contact, or the patient has undergone a hysterectomy or bilateral oophorectomy, or has been medically confirmed to be post-menopausal. Patients must use two effective forms of effective contraception for at least one month prior to initiation of isotretinoin therapy, during isotretinoin therapy, and for one month after discontinuing isotretinoin therapy. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis. Primary contraception includes: tubal sterilization; partner s vasectomy; intrauterine device; hormonal (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring). Secondary forms include male latex condoms (with or without spermicide), diaphragms, cervical caps, and vaginal sponges all of which must be used with spermicide. Any birth control method can fail. There have been reports of pregnancy from female patients who have used oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products; these pregnancies occurred while these patients were taking isotretinoin. These reports are more frequent for female patients who use only a single method of contraception. There for it is critically important that female patients of childbearing potential use 2 effective forms of contraception simultaneously. Patients must receive written warnings about the rates of possible contraception failure. If a pregnancy does occur during isotretinoin treatment, isotretinoin must be discontinued immediately. The patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure during or one month after isotretinoin therapy must be reported immediately to the FDA via the MedWatch number 1-800- FDA-1088 and also to the ipledge pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com) Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John s Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John s Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John s Wort To receive isotretinoin all patients must meet all of the following conditions: Must be registered with the ipledge program by the prescriber Must understand that severe birth defects can occur with the use of isotretinoin by female patients Must be reliable in understanding and carrying out instructions Must sign a patient information/informed consent (for all patients) form that contains warnings about the potential risks associated with isotretinoin Must fill the prescription within 7 days of the of the date of specimen collection for the pregnancy test for female patients of childbearing potential Must fill and pick up the prescription within 30 days of the office visit for male patients and female patients not of childbearing potential Must not donate blood while on isotretinoin and for one month after treatment has ended Must not share isotretinoin with anyone, even someone who has similar symptoms In addition to the requirements for all patients described above, female patients of childbearing potential must meet the following conditions: Must not be pregnant or breast-feeding Must comply with the required pregnancy testing at a CLIA-certified laboratory Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test Must be capable of complying with the mandatory contraceptive measures required for isotretinoin therapy, or commit to continuous abstinence from heterosexual intercourse, and understand behaviors associated with an increased risk of pregnancy Must understand that it is her responsibility to avoid pregnancy one month before, during, and one month after isotretinoin therapy Must have signed an additional patient information/informed consent about birth defects (for female patients who can get pregnant) form before starting isotretinoin that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin Must access the ipledge program via the internet or telephone before starting isotretinoin, on a monthly basis during therapy, and one month after the last dose to answer questions on the program requirements and to enter the patient s two chosen forms of contraception Must have been informed of the purpose and importance of providing information to the ipledge program should she become pregnant while taking isotretinoin or within one month of the last dose To dispense isotretinoin, pharmacies must be registered and activated with the pregnancy risk management program ipledge. To dispense isotretinoin, the pharmacist must: Be trained by the Responsible Site Pharmacist concerning the ipledge program requirements. Obtain authorization from ipledge via the internet or telephone for every isotretinoin prescription. Authorization signifies that the patient has met all program requirements and is qualified to receive isotretinoin Write the Risk Management Authorization (RMA) number on the prescription. Isotretinoin must only be dispensed: o In no more than a 30-day supply o With an isotretinoin Medication Guide o After authorization from the ipledge program o Prior to the do not dispense to patient after date provided by the ipledge system (within 30 days of the office visit for male patients and female patients not of childbearing potential and within 7 days of the date of specimen collection for female patients of childbearing potential)

o With a new prescription for refills and another authorization from the ipledge program (No automatic refills are allowed) Psychiatric disorders: Isotretinoin may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action had been established for these events. Health care providers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Isotretinoin. Health care providers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of isotretinoin therapy, physicians should ask patients and family members about any history of psychiatric disorder, and at each visit during therapy, assess patients for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. REFERENCES: 1. Is accutane really dangerous? Med Lett Drugs Ther 2002 Sep 16;44(1139):82 2. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of Care for Acne Vulgaris Management. American Academy of Dermatology Association. J Am Acad Dermatol. 2007. Apr;56(4):651-53. 3. Wysowski DK, Swann J, Vega A. Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol 2002 Apr;46(4):505-9. 4. Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol 2003;45 (3S):S200-S210. 5. Enders SJ, Enders JM. Isotretinoin and psychiatric illness in adolescents and young adults. Ann Pharmacother 2003;37 (8): 1124-1127. 6. Young D. FDA, Roche to implement new dispensing procedures for isotretinoin. Am J Health Syst Pharm 2001 Dec 15;58(24):2359-60. 7. Jacobs DG, Deutsch NL,Brewer M. Suicide, depression, and isotretinoin: is there a causal link? J Am Acad Dermatol 2001 Nov;45(5):S168-75. 8. Product information, Amnesteem. Mylan Pharmaceuticals Inc, Revised February 2010. 9. Product information, Claravis. Barr Laboratories Inc, Revised February 2010. 10. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-0368. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

KAPVAY (clonidine extended-release) Tablet: 0.1mg STATUS Non-Preferred PA CRITERIA FOR APPROVAL TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Documented diagnosis of attention deficit hyperactivity disorder (ADHD) Intolerance to at least a three month recent trial of an immediate release clonidine formulation. If the above conditions are met, the request will be approved for 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS For the treatment of attention deficit hyperactivity disorder (ADHD) in children as monotherapy and as adjunctive therapy to stimulant medications. DOSAGE AND ADMINISTRATION Initial Dose (Children 6 years of age and older): 0.1mg per day at bedtime Dosage Adjustment: Adjust in increments of 0.1 mg/day at weekly intervals until the desired response is achieved Maximum Dose: 0.4mg/day (0.2mg twice daily) REFERENCES 1. Kapvay. Prescribing Information. Shionogi Pharma Inc. June 2011. 2. Facts and Comparisons, St. Louis, 2013 efacts CliniSphere Version ISBN 1-57439-036-8. 3. Dobie C, Donald WB, Hanson M, Heim C, Huxsahl J, Karasov R, Kippes C, Neumann A, Spinner P, Staples T, Steiner L. Institute for Clinical Systems Improvement. Diagnosis and Management of Attention Deficit Hyperactivity Disorder in Primary Care for School-Age Children and Adolescents. http://bit.ly/adhd0312. Updated March 2012. 4. Custer JW, Rau RE, eds. The Harriet Lane Handbook: A Manual for Pediatric House Officers. The Harriet Lane Service, Children's Medical and Surgical Center of the Johns Hopkins Hospital. 18th ed. Philadelphia, PA: Mosby/Elsevier; 2009. Revision/Review Date: 2/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA KUVAN (sapropterin dihydrochloride): Tablets: 100mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR INITIAL AUTHORIZATION: Documentation of a confirmed diagnosis of Phenylketonuria (PKU) Documentation of the patient s baseline blood Phe level.(request from within 30 days of the request) Documentation consistent with order forms OR receipts (from no more than 30 days prior to the request) that the patient is currently utilizing a Phe restricted diet with Phe-free medical products/foods.(see examples in Table 1) Documentation of the patient s current weight. The medication is being prescribed at a dose no greater than the FDA approved maximum initial dose of 10 mg/kg/day. If the above conditions are met, the request will be approved for a duration of 1 month; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR 1 st REAUTHORIZATION: Documentation of the patient s current weight. Documentation consistent with current order forms OR receipts that the patient is currently utilizing a Phe restricted diet with Phe-free medical products/foods. (see examples in Table 1) Documentation of at least two separate blood Phe level results. For patients who require an increase in their daily dose (up to the FDA approved maximum of 20 mg/kg/day) due to a lack of a response then documentation must be submitted that the patient s blood Phe level DID NOT decrease at least 20% from baseline. Note: for patients who did response to treatment and obtained a 20 % of more reduction in their blood Phe level after one month of treatment, the subsequent prescribed dosage may fall anywhere within the approved FDA dosage range. The medication is being prescribed at an FDA approved dosage. If the above conditions are met, the request will be approved for a duration of 1 month for patients who require a dose increase to 20 mg/kg/day due to nonresponsiveness and for all other patients the request will be approved for a duration of 3 months; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR 2 nd REAUTHORIZATION AND THEREAFTER: Documentation of the patient s current weight. Documentation consistent with current order forms OR receipts (from no more than 30 days prior to the request) that the patient is currently utilizing a Phe restricted diet with Phe-free medical products/foods. (see examples in Table 1) For patients who required an increase in dosage to 20 mg/kg/day due to a lack of response to the initial dose then documentation of the patients blood Phe level results (results taken after the patient s dosage was increased). For these patients, if their decrease in blood Phe level was < 20% from baseline, then they will be classified as a non-responder and NO further authorization for this medication will be given. OR For all other patients, then documentation of the patients blood Phe levels (results from at least 30 days prior to the request). The medication is being prescribed at an FDA approved dosage. If the above conditions are met, the request will be approved for a duration of 4 months; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION:

The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or the standard of care guidelines. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6-month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the standard of care guidelines. Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication If all of the above conditions are met, the request will be approved for up to a 6-month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical FDA APPROVED INDICATIONS: Kuvan is indicated to reduce blood phenyalanine (Phe) levels in patients with hyperphenylalaniemia (HPA) due to tetrahydrobiopterin-(bh4-) responsive Phenylketonuria (PKU). Kuvan is to be used in conjunction with a Phe-restricted diet. DOSAGE AND ADMINISTRATION: The recommended starting dose of Kuvan is 10 mg/kg/day taken once daily. Kuvan should be taken orally with food to increase the absorption. Kuvan tablets should be dissolved in 4 to 8 oz. (120-240 ml) of water or apple juice and taken within 15 minutes. DOSAGE ADJUSTMENTS: Response to therapy is determined by change in blood Phe following treatment with Kuvan at 10 mg/kg/day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Kuvan treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day. Patients whose blood Phe does not ecrease after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment with Kuvan should be discontinued in these patients. Once responsiveness to Kuvan has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. DETERMINIATION OF PATIENTS DOSE: The number of Kuvan tablets that a patient should take per day is rounded up for any dose ending in 50-99mg and rounded down for a dose ending in 1-49 mg. Please see table below for examples: Patient s Weight Starting dose Maintenance Dose

(in kg) (10 mg/kg/day) 10 mg/kg/day 20 mg/kg/ day 13.6 136 mg (1 tablet per day) 136 (1 tablet per day) 272 (3 tablets per day) 40.2 402 mg (4 tablets per day) 402 (4 tablets per day) 804 (8 tablets per day) 52.8 528 mg (5 tablets per day) 528 (5 tablets per day) 1056 mg (11 tablets per day) DOSAGE ADJUSTMENTS: The response to therapy is determined by changes in blood Phe following treatment with Kuvan at 10 mg/kg/day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Kuvan treatment and periodically for up to a month. If blood Phe levels do not decrease from baseline at a dose of 10 mg/kg/day, the dose may then be increased to 20 mg/kg/day. For patients whose blood Phe levels do not decreases after 1 month of treatment at a dose of 20 mg/kg/day are then deemed to be non-responders and treatment with Kuvan should be discontinued in these patients. Doses of Kuvan may be adjusted in the range of 5 to 20 mg/kg taken once daily. Table 1 Example of Phenylalanine-Free Medical Products Phenyl-Free (phenylalanine free diet powder), Loplex, Periflex, Phlex-10, PKU 2, PKU 3, XPhe Maxamaid, XPhe Maxamum, REFERENCES: 1. Kuvan Prescribing Information, BioMarin Pharmaceutical Inc, 12/2007. 2. Levy HL, Milanowski A, Chakrapani A, et al. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomized placebo-controlled study. Lancet 2007; 370: 504-10. 3. Matalon R, Michals-Matalon K, Koch R, et al. Response of patients with phenylketonuria in the US to tetrahydrobiopterin. Molecular Genetics and Metabolism 2005; 86: S17-S21. 4. Michals-Matalon K, Bhatia G, Guttler F, et al. Response of Phenylketonuria to Tetrahydrobioperin. The Journal of Nutrition 2007; 137: 1564S-67S. 5. Burton BK, Grange DK, Milanowski A, et al. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicenter, open-label, screening study. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

KYTRIL (granisetron) Tablet: 1mg; Oral solution: 1mg/5ml FORMULARY STATUS: Non-Formulary (generic) TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PA CRITERIA FOR APPROVAL: Diagnosis of nausea and/or vomiting associated with emetogenic cancer chemotherapy or radiation therapy. AND Documented trial and failure with maximum therapeutic doses or intolerance to ondansetron. If the above condition is met, the request will be approved with a quantity limit of 12 tablets/30 days or 60mL/30 days for the duration of the chemotherapy or radiation, not to exceed 3 months; if the above condition is not met, the request will be referred to a Medical Director for medical necessity review. Quantities Greater than 12 tablets/30 days or 60ml/30days after meeting Non Formulary Medication Criteria: If the patient requires doses greater than 12 tablets/30days or 60ml/30 days the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Antiemetic: Prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation. DOSAGE AND ADMINISTRATION: Emetogenic Chemotherapy: Adults: The recommended adult dosage of Kytril is 2mg once daily or 1mg twice daily. In the 2mg once daily regimen, two 1mg tablets or 10mL of Kytril Oral Solution (2 teaspoonfuls, equivalent to 2mg of Kytril) are given up to 1 hour before chemotherapy. In the 1mg twice daily regimen, the first 1mg tablet or one teaspoonful (5mL) of Kytril Oral Solution is given up to 1 hour before chemotherapy, and the second table or second teaspoonful (5mL) of Kytril Oral Solution, 12 hours after the first. Either regimen is administered only on the day(s) chemotherapy is given. Continued treatment, while not on chemotherapy, has not been found useful. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Radiation (Either Total Body Irradiation or Fractionated Abdominal Radiation): Adults: The recommended adult dosage of oral Kytril is 2mg once daily. Two 1mg tablets or 10mL of Kytril Oral Solution (2 teaspoonfuls, equivalent to 2 mg of Kytril) are taken within 1 hour of radiation. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. REFERENCES: 1. Kytril. Prescribing Information. Roche Laboratories, Inc. March 2010. 2. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 3. The National Comprehensive Cancer Network (NCCN) and The American Cancer Society (ACS). Nausea and Vomiting. Treatment Guidelines for Patients with Cancer. Version 1. January 2001. 4. Steiner M, Yorgason RZ, Vermeulen LC, Theisen J. Patient outcomes after therapeutic interchange of dolasteron for granisetron. Am J Health-Syst Pharm. 2003;60(10):1023-8. 5. Markman M. Progress in preventing chemotherapy-induced nausea and vomiting. Cleve Clin J Med. 2002 Aug;69(8):609-17. 6. Lanciano R, Sherman DM, Michalski J, Preston AJ, Yocom K, Friedman C. The efficacy and safety of once-daily Kytril (granisetron) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy. Cancer Invest. 2001;19(8):763-72. 7. Tan M. Granisetron: new insights into its use for the treatment of chemotherapy induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sept;4(9):1563-71. 8. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Antiemesis. Version 4. 2009. Available at: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA LESCOL (fluvastatin) Capsule: 20mg, 40mg LESCOL XL (fluvastatin extended-release) Tablet: 80mg FORMULARY STATUS: Formulary FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Documented treatment history of trial and failure or intolerance to at least one of the following medications: Atorvastatin, simvastatin, pravastatin, or lovastatin. If the above conditions are met, the request will be approved within appropriate dosing with 12-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATION: In addition to a diet restricted in saturated fat and cholesterol, Lescol(fluvastatin) & LescolXL (fluvastatin extended-release) are approved for the following: Hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia Heterozygous familial hypercholesterolemia in pediatric patients Secondary prevention of coronary events Coronary atherosclerosis DOSAGE AND ADMINISTRATION: Reduction of LDL-C goal > 25% Starting dose is 40mg in the evening, 80mg as one Lescol XL tablet as a single dose at any time of the day,or 80mg in divided doses of the 40mg capsule given twice daily. Dose adjustments made according to the patient s response to therapy and established treatment guidelines. Reduction of LDL-C goal < 25% Starting dose is 20mg daily. Heterozygous Familial Hypercholesterolemia in Pediatric Patients Starting dose is 20mg day. Dose adjustments up to a maximum daily dose of 40mg twice daily or 80mg (Lescol XL) once daily should be done at 6 week intervals. Doses should be individualized according to the goal therapy. Concomitant Lipid-Lowering Therapies: Use with fibrates and niacin products may increase risk of myopathy/rhabdomyolysis. Do not break, crush or chew Lescol XL tablets or open Lescol capsules prior to administration. REFERENCES: 1. Lescol/Lescol XL Product Information. Novartis Pharmaceuticals Corporation. July 2011. 2. Facts and Comparisons, St. Louis, efacts 2011 CliniSphere Version ISBN 1-57439-036-8. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA LIDODERM (lidocaine) Patch: 5% FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of postherpetic neuralgia AND Documented trial and failure or intolerance to the following medications: amitriptyline or nortriptyline and gabapentin If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: For relief of pain associated with post herpetic neuralgia DOSAGE AND ADMINISTRATION: Apply Lidoderm patch to intact skin to cover the most painful area. Apply up to three patches, only once for up to 12 hours within a 24 hour period. REFERENCES: 1. Attal N, et al. EFNS Guidelines on Pharmacological Treatment of Neuropathic Pain. European Journal of Neurology. 2006;13: 1153-1169. 2. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 3. Dubinsky RM, et al. Practice Parameter: Treatment of Postherpetic Neuralgia: An Evidence-Based Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959-965. 4. Galluzzi KE. Management Strategies for Herpes Zoster and Postherpetic Neuralgia. J Am Osteopath Assoc. 2007 Mar;107(3 Suppl 1):S8-S13. 5. Lidoderm. Prescribing Information. Endo Pharmaceuticals, Inc. February 2008. 6. Lidoderm Data on File. Endo Pharmaceuticals, Inc. March 2010. 7. Neurontin. Prescribing Information. Parke-Davis, Divison of Pfizer, Inc. January 2007. 8. Rowbotham, Michael, et al. Gabapentin for the Treatment of Postherpetic Neuralgia. JAMA. 2 December 1998. Vol. 280, No. 21: 1837-1842. 9. Watson, CPN, et al. Nortriptyline Versus Amitriptyline in Postherpetic Neuralgia. Neurology. 1998; 51: 1166-1171. 10.Dworkin, Robert et al. Pharmacologic Management of Neuropathic Pain: Evidence-based Recommendations. Pain. 2007 Dec 5;132(3):225-6 Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Risperdal Consta (risperidone): 12.5 mg/2ml, 25 mg/2ml, 37.5 mg/2ml, 50 mg/2ml syringes Invega Sustenna (paliperidone palmitate): 38 mg, 78 mg, 117 mg, 156 mg, 234 mg syringes Zyprexa Relprevv (olanzapine): 210mg, 300mg, 405mg vials Abilify Maintena (aripiprazole): 300mg, 400mg vials PA CRITERIA FOR INITIAL AUTHORIZATION: PA Criteria for Initial Authorization 1. The member has a long-term history (>3 months) of oral anti-psychotic medication noncompliance AND documentation submitted indicates that the member had significant clinical decompensation or there is a high risk for decompensation and functional impairment (e.g. hospitalizations, safety risk) AND documentation of a drug adherence treatment plan was also submitted that indicates the member failed the following types of measures to improve compliance with a preferred oral medications and/or a reason for why any of the following measures were not implemented to improve compliance with a preferred oral medications as clinically applicable: Psychosocial interventions Psychoeducational interventions that have a behavioral component and supportive services. Provided member with concrete instructions and problem-solving strategies (i.e. reminders, self-monitoring tools, cues, and reinforcements). And/OR the member has a documented medical reason (i.e. documented treatment failure to maximum doses and/or has Intolerable side effects or drug interactions) for not using a preferred atypical antipsychotic medication. 2. Documentation submitted indicates that the medication is being prescribed for an FDA approved indication. 3. The patients has documentation submitted (consistent with pharmacy claims data) of a history of receiving oral risperidone (Risperdal ), paliperidone (Invega ), olanzapine (Zyprexa ) and/or aripiprazole (Abilify ) daily without any clinically significant side effects. If all of the above conditions are met, the request will be approved with a 16-week duration; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR REAUTHORIZATION: 1. Documentation submitted indicates that the medication continues to be prescribed for its FDA approved indication. 2. Documentation submitted indicating how the member clinically improved or stabilized while receiving the medication. 3. Documentation submitted indicates that the member is tolerating medication. If all of the above conditions are met, the request will be approved with a 16-week duration, however for patients stable on a dose (e.g. > 6 months) can be approved for a 12 month duration. if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. FDA APPROVED INDICATIONS: Risperdal Consta is indicated: For the treatment of schizophrenia. As monotherapy or as adjunctive therapy to lithium or valprate for the maintenance treatment of Bipolar I Disorder

Invega Sustenna is indicated for: The acute and maintenance treatment of schizophrenia in adults Zyprexa Relprevv is indicated for: The treatment of schizophrenia Abilify Maintena is indicated for: Acute treatment of schizophrenia DOSAGE AND ADMINISTRATION Risperdal Consta: Risperdal Consta should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. The recommended dose is 25mg IM every 2 weeks. Some members not responding to 25mg may benefit from a higher dose of 37.5mg or 50mg. The maximum dose should not exceed 50mg of Risperdal Consta every 2 weeks. No additional benefit was observed with dosages greater than 50mg of Risperdal Consta, however, a higher incidence of adverse effects was observed. A lower dose of 12.5mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentration, or in patients who have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5mg dose has not been investigated in clinical trails. Oral Risperdal (or another anti-psychotic medication) should be given with the first injection of Risperdal Consta and continued for 3 weeks (and then discontinued) to ensure that adequate therapeutic plasma concentrations are maintained. Based on FDA labeling, an upward dosage adjustment should not be made more frequently than every 4 weeks. The clinical effects of a dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose. However, because it may take up to 8 weeks for the medication to reach steady state, and based on Texas Implementation of Medical Algorithms (TIMA) which recommends to evaluate a response to a dose of an anti-psychotic medication after a member has been on therapy for about 4 weeks, the anticipated full therapeutic effects for a given dose of Risperdal Consta may not occur until the member has received at least 12 weeks of therapy. Do not combine two different dosage strengths of Risperdal Consta in a single administration. Invega Sustenna: Recommended starting dose of Invega Sustenna is a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. The recommended monthly maintenance dose is 117 mg; some patients my benefit from lower or higher maintenance doses within the recommended range of 39 to 234 mg based on individual patient tolerability and/or efficacy.

Table1. Doses of Invega and Invega Sustenna needed to attain similar paliperidone exposure at steady-state Formulation Invega Invega Sustenna Dosing Frequency Dose (mg) Once Daily 12 6 3 Once every 4 weeks 234 117 39-78 Zyprexa Relprevv: Zyprexa Relprevv is intended for deep intramuscular gluteal injection only and should not be administered intravenously or subcutaneously. Table2. Recommended Dosing for Zyprexa Relprevv based on Correspondence to Oral Zyprexa Doses Target Oral Zyprexa Dose 10 mg/day 15 mg/day 20 mg/day Dose of Zyprexa Relprevv During the First 8 weeks 210 mg/2 weeks or 405/4 weeks 300 mg/2 weeks 300 mg/2 weeks Maintenance Dose After 8 weeks of Zyprexa Relprevv Treatment 150 mg/2 weeks or 300 mg/4 weeks 210 mg/2 weeks or 405 mg/4 weeks 300 mg/2 weeks Abilify Maintena: Abilify injection is intended only to be administered by intramuscular injection in the gluteal muscle by a health care professional Recommended starting dose and maintenance dose is 400mg administered monthly as a singly injection In conjunction with the first dose, patients should take 14 consecutive days of concurrent oral aripiprazole (10 to 20mg) or current oral antipsychotic DOSAGE ADJUSTMENTS: Risperdal Consta Members with hepatic or renal impairment should be treated with titrated doses of oral Risperdal prior to initiating treatment with Risperdal Consta. The recommended starting dose is 0.5mg oral Risperdal bid during the first week, which can be increased to 1mg bid or 2mg once daily during the second week. If a dose of at least 2mg oral Risperdal is well tolerated, an injection of 25mg Risperdal Consta can be administered every 2 weeks. Alternatively, a starting dose of

Risperdal Consta of 12.5mg may be appropriate. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection has begun. Invega Sustenna For patients with mild renal impairment (CrCl > 50 ml/min to < 80 ml/min), recommended starting treatment with a dose of 156 mg on treatment day 1 and 117 mg one week later, both administered in the deltoid muscle. Thereafter, follow with monthly injections of 78 mg in either the deltoid of gluteal muscle. Invega Sustenna is not recommended in patient with moderate or severe renal impairment. (CrCl < 50 ml/min). Invega Sustenna For patients with mild renal impairment (CrCl > 50 ml/min to < 80 ml/min), recommended starting treatment with a dose of 156 mg on treatment day 1 and 117 mg one week later, both administered in the deltoid muscle. Thereafter, follow with monthly injections of 78 mg in either the deltoid of gluteal muscle. Invega Sustenna is not recommended in patient with moderate or severe renal impairment. (CrCl < 50 ml/min). Abilify Maintena If there are adverse reactions with the 400mg dosage, dose reduction to 300mg once monthly is recommended. Dose adjustments are required for missed doses. Additional dosage adjustment should be made for patients who are CYP2D6 poor metabolizer and for patients taking CYP2D6 inhibitors, CYP3A4 inhibitors or CYP3A4 inducers for greater than 14 days. CYP2D6 Poor Metabolizers Adjusted Dose CYP2D6 Poor Metabolizers CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors 300mg 200mg Patients Taking 400mg of ABILITY MAINTENA Strong CYP2D6 or CYP3A4 inhibitors Strong CYP2D6 and CYP3A4 inhibitors CYP3A4 inducers 300mg 200mg Avoid use Patients Taking 300mg of ABILIFY MAINTENA Strong CYP2D6 or CYP3A4 inhibitors CYP2D6 and CYP3A4 inhibitors CYP3A4 inducers 200mg 160mg Avoid use

SWITCHING FROM OTHER ANTI-PSYCHOTICS: There are no systemically collected data to specifically address switching schizophrenic members from other antipsychotics to either Risperdal Consta or Invega Sustenna, or concerning concomitant administration with other antipsychotics. Risperdal Consta: Oral Risperdal (or another anti-psychotic medication) should be given with the first injection of Risperdal Consta and should be continued for 3 weeks after the first injection of Risperdal Consta to ensure that therapeutic concentrations are maintained until the main release phase of risperidone from the injection site has begun. For schizophrenic members who have never taken oral Risperdal, it is recommended to establish tolerability with oral Risperdal prior to initiating treatment with Risperdal Consta. Invega Sustenna: For patients who have never taken oral paliperidone or oral or injectable risperirone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with Invega Sustenna. Previous oral antipsychotics can be discontinued at the time of initaion of treatment with Invega Sustenna. Patients previously stabilized on different doses of Invega Extended-Release tablets can attain similar paliperidone steady-state exposure during maintenance treatment with Invega Sustenna. Zyprexa Relprevv: There are no systematically collected data to specifically address how to switch patients with schizophrenia from other antipsychotics to Zyprexa Relprevv. Abilify: For patients naïve to aripiprazole, establish tolerability with oral ariopirazole prior to initiating ABILIFY MAINTENA. In conjunction with the first does, the patients should take 14 consecutive days of concurrent oral aripiprazole (10 to 20mg) or current oral antipsychotic. References 1. Miller Alexander L, Hall Catherine S, et al. Texas Implementation of Medical Algorithms; Schizophrenia Module. Jan. 2003. Available from Internet: TIMA Schizophrenia Module http://www.mhmr.state.tx.us/centraloffice/medicaldirector/timascz1algo.pdf 2. Risperdal Constar Package Insert. Ortho-McNeil-Janseen Pharmaceuticals, Inc. December 2012. 3. Invega Sustenna Package Insert. Ortho-McNeil-Janseen Pharmaceuticals, Inc. September 2011. 4. Swainston Harrison T, Goa KL. Long-acting risperidone: a review of its use in schizophrenia. CNS Drugs, 18(2): 113-32, 2004. 5. Zyprexa Relprevv Package Insert. Eli Lilly and Company. July 2011. 6. Abilify Maintena Package Insert. Otsuka Pharmaceutical Co, Ltd. February 2013. Revision/Review Date: 04/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FOR LOW MOLECULAR WEIGHT HEPARIN (LMWH) THERAPY Arixtra (fondaparinux): 2.5mg/0.5ml, 5mg/0.4ml, 7.5mg/0.6ml and 10mg/0.8ml pre-filled syringes Fragmin (dalteparin): 2,500U/ml, 5,000U/ml, 7,500U/ml, 10,000U/ml, 12,500U/ml, 15,000U/ml 18,000U/ml (prefilled syringes) and 95,000U multi-dose vials Lovenox (enoxaparin): 30mg/0.3ml, 40mg/0.4ml, 60mg/0.6ml, 80mg/0.8ml, 100mg/ml, 120mg/0.8ml, 150mg/ml (pre-filled syringes) and 300mg/3ml multi-dose vials Formulary Status: Non-formulary. Treatment durations longer than 10 days will require prior authorization. Treatment durations of 10 days or less will automatically process at the point of sale. PA CRITERIA FOR APPROVAL FOR USE IN DEEP VEIN THROMBOSIS (DVT) AND/OR PULMONARY EMBOLIS (PE): The medication is being prescribed for the prevention and/or treatment of a DVT and/or PE. Documentation of the patient s current weight. The medication is being prescribed at a dose that is within FDA approved guidelines. If the request is for a duration of therapy greater than 31 days then a letter of medical necessity that provides a valid medical reason why the member cannot be treated with Coumadin or Heparin for long-term therapy (>31 days) must be submitted. If all of the above conditions are met, the request will be approved for up to a 31-day duration (unless greater duration of therapy is requested and medically necessary then will be approved for up to a 6 month duration); if all of the above criteria are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR USE IN A PREGNANT MEMBER: The medication is being prescribed for the prevention and/or treatment of a DVT and/or PE while the member is pregnant. Documentation of the patient s current weight and expected due date (EDD). If the request is to continue LMWH treatment postpartum then documentation of the patient s actual or expected due date and current weight is required AND THEN up to 6 weeks of additional treatment may be authorized. The medication is being recommended and prescribed by an obstetrician or a hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6 month duration (or up until the patient s expected due date, whichever comes first); if all of the above criteria are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL FOR USE IN MEMBER WITH CANCER: The medication is being prescribed for the prevention and/or treatment of a venous thromboembolism (VTE) (a proximal DVT and/or PE) for a member with cancer. Documentation of the patient s current weight. The medication is being recommended and prescribed by an oncologist/hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met, the request will be referred to a Medical Director for medical necessity review. REAUTHORIZATION CRITERIA FOR APPROVAL FOR USE IN MEMBER WITH CANCER BEYOND SIX MONTHS: The medication is being for the prevention and/or treatment of a VTE for a member with cancer. Documentation of the patient s current weight. If the request for a duration of therapy greater than 6 months then a letter of medical necessity that provides a valid medical reason why the member needs to continue treatment and cannot be treated with Coumadin for long-term therapy. The medication is being recommended and prescribed by an oncologist/hematologist at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 6 month duration; if all of the above criteria are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATION: Arixtra:

Indicated for the prophylaxis of DVT, which may lead to PE, for: o Patients undergoing hip fracture surgery, including extended prophylaxis. o Patients undergoing hip or knee replacement surgery. o Patients undergoing abdominal surgery who are at risk for thromboembolic complications. Indicated for the treatment of: o Of acute DVT when administered in conjunction with warfarin sodium. o Of acute PE when administered in conjunction with warfarin sodium when the initial therapy is administered in the hospital. Fragmin: Indicated for the prophylaxis of DVT, which may lead to PE, for: o Patients undergoing hip replacement surgery. o Patients undergoing abdominal surgery who are at risk for thromboembolic complications. o Patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness. Indicated for the prophylaxis of ischemic complications in unstable angina and non-q-wave MI when concurrently administered with aspirin therapy. Indicated for the extended treatment of symptomatic VTE (a proximal DVT and/or PE) to reduce the recurrence of VTE in patients with cancer. Innohep: Indicated for the treatment of acute symptomatic DVT, with or without PE, when administered in conjunction with warfarin. Lovenox: Indicated for the prophylaxis of DVT, which may lead to PE, in: o patients undergoing abdominal surgery who are at risk for thromboembolic complications. o patients undergoing hip replacement surgery, during and following hospitalization o patients undergoing knee replacement surgery o in medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness. Indicated for the treatment of acute DVT for inpatient treatment with or without PE and outpatient treatment without PE. Indicated for the prophylaxis of ischemic complications of unstable angina and non-q-wave myocardial infarction (MI). Indicated for the treatment of acute segment elevation myocardial infarction (STEMI) in patients. DOSAGE AND ADMINISTRATION: Arixtra: o DVT/PE Treatment: the recommended dose is 5mg (for patients weighing less then 50kg), 7.5mg (for patient weighing between 50-100kg) or 10mg (for patients weighing more than 100kg) by SQ injection once daily. Treatment should continue for at least 5 days and until a therapeutic oral anticoagulant effect is established (INR 2.0 to 3.0). The usual duration of therapy is 5-9 days, however up to 26 days of treatment has been used. o DVT Prophylaxis Following Abdominal Surgery: the recommended dose is 2.5mg first administered 6-8 hours after surgery, then daily. The usual duration of therapy is 5-9 days, however up to 10 days have been used. o DVT Prophylaxis Following Hip Fracture or Hip/Knee Replacement Surgery: following hip fracture repair, hip replacement, or knee replacement the recommended dose is 2.5mg SQ daily. The usual duration is 5-9 days however up to 11 days administration has been tolerated. For hip fracture repair surgery patients up to 24 days of treatment is recommended. Fragmin: o DVT Prophylaxis: Abdominal or hip replacement surgery: 2500-5000 IU SQ daily for 1 day pre-op followed by 5-10 days of the same dose range. o DVT/PE Treatment: the recommended dose is 200 IU/kg SQ daily. The maximum recommended dose is 18,000 Units daily. o Unstable angina/non-q-wave MI: the recommended dose is 120 IU/kg SQ every 12 hours in conjunction with low-dose oral aspirin therapy. The maximum recommended dose is 10,000 IU per 12 hours. The usual duration of therapy is 5 to 8 days. o Cancer related Venous Thromboembolism: the recommended dose for the first 30 days is 200 IU/kg SQ daily (dose not to exceed 18,000 IU daily), then for months 2-6 the recommended dose is 150 IU/kg SQ daily (not to exceed 18,000 IU daily). Dosing beyond 6 months has not been established. o For use in Pregnancy: for acute treatments of VTE dose based upon the manufacturer s recommendations and adjust for weight gain as the pregnancy progresses. A goal anti-factor Xa level is 0.5 to 1.2 U/ml. For prophylaxis of VTE a dose of 5000-7500 IU SC once daily dose adjusted to a peak anti-factor Xa level of 0.2 to 0.6U/mL. Lovenox: o DVT Prophylaxis: for hip or knee replacement surgery the recommended dose is 30mg SC every 12 hours, up to 14 days. For hip replacement surgery 40mg SC once daily may be considered. Treatment is recommended to continue for 21 days. o Abdominal surgery: the recommended dose is 40mg SC once daily. The usually duration of administration is 7 to 10 days, however up to 12 days of treatment has been administered in clinical trials. o DVT/PE Treatment: In patients who can be treatment at home the recommended dose is 1 mg/kg SC every SC or 1.5 mg/kg once a day SC. Treatment could continue for a minimum of 5 days and until a therapeutic 1 oral anticoagulant effect has been achieved (INR between 2.0-3.0). The average duration of administration is 7 days, however up to 17 days has been administered

in controlled clinical trials. o Unstable angina/non-q-wave Myocardial Infarction (MI): the recommended dose is 1 mg/kg SC every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily). The usual duration of therapy is 2 to 8 days, however up to 12.5 days of treatment has been administered in clinical trials. o Medical patients during acute illness: the recommended dose is 40 mg once daily SC. The usual duration of administration is 6 to 11 days, however up to 14 days has been administered in controlled clinical trials. o Treatment of acute ST-segment Elevation MI: the recommended dose is a single IV bolus of 30 mg plus a 1 mg/kg SC dose followed by 1 mg/kg administered SC every 12 hours (maximum 100 mg for the first doses only, followed by 1 mg/kg dosing for the remaining doses). o Pregnancy: For acute treatment of VTE, dose based upon the manufacturer s recommendations and should be adjusted for weight gain as the pregnancy progresses. A goal anti-factor Xa level is 0.5 to 1.2 U/mL. For prophylaxis of VTE a dose of 40mg SC once daily dose adjusted to a peak anti-factor Xa level of 0.2 to 0.6U. DOSAGE ADJUSTMENTS: Arixtra: o The use of Arixtra is contraindicated in patients with severe renal impairment (creatinine clearance of < 30ml/minute) o The use of Arixtra is contraindicated in patients who weigh less than 50 kg when used for prophylactic therapy in hip fracture, hip or knee replacement surgery, or abdominal surgery. Fragmin: o When used in cancer patient with symptomatic VTE: If the patient s platelet count is between 50,000-100,000/mm 3 the dose of Fragmin should be reduced by 2,500 IU until their platelet count recovers to > 100,000/mm 3. If the patient s platelet count is < 50,000/mm 3 Fragmin should be discontinued until their platelet count is > 50,000/mm 3. o When used in cancer patient with symptomatic VTE: with renal impairment (creatinine clearance < 30 ml/minute). Patients should have their anti-xa levels monitored to determine the appropriate dose of Fragmin. The target level for the anti-xa is 0.5-1.5 IU/ml. When a patient s anti-xa level the sampling should be done 4-6 hours after the Fragmin dose and only after the patient has received 3-4 doses of Fragmin. Lovenox: Dosage Regimens for Patients with Severe Renal Impairment (Creatinine Clearance < 30ml/minute) Dosage Regimen 30 mg administered SQ once daily Indications Prophylaxis in abdominal, hip or knee replacement surgery Prophylaxis in medical patients during acute illness Inpatient treatment of acute DVT with or without PE, when given with warfarin Outpatient treatment of acute DVT without PE, when given with warfarin Prophylaxis of ischemic complications of unstable angina and non-q-wave MI, when given with aspirin Treatment of acute ST-STEMI in patients < 75 years old Treatment of acute ST-STEMI in patients >75 years old 30 mg administered SQ once daily 1 mg/kg administered SQ once daily 1 mg/kg administered SQ once daily 1 mg/kg administered SQ once daily 30mg single IV bolus plus a 1 mg/kg SQ dose followed by 1 mg/kg administered SQ once daily 1 mg/kg administered SQ once daily (no initial bolus) o Geriatric patients with acute ST-STEMI: for patients > 75 years old, do not given an initial bolus of Lovenox. Initiate dosing at 0.75 mg/kg SQ every 12 hours (maximum dose of 75 mg for the first two doses only) followed by 0.75 mg/kg SQ dosing for the remaining doses. WARNING: When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients who are anticoagulated or scheduled to be anticoagulated with low molecular weight heparins (LMWHs) or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma that can result in long-term or permanent paralysis. The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. Frequently monitor patients for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. The physician should consider the potential benefit vs. risk before neuraxial intervention in patients anticoagulated or scheduled to be anticoagulated for thromboprophylaxis. REFERENCES: 1. NCCN Clinical Practice Guidelines in Oncology : Venous Thromboembolic Disease; V.1.2010 Update. 2. Fragmin Prescribing Information. Pfizer Pharmaceutical, October 2010.

3. Arixtra Prescribing Information. GlaxoSmithKline Pharmaceutical, February 2011. 4. Lovenox Prescribing Information. Sanofi-Aventis, April 2011 5. James AH. Prevention and Management of Venous Thromboembolism in Pregnancy. The American Journal of Medicine 2007; 120 (10B): S26-34. 6. Ellison J, Walker ID and Greer IA. Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy. British Journal of Obstetrics and Gynaecology 2000; 107: 1116-21. 7. Lee AYY, Rickles FR, Julian JA, et al. Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients with Cancer and Venous Thromboembolism. Journal of Clinical Oncology 2005; 23(10): 2123-29. 8. Nishioka J, Goodin S. Low-molecular-weight heparin in Cancer-Associated Thrombosis: Treatment, Secondary Prevention, and Survival. Journal of Oncology Pharmacy Practice 2007: 13: 85-97. 9. American College of Chest Physicians : Antithrombotic Therapy for Venous Thromboembolic Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. 2004; 126(3): 401S-28S. 10. American College of Chest Physicians: Prevention of Venous Thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. 2004; 126(3): 338s-400s. 11. Duplaga BA, Rivers CW and Nutescu E. Dosing and Monitoring of Low-Molecular-Weight Heparins in Special Populations. Pharmacotherapy 2001; 21(2): 318-34. 12. Yusuf S, Mehta S, Afzal Rizwan, et al. Effects of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST- Segment Elevation Myocardial Infarction: The OASIS-6 Randomized Trial. JAMA 2006; 295: 1519-30. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician review must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA MEPRON (atovaquone) Suspension: 750mg/5ml FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Diagnosis of Pneumocystis carinii pneumonia (PCP) or diagnosis with the need to prevent PCP infection. AND Documented trial and failure with therapeutic doses or intolerance to trimethoprimsulfamethoxazole (TMP-SMX) (first line therapy). If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: 1. Pneumocystis carinii pneumonia: Prevention of PCP in patients who are intolerant to trimethoprimsulfamethoxazole (TMP-SMX). 2. Acute oral treatment of mild-to-moderate PCP in patients who are intolerant to trimethoprimsulfamethoxazole (TMP-SMX). DOSAGE AND ADMINISTRATION: 1. Prevention of PCP: Adults and adolescents 13 to 16 years of age: 1500 mg (10ml) once daily with a meal. 2. Treatment of mild-to-moderate PCP: Adults and adolescents 13 to 16 years of age: 750 mg (5ml) administered with food twice daily for 21 days (total daily dose 1500 mg). REFERENCES: 1. Mepron. Prescribing Information. GlaxoSmithKline. May 2008. 2. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 3. Kovacs JA, Gill VJ, Meshnick S, Masur H. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001 Nov 21;286(19):2450-60 4. 2002 4. USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. U.S. Public Health Servic (USPHS) and Infection Diseases Society of America (IDSA) June 14, 2002 http://aidsinfo.nih.gov/contentfiles/oipreventiongl.pdf. 5. Treating Opportunistic Infections Among HIV Infected Adults and Adolescents. NIH/HIV Medicine Association/Infectious Diseases Society of America. December 17, 2004 http://aidsinfo.nih.gov/contentfiles/treatmentofoi_aa.pdf. 6. Rosenberg DM, McCarthy W, Slavinsky J, Chan CK, Montaner J, Braun J, Dohn MN, Caldwell PT. Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients. AIDS 2001 Jan 26;15(2):211-4 7. Chan C, Montaner J. Letabvre EA, et al. Atovaquone suspension compared with aerosolized pentamidine for prevention of pneumocystis carinii pneumonia in adult immunodeficiency virus-infected subjects intolerant to trimethoprim or sulfonamides. J Infect Dis. Aug 1999, 180(2):369-76. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA METANX Tablet (brand of L-methylfolate w/ B6,B12) NEURPATH-B Tablet (generic of L-methylfolate w/ B6,B12) FORMULARY STATUS: Non-Formulary FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Documentation of dietary management of endothelial dysfunction in patients with diabetic peripheral neuropathy. AND Trial and failure of or intolerance to therapeutic doses of amitriptyline or gabapentin. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. INDICATIONS: Metanx tablets are indicated for the distinct nutritional requirements of individuals under a physician s treatment for: Distinct nutritional requirements of patients with endothelial dysfunction who present with loss of protective sensation and neuropathic pain associated with diabetic peripheral neuropathy. Distinct nutritional requirements of patients with endothelial dysfunction and/or hyperhomocysteinemia who present with lower extremity ulceration(s). RECOMMENDED DOSAGE AND ADMINISTRATION: The recommended dose is one tablet twice daily (B.I.D.) or as directed by a physician. Metanx must be administered under a doctor's supervision and therefore is available by prescription only. WARNINGS AND PRECAUTIONS: Folates, when administered as a single agent in doses above 0.1mg daily, may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations remain progressive. REFERENCES: 1. Metanx. Prescribing Information. Pamlab, LLC. April 2010. 2. The Homocysteine Studies Collaboration: Homocysteine and Risk of Ischemic Heart Disease and Stroke. JAMA. 2002; 288(16):2015-22. 3. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in Vascular Disease. N Engl J Med. 2006;354:1567-77. 4. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006 Jun 29;354(26):2764-72. 5. Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E. Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial. Ann Intern Med. 2007 Jun 5;146(11):761-7. 6. Ambrosch A, Dierkes J, Lobmann R, Kühne W, König W, Luley C, et al. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabet Med. 2001 Mar;18(3):185-92. 7. Till U, Röhl P, Jentsch A, Till H, Müller A, Bellstedt K, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12. Atherosclerosis. 2005 Jul;181(1):131-5. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA MULTAQ (dronedarone) Tablet: 400 mg FORMULARY STATUS: Non-formulary PA CRITERIA FOR APPROVAL: 1. Diagnosis of paroxysmal or persistent arterial fibrillation (AF) or atrial flutter (AFL) with a recent episode. 2. Must not have NYHA Class IV heart failure or NYHA Class II-III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic 3. Request is from a cardiologist or electrophysiologist. 4. Must have at least one of the following associated risk factor(s): age > 70 hypertension diabetes prior cerebrovascular accident left atrial diameter 50 mm or left ventricular ejection fraction [LVEF] < 40%) If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: To reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent arterial fibrillation (AF) or atrial flutter (AFL) with a recent episode of AF/AFL and associated cardiovascular risk factors (i.e., age > 70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter 50 mm or left ventricular ejection fraction [LVEF] < 40%), who are in sinus rhythm or who will be cardioverted. DOSAGE AND ADMINISTRATION: Dose is 400 mg twice daily in adults. Multaq should be taken as one tablet with the morning meal and one tablet with the evening meal. Treatment with Class I or III antiarrhythmics (e.g., amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol) or drugs that are strong inhibitors of CYP3A (e.g., ketoconazole) must be stopped before starting Multaq REFERENCES: 1. Multaq Prescribing Information. Sanofi Aventis. July 2009. 2. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007 Sep 6;357(10):987-99. 3. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009 Feb 12;360(7):668-78. 4. Køber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008 Jun 19;358(25):2678-87. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FOR SELF INJECTABLE DISEASE MODIFYING IMMUNOMODULATORS FOR MULTIPLE SCLEROSIS (MS) Avonex (Interferon beta -1a): 30mcg kit (vial or pre-filled syringe) Betaseron (Interferon beta -1b): 0.3-mg pre-filled syringe Copaxone (Glatiramer Acetate) 20mg kit (pre-filled syringe) Extavia (Interferon beta -1b): 0.3-mg pre-filled syringe) Rebif (Interferon beta -1a): 8.8 mcg, 22mcg, 44 mcg pre-filled syringes PA CRITERIA FOR INITIAL APPROVAL: The member is an adult ( 18 y/o) member with relapsing/remitting MS (RRMS) or secondary progressive MS (SPMS) with a relapsing element. If the medication request is for Avonex, Betaseron, Extavia and/or any other Newly Marketed Self-Injectable Disease-Modifying Immunomodulating MS Agent, the member has a documented treatment failure to Copaxone and Rebif (see Box 1 in Glossary for definition of treatment failure) which is consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history, indicating they had received an adequate trial (including dates, doses of 6 months or more of each therapy) of Copaxone and Rebif and/or has another documented clinically significant medical reason (intolerance, hypersensitivity, contraindication, etc) for not taking Copaxone and Rebif for a minimum of 6 months each to treat their medical condition. The medication is being recommended and/or prescribed by a neurologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review REAUTHORIZATION CRITERIA: Documentation sent indicates that the member is an adult ( 18 y/o) and has one of the following types of MS: RRMS or SPMS with a relapsing element. Documentation indicating the member has clinically benefited from therapy. The medication was prescribed at an FDA approved dosage. Medication was recommended by a neurologist and/or prescribed by a neurologist. If all of the above conditions are met, the request will be approved for up to a 12-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review FDA INDICATIONS: Avonex is indicated for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Safety and efficacy in members with chronic progressive multiple sclerosis have not been evaluated. Betaseron is indicated for the treatment of relapsing forms of MS to reduce the frequency of clinical exacerabations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Copaxone is indicated for the reduction of the frequency of relapses in members with RRMS, including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Copaxone has NOT been formally evaluated in combination with interferon beta. Extavia is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Rebif is indicated for the treatment of relapsing forms of multiple sclerosis to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability. Efficacy in chronic progressive MS has not been established. DOSAGE AND ADMINISTRATION: Avonex: 30 micrograms intramuscularly once a week and sites for injection include thighs or upper arms. AVONEX may be titrated, starting with 7.5 micrograms for first week, to reduce flu-like symptoms. Increase dose by 7.5 micrograms each week for next 3 weeks until recommended dose of 30 micrograms Betaseron: 0.25 mg subcutaneously (SC) every other day. Start dose at 0.0625 mg (0.25 ml) SC every other day and titrate dose by increasing dose over six week period to 0.25mg (1.0mL) every other day.

Betaseron dosing titration schedule Recommended Titration Betaseron Dose Volume Weeks 1-2 25% 0.0625 mg 0.25 ml Weeks 3-4 50% 0.125 mg 0.50 ml Weeks 5-6 75% 0.1875 mg 0.75 ml Week 7+ 100% 0.25 mg 1.0 ml Copaxone: The recommended dose is 20 mg/day injected subcutaneously. Appropriate sites for injections include arms, abdomen, hips, and thighs. Extavia: 0.25 mg subcutaneously (SC) every other day. Start dose at 0.0625 mg (0.25 ml) SC every other day and titrate dose by increasing dose over six week period to 0.25mg (1mL) every other day. Extavia dosing titration schedule Recommended Titration Extavia Dose Volume Weeks 1-2 25% 0.0625 mg 0.25 ml Weeks 3-4 50% 0.125 mg 0.50 ml Weeks 5-6 75% 0.1875 mg 0.75 ml Week 7+ 100% 0.25 mg 1.0 ml Rebif: 22 mcg or 44 mcg injected SC 3 times weekly, if possible at the same time (in the late afternoon or evening) on the same 3 days at least 48 hours apart each week and to rotate SC injection sites. It is best to start members at 20% of prescribed dose 3 times/week and increase dose over a 4 week period to target dose. A titration pack containing 8.8 mcg and 22 mcg syringes is available for use during titration period. Rebif dosing titration schedule Recommended titration (% of final dose) Titration dose for Rebif 22 mcg Weeks 1-2 20% 4.4 mcg 8.8 mcg Weeks 3-4 50% 11 mcg 22 mcg Weeks 5+ 100% 22 mcg 44 mcg BOX 1: TREATMENT FAILURE: A member may be considered to have failed treatment if any of the following are documented: 8. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** 9. Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** 10. Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** 11. Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** Titration dose for Rebif 44 mcg 12. Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. ** 13. Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** 14. Members who have new or enlarging T2 lesions, increase in brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities.** ** These are members who have a documented treatment failure after receiving a minimum of 6 months each of Copaxone and Rebif. Diagnostic and/or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that the member has failed a minimum of 6 months of (Copaxone and Rebif) and/or has a documented medical reason (i.e. intolerance) for not utilizing each of these therapies for a minimum of 6 months.

Kurtzke Expanded Disability Status Scale (EDSS) Rating Status 0 Normal Neurological Exam 1.0 No Disability, minimal symptoms 1.5 No disability, minimal signs in more than one area 2.0 Slightly more disability in one area 2.5 Slightly greater disability in two areas 3.0 Moderate disability in one area but still walking independently 3.5 Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. REFERENCES: 1. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relapsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/prc.asp 2. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/prc.asp 3. Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004; 63(Suppl 6):S33-S40. 4. Lee MA. Smith L. Palace J. et al. Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis.? Brain.199; 122:1261-1270. 5. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006;245:111-116. 6. Brex P. Ciccarelli O. O Riordan J. et al. A longitudinal study of abnormalities on MRI and disability from MS. The New England Journal of Medicine.2002;246(3):158-164. 7. Miller DH. Grossman RI. Reingold SC. Et al The role of magnetic resonance techniques in understanding and managing MS. Brain.1998; 121:3-24. 8. Lycklama GJ. Van Walderveen MAA. Castelijns JA. Et al. Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain.1998; 121:687-697. 9. O Riordan JI. Thompson AJ. Kingsley DPE.et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain.1998; 121:495-503. 10. Rooney WD. Coyle PK. Recent advances in the neuroimaging of MS.Current Neurology and Neuroscience Reports.2005;5:217-224. 11. Polman CH, O'Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910. 12. Food and Drug Administration Homepage[ www.fda.gov]. Available from Internet. Accessed 2006 July 20.

13. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. 14. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006; 245:111-116. 15. Polman CH. Reingold SC. Edan G. et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the McDonald Criteria. Annals of Neurology.2005; 58:840-846. 16. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. 17. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. 18. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. 19. Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon β: implications for clinical trials. Annals of Neurology. 2002;52:400-406. 20. Rio J. Nos C. Tintore M. et al. Defining the response to interferon-β in RRMS patients. Annals of Neurology.2006;59:344-352. 21. Multiple Sclerosis International Federation. Available at: www.msif.org. 22. All about MS. Available at www.mult-sclerosis.org. 23. Avonex Prescribing Information. Biogen Idec, Inc. 02/2012. 24. Betaseron Prescribing Information. Berlex, Inc. 5/2010. 25. Copaxone Prescribing Information. TEVA Neurosciences. 02/2009. 26. Extavia Prescribing Information. Novartis Pharmaceuticals Corp. 03/2012. 27. Rebif Prescribing Information. Serono, Inc. 09/2011. 28. Rosalind C. Kalb, Ph.D., Director, Professional Resource Center, National Multiple Sclerosis Society, MS Guidelines 11 August 2004, personal email (11 August, 2004). 29. Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology, Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 58(2):169-178, January 22, 2002. 30. Morrow T, Brown J, Smith C, Thrower B. Considerations for the treatment of multiple sclerosis in the managed care setting. Formulary 2003; 38 (11). Revision/Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA NON-FORMULARY MEDICATION FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Appropriate diagnosis/indication for requested non-formulary medication AND Appropriate dose of medication based on age (i.e. pediatric and elderly populations) and indication AND Documented trial and failure or intolerance with up to three formulary medications used to treat the documented diagnosis. For medications where there is only one formulary agent, only that agent must have been ineffective or not tolerated OR No other formulary medication has a medically accepted use for the patient s specific diagnosis as referenced in the medical compendia*. OR All other formulary medications are contraindicated based on the patient s diagnosis, other medical conditions, or other medication therapy. If the above conditions are met, the request will be approved with up to a 6 month duration depending upon the diagnosis and usual treatment therapies; if the above conditions are not met, the request will be referred to a Medical Director (or Psychiatrist when applicable) for medical necessity review. *Medical compendia consists of the following: the Food and Drug Administration (FDA) approved indication(s) (Drug Package Insert), Micromedex, American Hospital Formulary Service (AHFS), DrugPoints (formerly known as USPDI). Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Psychiatrist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA OPHTHALMIC ANTIHISTAMINES STATUS Formulary, Pays at Point-of-Sale (First Line) ALAWAY OTC (ketotifen) Ophthalmic Solution: 0.025% (10mL) KETOTIFEN OTC (generic) Ophthalmic Solution: 0.025% (5mL) ZADITOR OTC (ketotifen) Ophthalmic Solution: 0.025% (5mL) ZYRTEC ITCHY EYE OTC (ketotifen) Ophthalmic Solution: 0.025% (5mL) STATUS Formulary, Requires Step Therapy (Second Line) PATADAY (olopatadine) Ophthalmic Solution: 0.2% (2.5mL) NOTE: Patient must meet #1 criterion for approval of Step Therapy request. STATUS Non-Formulary, Requires Prior Authorization (Third Line) BEPREVE (bepotastine besilate) Ophthalmic Solution: 1.5% (10mL) ELESTAT (epinastine) Ophthalmic Solution: 0.05% (5mL) EMADINE (emedastine) Ophthalmic Solution: 0.05% (5mL) OPTIVAR (azelastine) Ophthalmic Solution: 0.05% (6mL) PATANOL (olopatadine) Ophthalmic Solution: 0.1% (5mL) LASTACAFT (alcaftadine) Ophthalmic Solution: 0.25% (3mL) NOTE: Patient must meet #1 & #2 criteria for approval of PA request. PA CRITERIA FOR APPROVAL: 1. Documented trial and failure or intolerance to Zaditor OTC, Alaway OTC, Zyrtec Itchy Eye OTC or Ketotifen OTC (first line agents) for at least 2 weeks (14 days) of therapy. 2. Documented trial and failure or intolerance to Pataday (second line agent) for at least 2 weeks (14 days) of therapy. If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Alaway OTC: For the temporary relief of itchy eyes due to ragweed, pollen, grass, animal hair and dander. Zaditor OTC: For the temporary relief of itchy eyes due to ragweed, pollen, grass, animal hair and dander. Zyrtec Itchy Eye OTC: For the temporary relief of itchy eyes due to ragweed, pollen, grass, animal hair and dander. Pataday: For the treatment of ocular itching associated with allergic conjunctivitis. Patanol: For the treatment of the signs and symptoms of allergic conjunctivitis. Bepreve: Treatment of itching associated with allergic conjunctivitis. Elestat: For the prevention of itching associated with allergic conjunctivitis. Emadine: For the prevention of itching associated with allergic conjunctivitis. Lastacaft: For the prevention of itching associated with allergic conjunctivitis. Optivar: Treatment of itching of the eye associated with allergic conjunctivitis. NOTE: All of these agents are indicated for patients 3 years of age and older (Lastacaft is for age 2 and older). DOSAGE AND ADMINISTRATION: Alaway OTC: Put 1 drop in the affected eye(s) twice daily, every 8-12 hours, no more than twice per day. Zaditor OTC: Put 1 drop in the affected eye(s) twice a day, every 8-12 hours, no more than twice per day. Zyrtec Itchy Eye OTC: Put 1 drop in the affected eye(s) twice a day, every 8-12 hours, no more than twice per day. Pataday: Put 1 drop into each affected eye once a daily. Patanol: Put 1 drop into each affected eye two times per day at an interval of 6-8 hours. Bepreve: Put 1 drop into each affected eye twice a day. Elestat: Put 1 drop in each eye twice daily. Treatment should be continued throughout the period of exposure, even when symptoms are absent. Emadine: Put 1 drop into each affected eye up to 4 times daily. Lastacaft: Put 1 drop into each affected eye once a daily. Optivar: Put 1 drop into each affected eye twice a day.

REFERENCES: 1. Alaway OTC. Prescribing Information. Bausch & Lomb Incorporated. Available from: http://www.bausch.com/en_us/consumer/visioncare/product/drops/alaway_con.aspx. Accessed April 2010. 2. Zaditor. Novartis. Available from: http://www.zaditor.com. Accessed April 2010. 3. Zyrtec Itchy Eye Drops. McNeil. Available from: http://www.zyrtec.com/econsumer/zyrtec/product.view?body=/zyrtec/pages/prod_adults.jsp&s=prod_adults& p=11&t=. Accessed April 2010. 4. Pataday. Prescribing Information. Alcon Laboratories. August 2010. 5. Patanol. Prescribing Information. Alcon Laboratories. January 2007. 6. Bepreve. Prescribing Information. Ista Pharmacueticals, Inc. January 2010. 7. Elestat. Prescribing Information. Allergan, Inc. August 2008. 8. Emadine. Prescribing Information. Alcon Laboratories. January, 2010. 9. Optivar. Prescribing Information. Meda Pharmaceuticals. April 2009. 10. Lastacaft. Prescribing Information. Vistakon Pharmaceuticals. September 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ORAL DIABETIC AGENTS FORMULARY STATUS: Formulary JANUMET (sitagliptin/metformin) Tablet: 50/500mg, 50/1000mg JANUVIA (sitagliptin) Tablet: 25mg, 50mg, 100mg ONGLYZA (saxagliptin) Tablet: 2.5mg, 5mg STARLIX (nateglinide) Tablet: 60mg, 120mg KOMBIGLYZE TM XR (saxagliptin/metformin ER) Tablet: 2.5/500mg, 2.5/1000mg, 5/1000mg JUVISYNC (sitagliptin/simvastatin) Tablet: 100/10mg, 100/20mg, 100/40mg PA CRITERIA FOR APPROVAL: Diagnosis of Type 2 diabetes mellitus. AND Documented trial and failure with therapeutic doses, contraindication, or intolerance to at least one formulary sulfonylurea. OR Documented trial and failure with therapeutic doses, contraindication, or intolerance to metformin. OR Documented insulin therapy. If the above conditions are met, the request will be approved with a12 month duration. If the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. REFERENCES: 1. Janumet. Product Information. Merck & Co., Inc. April 2011. 2. Januvia. Product Information. Merck & Co., Inc. February 2010. 3. Kombiglyze XR. Product Information. Bristol-Myers Squibb. November 2010. 4. Onglyza. Prescribing Information. Bristol-Myers Squibb. February 2011. 5. Starlix. Prescribing Information. Novartis. July 2008. 6. Juvisync. Prescribing Information. Merck & Co., Inc. October 2011. 7. Drugdex Inc. Micromedex Healthcare Series. 2011. Available from http://.thomsonhc.com. 8. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 9. Texas Diabetes Council. Glycemic control algorithm for type 2 diabetes mellitus in children and adults. October 25, 2007. Available from: http://www.texasdiabetescouncil.org. Accessed October 30, 2009. 10. American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control. Endocrine Practice 2009;15(6):540-59. 11. American Diabetes Association. Standards of medical care in diabetes 2010. Diabetes Care. January 2011;33(suppl 1):S11-S61. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA OXYCONTIN (oxycodone extended release) Tablet: 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Chronic Pain: Diagnosis of chronic pain requiring an opioid analgesic AND Documented trial and failure or intolerance to sustained-release morphine sulfate AND Documented trial and failure or intolerance to fentanyl patches If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Management of moderate-to-severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. Not intended for use as a prn analgesic. DOSAGE AND ADMINISTRATION: OxyContin tablets are to be swallowed whole and are not to be broken, chewed, or crushed. Taking broken, chewed, or crushed tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone. Patients should be started on the lowest appropriate dose. OxyContin 60mg and 80mg tablets, or a single dose greater than 40mg, are for use in opioid-tolerant patients only. A single dose greater than 40mg, or total daily doses greater than 80mg, may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioid. The concomitant use of Oxycontin with CYP3A4 inhibitors may result in increased effects and potentially fatal respiratory depression. REFERENCES: 1. American Cancer Society (ACS). National Comprehensive Cancer Network (NCCN). Cancer Pain. Treatment Guidelines for Patients. Version II. August 2005. 2. World Health Organization. Geneva. 1996. Cancer Pain Relief. Second Edition. With a guide to Opioid Availability. 3. National Institutes of Heath. National Heart, Lung and Blood Institute. Division of Blood Diseases and Resources. The Management of Sickle Cell Disease. NIH Publication No. 02-02117. June 1997, Revised June 2002. 4. Schneir AB, et al. Massive OxyContin ingestion refractory to naloxone therapy. Ann Emerg Med 2002 Oct;40(4): 425-8. 5. Wasserman S. States respond to growing abuse of painkiller. State Legis 2001 Oct-Nov;27(9):33-4. 6. Citron ML, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998;16(8):562-71. 7. Rischitelli DG, et al. Safety and efficacy of controlled-release oxycodone: a systematic literature review. Pharmacotherapy 2002 Jul;22(7):898-904. 8. Stambaugh JE, et al. Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients. J Clin Pharmacol 2001 May;41(5):500-6. 9. Neighbors DM, et al. Economic evaluation of the fentanyl transdermal system for the treatment of chronic moderate to severe pain. J Pain Symptom Manage 2001 Feb;21(2):129-43. 10. Mucci-LoRusso P, et al. Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain 1998;2(2):239-249. 11. OxyContin (oxycodone controlled release). Prescribing Information. Purdue Pharma L.P. September 2009. 12. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PEDICULICIDES FORMULARY STATUS: Formulary, Pays at Point-of-Sale (First Line) PERMETHRIN OTC Lotion / cream rinse and liquid: 1% (Quantity Limit 120ml) PYRETHRINS/PIPERONYL BUTOXIDE OTC Shampoo: 0.33%/4% (Quantity Limit 120ml) FORMULARY STATUS: Formulary, Requires Step Therapy (Second Line) NATROBA (spinosad) Topical Suspension: 0.9% (Quantity Limit 120ml) LINDANE Shampoo: 1% (Quantity Limit 60ml) OVIDE (malathion) Lotion: 0.5% (Quantity Limit 60ml) ULESFIA (benzyl alcohol) Lotion: 5% (Quantity Limit 48oz) NOTE: Patient must meet #1 and #2 criteria for initial approval of PA request. PA CRITERIA FOR APPROVAL: 1. Diagnosis of pediculus capitus (head lice and its eggs). 2. Documented intolerance or hypersensitivity to a first line agent. or Documented trial and failure of a first line agent within the previous 45 days, but no earlier than 7 days after the original fill If the above conditions are met, the request will be approved. If the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR RENEWAL: 1. Natroba can be approved for a second treatment if live lice are present 7 days after the initial treatment. 2. Ovide and Ulesfia can be approved for a second treatment if live lice are present 7-9 days after the initial treatment. If either of the above conditions are met, the request will be approved for a maximum of 2 treatments in a 30 day period. If the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Permethrin (lotion /cream rinse and liquid): Treatment of head lice (Pediculus humanus capitus) and its nits (eggs). Pyrethrins/piperonyl butoxide (shampoo): Treatment of infestations of head lice, body lice, and pubic (crab) lice and their eggs. Natroba (topical suspension): Topical treatment of head lice infestation in patients 4 years of age and older. Lindane (shampoo): Treatment of head lice (Pediculosis humanus capitis), crab lice (Pthirus pubis), and their ova only in patients who have failed or cannot tolerate other approved therapies. The CDC recommends this agent not be used in infants and children less than 2 years old. Ovide (lotion): Indicated for patients infested with Pediculus humanus capitus (head lice and their ova) of the scalp hair in patients 6 years old. Ulesfia (lotion): Indicated for the topical treatment of head lice infestation in patients 6 months of age and older. Ulesfia does not have ovicidal activity. DOSAGE AND ADMINISTRATION: Permethrin (lotion /cream rinse and liquid): About 30-60ml of the cream rinse should be applied to washed and towel dried hair and allowed to remain for 10 minutes, and then rinsed with water. Repeat application if lice are still present after 7-10 days. Pyrethrins with piperonyl butoxide: Apply shampoo to dry hair and leave on for 10 minutes, then add warm water to form a good lather, wash, and thoroughly rinse with water until all lather is gone. Dry the hair with a clean towel and comb with a fine tooth comb to remove any remaining nits. Second treatment is recommended 7 days after initial treatment. Lindane (shampoo): Shampoo should be applied to hair that is clean and completely dry without adding water. The shampoo should be worked into the hair and allowed to remain in place for 4 minutes only and then rinse. No more than 2 ounces (60ml) should be dispensed for larger adults. DO NOT REPEAT. Natroba (topical suspension): Shake the bottle well. Apply sufficient topical suspension to cover the dry scalp, then apply to dry hair. Leave on for 10 minutes, then thoroughly rinse off with warm water. If live lice are seen 7 days after the first treatment, a second treatment should be applied.

Ovide (lotion): Apply to dry hair until the scalp and hair are thoroughly coated, allow hair to naturally dry for 8-12 hours then thoroughly wash hair. If lice are present after 7-9 days repeat application. Ulesfia (lotion): Using the guidelines below, apply sufficient Ulesfia lotion to dry hair to completely saturate the scalp and hair. Leave on for 10 minutes then thoroughly rinse off with water. Repeat treatment after 7 days to get rid of lice that hatched from eggs. Hair Length (inches) Amount of Ulesfia Lotion Per Treatment Ounces 4 oz bottle 8 oz bottle Short 0-2 4-6 oz 1-1 ½ ½ - ¾ bottle bottles 2-4 6-8 oz 1 ½ - 2 ¾ - 1 bottle bottles Medium 4-8 8-12 oz 2-3 bottles 1 - ½ bottles 8-16 12-24 oz 3-6 bottles 1 ½ - 3 bottles Long 16-22 24-32 oz 6-8 bottles 3-4 bottles Over 22 32-48 oz 8-12 bottles 4-6 bottles BOXED WARNING: Seizures and deaths have been reported following Lindane (shampoo) use with repeat or prolonged application, but also in rare cases following a single application according to directions. Lindane shampoo should be used with caution in infants, children, the elderly, and individuals with other skin conditions, and those who weigh <110 lbs (50 kg) as they may be at risk of serious neurotoxicity. It is contraindicated in premature infants and individuals with known uncontrolled seizure disorders. REFERENCES: 1. McEvoy GK, editor. Scabicies and Pediculicides. American Society of Health System Pharmacists (AHFS) Drug Information 2006. 84:04.12: 3438-3450. 2. Clark, L et al. Therapy for Head Lice Based on Life Cycle, Resistance, and Safety Considerations. Pediactrics 2007. 119; 965-974. 3. Ross K. Head Lice, Resistance, and Malathion. Pediactrics 2008; 121;222. 4. Eyerdam, DH et al. A Randomized, Investigator-Blinded Time Ranging Study of Comparative Efficacy of 0.5% Malathione Gel Versus Ovide Lotion (0.5% Malathion) of Nix Crème Tinse (1% Permethrin) Use as Labeled, for the Treatment of Head Lice. Pediactric Dermatology 2007; 405-411. 5. Facts and Comparisons, St. Louis, efacts 2011 CliniSphere Version ISBN 1-57439-036-8. 6. Drugdex In: Micromedex Healthcare Series. 2010. Available from: http://www.thomsonhc.com. Accessed July 2010. 7. Ovide Prescribing Information. Taro Pharmaceuticals USA. October 2009. 8. Lindane Prescribing Information. Morton Grove Pharmaceuticals Inc. June 2010. 9. Ulesfia Prescribing Information. Sciele Pharma, Inc. April 2009. 10. Natroba Prescribing Information. ParaPRO LLC. January 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION PROCESS FOR INJECTABLE/SPECIALITY MEDICATIONS WITH NO SPECIFIC PRIOR AUTHORIZATION PROTOCOL Initial Approval 1. The request for the medication is for an FDA approved indication, and/or is used for a medical condition that is supported by the medical compendium (Micro Medex, American Hospital Formulary Service, Drug Points, and Drug Package Insert) as defined in the Social Security Act 1927 and/or per recognized standard of care guidelines. 2. There is no formulary or plan preferred medication alternatives, OR there is a documented medical reason (i.e. medical intolerance, treatment failure, etc.) for why a formulary or plan preferred medication couldn t be used to treat the member s condition. 3. Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined above and/or per recognized standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 16 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per recognized standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director (or Psychiatrist when applicable) for medical necessity review. Reauthorization of Medication 1. The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per recognized standard of care guidelines. 2. Prescribed dosing of medication is within FDA approved indications or per supported by the medical compendium as defined above and/or per recognized standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 16 weeks or as recommended per FDA approved indications and/or as defined by medical compendium as defined above and/or per recognized standard of care guidelines; if all of the above criteria are not met, the request is referred to a Medical Director (or Psychiatrist when applicable) for medical necessity review. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Psychiatrist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PROCRIT (epoetin alfa): 2,000 units/ml, 3,000 units/ml, 4,000 units/ml, 10,000 units/ml, 20,000 units/ml, 40,000 units/ml PA CRITERIA FOR APPROVAL: The necessary lab work (listed below) is performed within 30 days of the date the request is submitted and is either documented on the PA form or submitted with the request -Hemoglobin -Hematocrit -Serum ferritin -Transferrin saturation (TSAT) -Serum iron -Total Iron Binding Capacity (TIBC) -Vitamin B12 level -Folate level -Erythropoietin level (for HIV related anemia) Documentation submitted indicates the member has Chronic Kidney Disease related anemia and/or Chemotherapy related anemia, or an anemia related to some other medical condition. If all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. If all of the above conditions are met, place the member into one of the following categories based on diagnosis: -Treatment of anemia of Pre-dialysis in chronic kidney disease patients: go to Section I -Treatment of anemia in cancer patients undergoing chemotherapy: go to Section II -Prescribed for anemia in HIV and/or Zidovudine-treated HIV disease: go to Section III -Reduction of allogeneic blood transfusion in surgery patients: go to Section IV -Prescribed for Ribavrin Induced anemia: go to Section V -Prescribed for other Medically Acceptable Indications go to Section VI Section I: PA Criteria for Approval for anemia in chronic kidney disease Place the member into one of the following categories based on the members Procrit treatment history. - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B) Part A: Procrit treatment initial request If the member has chronic renal failure, the member has a hemoglobin level < 10 g/dl Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section). Documentation submitted indicates that the member is or will be prescribed maintenance iron therapy (>200 mg elemental iron orally daily or periodic IV supplementation), or if not receiving iron supplementation is having percentage transferrin saturation and ferritin levels checked every 2 months. If the member has low vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy and will be having percentage transferrin saturation and ferritin levels monitored. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if

the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit If the member has chronic renal failure, and has been receiving therapy and their hemoglobin is <10 g/dl(submitted lab result dated within 30 days of request), AND if one of the following apply: a. Ordered dose of Procrit is reduced by 25% of previous dose if the member s Hgb is increasing by more than 1 g/dl in a 2 week period, b. Ordered dose of Procrit was increased and Hgb increase rate was < 1 g/dl over the past 4 weeks AND the member has adequate iron stores AND the Hgb remains less than 10 g/dl c. No more than 1 dosage adjustment per 4 week intervals occurs If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 and/or Folate based on lab results from the initial request and are NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. The member s percentage transferrin saturation is greater than 20% and Ferritin is greater than 100 ng/ml and the member is receiving iron supplementation, if not receiving iron supplementation percentage transferrin saturation and Ferritin levels are being monitored every 2 months If the patient does no respond to treatment as measured by hemoglobin levels or if RBC transfusions are still required after 8 weeks of therapy then the provider must submit a valid medical reason for continuation of therapy. Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved for up to a 3-month duration, if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR up to a 1 month temporary supply if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient. If all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Section II: PA Criteria for Approval for anemia in cancer patients on chemotherapy: Place the member into one of the following categories based on the members Aranesp treatment history. - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B) Part A: Procrit treatment initial request The member has a documented hemoglobin < 10 g/dl OR if the member is new to the health plan and was receiving Procrit at the previous health plan and the member has a documented hemoglobin < 12g/dL Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) Documentation that the patient is currently receiving chemotherapy (along with documentation of the start and end date of the current course of chemotherapy). Treatment with Procrit should be discontinued at the completion of a course of chemotherapy. If all of the above conditions are met, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first), if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested.

Part B: Reauthorization Criteria for Procrit The member has been receiving therapy and their hemoglobin is < 12 g/dl Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the dose of Procrit is being increased and/or patient s hemoglobin level has decreased from the previous request then recent (within 30 days of the request) ferritin, percentage transferrin saturation, Vitamin B12 and Folate levels are to be submitted. In addition: o If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), AND in the process of receiving either oral or IV iron supplementation OR the treatment plan is to start iron therapy along with having the percentage transferrin saturation and ferritin levels monitored. o If the member has low Vitamin B12 levels and/or Folate levels, documentation submitted indicates that the member is OR will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If all of the above conditions are met, and the member is not functionally iron (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%), Vitamin B-12 and Folate deficient OR if the member is iron, vitamin B12 and/or folate deficient and receiving the proper supplementation, the request will be approved for up to a 6-month duration OR till the end of current course of chemotherapy (whichever comes first). However, up to a 1 month temporary supply will be approved if the member is functionally iron (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or Vitamin B-12 or Folate deficient AND not receiving OR planning to start the proper supplementation. If the above criteria is not met, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Section III: PA Criteria for Approval for Treatment of Anemia due to HIV and/or Zidovudine-treated HIV disease Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B) Part A: Procrit treatment initial request The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl Patient has been receiving a highly active antiretroviral therapy (HAART) regimen for the past 35 days. Documentation, within 30 days of the request, that the patient has an erythropoietin level < 500 milliunits/ml and receiving < 4200 mg/week of Zidovudine treatment. If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), documentation is submitted indicating that the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. The requested dose is in accordance with the recommended dosing guidelines as outlined in the dosage and administration section for HIV patients below. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month

may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit If the member has been receiving therapy and their hemoglobin is < 11 g/dl (submitted lab result dated within 30 days of request), OR if one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period b. The ordered dose of Procrit is increased by 25% of previous dose if the patient s Hgb has not increased by 1 g/dl over a 4 weeks period (See Dosage and Administration section) OR the patient s Hgb falls below 10 g/dl. c. An increase in dose does not occur more than once per month. Patient is currently receiving HAART therapy. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Section IV: PA Criteria for Approval for Reduction of Allogeneic Blood Transfusion in Surgery Patients The member has a hemoglobin level >10 to < 13 g/dl (submitted lab result dated within 30 days of request). The member is scheduled for an elective noncardiac, nonvascular surgery and need to reduce the need for allogeneic blood transfusions. The patient has normal iron stores and is, or will be, receiving adequate iron supplementation The patient is starting therapy and the dose is within the starting dosage range [300 U/kg/day SC for 10 days before surgery, on the day of surgery and for 4 days after surgery OR 600 U/kg SC in once-weekly doses (21, 14 and 7 days before surgery) plus a fourth dose on the day of surgery] If all of the above conditions are met, the request will be approved with a 1-month duration; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Section V: PA Criteria for Approval for Ribavirin Induced Anemia Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B) Part A: Procrit treatment initial request

The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. Patient is currently receiving ribavirin therapy and initiated therapy 20 weeks ago. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Part B: Reauthorization Criteria for Procrit If the member has been receiving therapy and their hemoglobin is < 11 g/dl(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dl & one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Procrit is increased if the patient s Hgb has not increased by 1 g/dl over a 4 weeks period (See Dosage and Administration section) OR the patient s Hgb falls below 10 g/dl. c. An increase in dose does not occur more than once per month. The member is currently receiving ribavirin therapy that was initiated 20 weeks ago, or if beyond week 20 of ribavirin therapy, documentation submitted indicates a dosage reduction of ribavirin to 600 mg/day after week 20 but the member still became anemic. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy. Procrit ordered dose is consistent with approvable dosing guidelines (See Below - Dose and Administration section) If all of the above conditions are met, the request will be approved with a 3-month duration or up to the member completes Ribavirin therapy (24-48 weeks of treatment), if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Section VI: PA Criteria for Approval for Treatment of Other Medically Acceptable Indications Place the patient into one of the following: - Procrit treatment initial request (Part A) - Reauthorization of Procrit (Part B)

Part A: Procrit treatment initial request Documentation was forwarded indicating the medication (including dose) was prescribed or recommended by a hematologist or a specialist in the respective disease state associated anemia. The member has a hemoglobin level < 11 g/dl OR if the member is new to the health plan and was receiving Procrit at the previous health plan the member has a documented (submitted lab result dated within 30 days of request) hemoglobin <12 g/dl Procrit is ordered be administered 2 to 3 times a week unless the patient has a medical reason for only receiving the medication on a once weekly basis If the member has low vitamin B12 levels and/or Folate levels then documentation submitted that indicates the member is or will be prescribed appropriate supplementation with vitamin B12 and/or Folic acid as indicated. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation (>200 mg elemental iron orally daily or periodic IV supplementation) or the treatment plan is to start iron therapy and then have the percentage transferrin saturation and ferritin levels monitored. The member has had a documented treatment failure at optimal doses of Aranesp and/or intolerance to Aranesp, and/or some other documented clinically significant reason for not using Aranesp to treat their anemia. Based on compendia and standard of care clinical guidelines, the Procrit ordered dose is consistent with approvable dosing guidelines for the medically acceptable indication being treated. (See Below - Dose and Administration section. If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) and not vitamin B-12 deficient and not folate deficient, OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. Reauthorization Criteria for Procrit If the member has been receiving therapy and their hemoglobin is < 11 g/dl(submitted lab result dated within 30 days of request), OR if hemoglobin (submitted lab result dated within 30 days of request) is > 11g/dL < 12 g/dl & one of the following apply: a. The ordered dose of Procrit is reduced by 25% of previous dose if the rate of Hgb increase was > 1g/dL over a two week period OR the Hgb is increasing and approaching 12 g/dl. b. The ordered dose of Procrit is increased by 25% of the previous dose if the patient s Hgb has not increased by 1 g/dl over a 4 weeks period (See Dosage and Administration section) OR the patient s Hgb falls below 10 g/dl. c. An increase in dose does not occur more than once per month. Based on compendia and standard of care clinical guidelines, the Procrit ordered dose is consistent with approvable dosing guidelines for the medically acceptable indication being treated. (See Below - Dose and Administration section. If the member had a normal vitamin B12 and Folate levels on the initial request OR had a low vitamin B12 and/or Folate level but has subsequently been placed on the appropriate supplementation then repeat vitamin B12 and Folate lab results are not needed until 1 year after the initial request. However if the patient was deficient in either vitamin B12 or Folate levels based on lab results from the initial request and is NOT receiving the appropriate supplementation then repeat vitamin B12 and Folate lab results must be submitted dated within 30 days of the request. If the member is iron deficient (ferritin concentration <100 ng/ml and/or percentage transferrin saturation < 20%), the member is in the process of receiving either oral or IV iron supplementation or the treatment plan is to start iron therapy.

If all of the above conditions are met, the request will be approved for up to a 3-month duration if the member is not functionally iron deficient (ferritin concentration is > 100-800 ng/ml and the transferrin saturation are > 20-55%) OR a temporary supply of up to 1 month may be authorized if the member is functionally iron deficient (ferritin concentration < 100 ng/ml and/or percentage transferrin saturation < 20%) and/or vitamin B-12 deficient and/or folate deficient; if all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. FDA INDICATIONS: Treatment of anemia of chronic renal failure patients Treatment of anemia in Zidovudine-treated HIV-infected patients Treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. o Procrit is not indicated for use in patient receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy o Procrit is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is sure due to the absence of studies that adequately characterize the impart of Procrit on progression-free and overall survival o Procrit is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate o deficiencies, hemolysis, or gastrointestinal bleeding Procrit use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being Treatment of anemic patients (Hgb > 10 to < 13 g/dl) who are at high risk for perioperative blood loss form elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions DOSAGE AND ADMINISTRATION: Therapeutic Guidelines in CKD Patients ON Dialysis for Epoetin Alfa Starting dose Subcutaneous or Intravenous administration (IV preferred) Maximum dose (with normal Iron stores) Adults50-100 units/kg 3 times/week Pediatric: 50 units/kg 3 times weekly 300 units/kg/week Subcutaneous administration **Doses greater than maximum doses require hematologist consultation and recommendation. If adjusting therapy Reduce dose 25% when: Dose should be temporarily withheld when Increase dose up to 25% of previous dose if: Consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability Do not increase the dose more frequently than once every 4 weeks 1). Hemoglobin approaches 11 g/dl OR 2). Hemoglobin increases by more than 1.0 g/dl in 2-week period Hemoglobin exceeds or approaches 11 g/dl and until hemoglobin falls to 11 g/dl. Therapy should be reinitiated at a dose approximately 25% below the previous dose. 1. Hemoglobin is < 10 g/dl and has not increase by 1g/dL over a 4 week period OR 2. Hemoglobin decreases below 10 g/dl

Maintenance dose Suggested target Hemoglobin Monitor AND 3. Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/ml) Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 11 g/dl. <11 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 11 g/dl Hemoglobin levels at least weekly until stable and then monitor monthly Therapeutic Guidelines in CKD Patients NOT ON Dialysis for Epoetin Alfa Starting dose Subcutaneous or Intravenous administration 50-100 units/kg 3 times/week Maximum dose (with normal Iron stores) 300 units/kg/week Subcutaneous administration **Doses greater than maximum starting dose requires hematologist consultation and recommendation. If adjusting therapy Consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability Do not increase the dose more frequently than once every 4 weeks Reduce dose 25% when: 1). Hemoglobin approaches 10 g/dl OR 2). Hemoglobin increases by more than 1.0 g/dl in 2-week period Dose should be temporarily withheld Hemoglobin exceeds or approaches 10

when g/dl and until hemoglobin falls to 10 g/dl. Therapy should be reinitiated at a dose approximately 25% below the previous dose. Increase dose up to 25% of previous dose if: Maintenance dose Suggested target Hemoglobin Monitor 1. Hemoglobin is has not increased by 1g/dL over a 4 week period AND 2. Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/ml) Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 10 g/dl. <10 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 11 g/dl Hemoglobin levels at least weekly until stable and then monitor monthly B. Zidovudine-treated, HIV-infected patients: Therapeutic Guidelines in Zidovudine-treated, HIV-infected patients for Epoetin Alfa: Starting dose Subcutaneous or Intravenous administration Maximum dose (with normal Iron stores) 100 units/kg three times a week 300 units/kg three times a week Subcutaneous or Intravenous administration *Doses greater than maximum doses require hematologist consultation and recommendation.* Reduce dose 25% when: Dose should be temporarily withheld when 1) Hemoglobin approaches12 g/dl OR 2) Hemoglobin increases by more than 1.0 g/dl in 2-week period Hemoglobin exceeds 12 g/dl and until hemoglobin falls to 11 g/dl. Therapy should be reinitiated at a dose approximately 25% below the previous

Increase dose up to 25% of previous dose if: Maintenance dose Suggested target Hemoglobin Discontinue therapy if: dose. 1) Hemoglobin is < 10 g/dl and has not increased by 1g/dL over a 4 week period OR 2) Hemoglobin decreases below 10 g/dl AND 3) Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/ml) Individualize to achieve and maintain the lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. If hemoglobin does not increase after 8 weeks, increase dose by about 50-100 units/kg at 4-8 week intervals until hemoglobin reaches a level sufficient to avoid RBC transfusion <12 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl Hemoglobin increase is not achieved with 300 units/kg for 8 weeks C. Anemia due to chemotherapy: Therapeutic Guidelines in Anemia due to Chemotherapy for Epoetin Alfa: Starting dose Subcutaneous administration for adult patients: Initial administration for pediatric patients Maximum dose (with normal Iron stores) Reduce dose 25% when: Therapy should be discontinued when: Increase dose up to: For adult patients 60,000 units weekly OR 300 units/kg three times a week For pediatric patients 900 units/kg (maximum 60,000 units) Maintenance dose 150 units/kg three times a week or 40,000 units weekly 600 units/kg (maximum 40,000 units) intravenously weekly For adult patients 60,000 units weekly or 300 units/kg three times week SC For pediatric patients 900 units/kg (maximum 60,000 units) IV 1). Hemoglobin increases by more than 1.0 g/dl in 2-week period The current course of chemotherapy has been completed. 1) If hemoglobin has not increased by greater than 1 g/dl after 4 weeks of therapy in the absence of a red blood cell transfusion AND 2) Dosage increases should occur only after treating and/or ruling out functional iron deficiency anemia (TSAT <20% and Ferritin <100 ng/ml) Individualize to achieve and maintain the

Suggested target Hemoglobin lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl. The lowest dose needed to avoid the need for RBC transfusion. D. Guidelines for the use of Procrit in Surgery Patients: Prior to initiating treatment with Procrit, obtain a hemoglobin to establish that it is > 10 to <= 13 g/dl. The recommended dose is 300 U/kg/day SC for 15 days total: 10 days before surgery, on the day of surgery and for 4 days after surgery. An alternate dose schedule is 600 U/kg SC in 4 doses administered 21, 14 and 7 days before surgery and on the day of surgery. All patients should receive adequate iron supplementation. Initiate iron supplementation no later than the beginning of treatment with Procrit and continue throughout the course of therapy. Deep venous thrombosis prophylaxis should be strongly considered. E. Guidelines for the use of Epoetin Alfa for Ribavirin Induced Anemia Initial therapy Studies using Procrit to treat ribavirin induced anemia typically used a 40,000 unit once per week. Based on the National Comprehensive Cancer Network guidelines, Procrit 40,000 units weekly is equivalent to 30,000 units per week if 30,000 units are divided into10,000 units to be administered 3 times over one week.. Therefore, approvable Procrit initial total weekly doses should not exceed 30,000 units/week administered in 2-3 divided doses over one week (i.e. 10,000 units three times weekly or 15,000 units in prefilled syringes twice weekly). Procrit 40,000 units once weekly will be approved if the member has a medical reason for not being able to receive Procrit 30,000 units/week divided evenly into 2-3 doses over one week. Length of therapy Medication should only be approved while the member is within the first 20 weeks of receiving Ribavirin and Interferon therapy to treat their Hepatitis C infection. If the member is to receive Interferon and Ribavirin therapy for greater than 20 weeks because they eradicated the HCV virus, the dose of Ribavirin at that time should be reduced to 600 mg/day, and if the member becomes anemic, then Procrit maybe reauthorized to treat the members anemia in order for the member to stay on 600 mg of Ribavirin a day. Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dl in a 2-week period Or If the Hgb is increasing and approaching 12 g/dl. o Temporarily hold dose when: Hgb exceeds 12 g/dl and until Hgb falls below 11g/dL Therapy can be reinitiated at a dose approximately 25% below the previous dose o Increase dose by 25%, if the member s Hgb does not increase 1 g/dl after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient, and after member s ribavirin dose was reduced to 600 mg /day. o Target Hgb: <12 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl F. Other Medically Acceptable Indications Dosing Guidelines: Based on the medical compendia (Drug Points, Micro Medex, AHFS) and standard of care clinical guidelines, the dose is appropriate for the medically acceptable indication being treated, Dosage adjustments: o Decrease dose by 25% when: Hgb increases by > 1.0 g/dl in a 2-week period

Or If the Hgb is increasing and approaching 12 g/dl. o Temporarily hold dose when: Hgb exceeds 12 g/dl and until Hgb falls below 11g/dL Therapy can be reinitiated at a dose approximately 25% below the previous dose o Increase dose by 25%, if the member s Hgb does not increase by 1 g/dl after 4 weeks of therapy as long as the member is not iron, vitamin B12 and folate deficient. Target Hgb: <12 g/dl or lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dl Conversion from epoetin alfa (Procrit) to darbepoetin: Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Because of the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if member was receiving epoetin alfa 2 to 3 times weekly. Administer darbepoetin once every 2 weeks if the member was receiving epoetin alfa once per week. Maintain the route of administration (IV or SC). Estimated Darbepoetin Starting Doses Based on Previous Epoetin Alfa Dose Previous weekly epoetin alfa dose Equivalent weekly starting darbepoetin dose (mcg) (units/week) < 2499 6.25 2500 to 4999 12.5 5000 to 10,999 25 11,000 to 17,999 40 18,000 to 33,999 60 34,000 to 89,999 100 90,000 200 TABLE 1 The Definition of Chronic Kidney Disease The KDOQI defines Chronic Kidney Disease with two independent criteria: 1. Kidney damage for > 3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either: Pathological abnormalities OR Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests 2. GFR < 60 ml/min/1.73m2 for >3 months with or without kidney damage

National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39: S1-S266, 2002 (suppl 1). REFERENCES: 1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, 2000. Am J Kidney Dis 37:S182-S238, 2001 (suppl 1) 2. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39: S1-S266, 2002 (suppl 1). Available from URL: http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. 3. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cancer and Treatment-Related Anemia. Version 2.2007. 4. Rizzo JD, Lichtin AE, Woolf SH, Seidenfeld J, Bennett CL, Cella D, Djulbegovic B, Goode MJ, Jakubowski AA, Lee SJ, Miller CB, Rarick MU, Regan DH, Browman GP, Gordon MS. Use of Epoetin in Patients With Cancer: Evidence-Based Clinical Practice Guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Journal of Clinical Oncology, Vol 20, No. 19 (October 1), 2002: pp 4083-4107. Available from URL: http://www.asco.org/asco/downloads/guidelines/2002epo.pdf 5. Lichtin A. The ASH/ASCO clinical guidelines on the use of erythropoietin. Best Practice & Research Clinical Haematology. 2005; 18(3):433-438. 6. HIV and AIDS Anemia and Fatigue. [resource on World Wide Web]. URL: http://www.hivandhepatitis.com/recent/lipo/071902_anemia.html#who 7. Int J Antimicrob Ag 1997; 8:189 8. Ortho Biotech Inc. Procrit (Epoetin Alfa). Prescribing Information, 05/2012. 9. Volberding PA, Levine AM, Dietrich D, et al. Anemia in HIV Infection: Clinical Impact and Evidence-Based Management Strategies. Clinical Infectious Diseases 2004;38:1459-68 10. Aranesp (darbepoetin alfa). Prescribing Information, Amgen. 7/2012. 11. Revision/ Rigsby M, Burgess J, and Davey V et al. VA Treatment Recommendations: Patients with Chronic Hepatitis C. Federal Practitioner Supplement. 2003; Vol 20 Suppl. 5: 1-32. 12. Shiffman M, DiBisceglie A, and Lindsay K et al. Peginterferon Alfa-2a and Ribavirin in Patients with Chronic Hepatitis C Who Have Failed Prior Treatment. Gastroenterology. 2004; Vol 126: 1015-1023. 13. http://www.chemocare.com/bio/list_by_acronym.asp?acronyn Review Date: 01/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PROTON PUMP INHIBITORS (PPIs) FORMULARY STATUS: Formulary, Pays at Point-of-Sale (First Line) PRILOSEC (omeprazole) (generic) Capsule: 10mg, 20mg, 40mg; PREVACID (lansoprazole) SoluTab: 15mg, 30mg (For members < 8 years old only) PROTONIX (pantoprazole) Tablet: 20mg, 40mg FORMULARY STATUS: Formulary, Requires Step Therapy (Second Line) PREVACID 24HR OTC (lansoprazole) Capsule: 15mg ZEGERID OTC (omeprazole/sodium bicarbonate) Capsule: 20mg/1100mg NOTE: Patient must meet criteria #1 & #2 for approval of initial PA request. FORMULARY STATUS: Non-Formulary, Requires Prior Authorization (Third Line) ACIPHEX (rabeprazole) Tablet: 20mg DEXILANT (formerly known as KAPIDEX) (dexlansoprazole) Capsule: 30mg, 60mg NEXIUM (esomeprazole) Capsule: 20mg, 40mg; Packet for Oral Suspension: 10, 20mg, 40mg PRILOSEC (omeprazole) Packet for Oral Suspension: 2.5mg, 10mg PREVACID (lansoprazole) Capsule: 15mg, 30mg; SoluTab: 15mg, 30mg (For members 8 years old) PRILOSEC OTC (omeprazole) Tablet: 20mg PROTONIX (pantoprazole) Packet for Oral Suspension: 40mg ZEGERID (omeprazole/sodium bicarbonate) Capsule: 20mg/1100mg, 40mg/1100mg; Packet for Oral Suspension: 20mg/1680mg, 40mg/1680mg NOTE: Patient must meet criteria #1, #2 & #3 for approval of initial PA request. PA CRITERIA FOR APPROVAL: 1. Presumed or documented diagnosis of duodenal ulcer, H.pylori, gastritis, gastric ulcer, GERD, erosive esophagitis, Barrett s disease or hypersecretory disease. 2. Documented trial and failure or intolerance with omeprazole 20mg or pantoprazole tablets once daily for a minimum of 3 weeks of therapy within the previous 60 days. 3. Documented trial and failure or intolerance with Prevacid 24HR 30mg once daily or Zegerid OTC 20mg/1100mg once daily for a minimum of 3 weeks of therapy. If the above conditions are met, the request will be approved with up to a 12-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review Doses Greater Than Once Daily After Meeting Criteria For PPI: 1. Confirmed diagnosis of GERD, erosive esophagitis, or hypersecretory disease. OR 2. Evaluation made by gastroenterologist and / or otolaryngologist recommending higher doses of PPI. If the above conditions are met, the request for a dose greater than once daily will be approved with a 12-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. REFERENCES: 1. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Aciphex. Prescribing Information. Eisai Co. January 2009. 3. Kapidex. Prescribing Information. Takeda Pharmaceuticals. August 2009. 4. Nexium. Prescribing Information. AstraZeneca. June 2009. 5. Prevacid. Prescribing Information. Takeda Pharmaceuticals. July 2009. 6. Prevacid 24HR. Available at: http://www.prevacid24hr.com/index.jsp. Accessed November 2009. 7. Protonix. Prescribing Information. Wyeth Pharmaceuticals. May 2008. 8. Prilosec. Prescribing Information. AstraZeneca. May 2008. 9. Prilosec OTC. Available from: http://www.prilosecotc.com/. Accessed November 2009. 10. Zegerid. Prescribing Information. Santarus. January 2008.

11. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; DOI:10.1503/cmaj.082001. Available at: http://www.cmaj.ca. 12. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-44. 13. Comparison of proton pump inhibitors. Pharmacist's Letter/Prescriber's Letter 2009;25(3):250304. 14. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of Pantoprazole and Esomeprazole on Platelet Inhibition by Clopidogrel. Am Heart J. 2009;157(1):148. 15. Proton pump inhibitor and Plavix interaction: does it exist? Pharmacist's Letter/Prescriber's Letter 2009;25(4):250401. Review Date: 11/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SOUTH REGION PRIOR AUTHORIZATION CRITERIA PROTOPIC (tacrolimus) Ointment: 0.03%, 0.1% PA CRITERIA FOR APPROVAL STATUS Requires PA INITIAL PA: Diagnosis of moderate to severe atopic dermatitis. AND Non-immunocompromised patient. AND Patient 2 years of age or older. AND Patient has not adequately responded to two different preferred prescription strength corticosteroid therapies in the last 8 weeks. OR Physician provides valid rationale why corticosteroid therapy is inappropriate (ex., use on the face). If the above conditions are met, the request will be approved with a 3 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. RENEWAL PA: Diagnosis of moderate to severe atopic dermatitis. Non-immunocompromised patient. Patient 2 years of age or older. Documentation that patient has been re-examined by their health care provider and continuation of Protopic therapy is appropriate. If the above conditions are met, the request will be approved with a 6 month duration; if the above conditions are not met, the request will be referred for medical necessity review. FDA INDICATIONS Moderate to Severe Atopic Dermatitis: Protopic Ointment, both 0.03% and 0.1% for adults, and only 0.03% for children aged 2 to 15 years, is indicated as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non-immunocompromised adults and children who have failed to respond adequately to other topical prescription treatments for atopic dermatitis, or when those treatments are not advisable. DOSAGE AND ADMINISTRATION Adults (0.03% and 0.1%): Apply a thin layer to the affected skin areas twice daily and rub in gently and completely. Children 2-15 Years (0.03%): Apply a thin layer to the affected skin areas twice daily and rub in gently and completely. ***Protopic should not be used with occlusive dressings. ***Stop using when signs and symptoms of atopic dermatitis resolve. ***If signs and symptoms persist beyond 6 weeks, patients should be re-examined by their health care provider to confirm diagnosis of atopic dermatitis. ***Continuous long-term use of topical calcineurin inhibitors, including Protopic should be avoided, and application should be limited to areas of involvement with atopic dermatitis.

REFERENCES 1. Protopic. Prescribing Information. Astellas Pharma US, Inc. May 2012. 2. Hanifin JM, Cooper KD, Ho VC, Kang S, et al. Guidelines of care for atopic dermatitis. J Am Acad Dermatol 2004;50(3):485-6. 3. Russell JJ. Topical tacrolimus: a new therapy for atopic dermatitis. Am Fam Physician, Nov 15 2002;66(10):1899-902. 4. Bergman J, Rico MJ. Tacrolimus clinical studies for atopic dermatitis and other conditions. Semin Cutan Med Surg, Dec 2001;20(4):250-9. 5. Reitamo S, Harper J, Bos JD, et al. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double blind controlled trial. Br J Dermatol. Mar 2004;150(3):554-62. Revision/Review Date: 7/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Reviewer must override criteria when. in his/her professional judgment. the requested itemis medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA PULMICORT RESPULES (budesonide) Inhalation Suspension: 0.25mg/2mL, 0.5mg/2mL, 1mg/2mL FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Diagnosis of chronic asthma for patients 8 years of age and younger will process at the point of sale without prior authorization required if dosed within appropriate dosing guidelines as follows: -0.25mg/2mL once daily -0.5mg/2mL once daily or twice daily -1.0mg/2mL once daily A dose of 0.25mg/2mL twice daily will be approved if prescriber indicates that once daily dosing is not efficacious and determines that increasing the dose (i.e. 0.5mg/2mL once daily) is not appropriate for the patient. All other requests will be referred to a Medical Director for medical necessity review. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Asthma, chronic: For the maintenance treatment of asthma and as prophylactic therapy in children 12 months to 8 years of age. It is not indicated for the relief of acute bronchospasm. DOSAGE AND ADMINISTRATION: Administer by the inhaled route via jet nebulizer connected to an air compressor in asthmatic patients 12 months to 8 years of age. Individual patients will experience a variable onset and degree of symptom relief. Improvement in asthma control following inhaled administration of budesonide can occur within 2 to 8 days of initiation of treatment, although maximum benefit may not be achieved for 4 to 6 weeks. In all patients, it is desirable to downward-titrate to the lowest effective dose once asthma stability is achieved. Children 12 months to 8 years of age: -Previously on bronchodilators alone: 0.5 mg total daily dose administered either once or twice daily in divided doses; highest recommended dose is 0.5 mg total daily dose. -Previously on inhaled corticosteroids: 0.5 mg total daily dose administered either once or twice daily in divided doses; highest recommended dose is 1 mg total daily dose. -Previously on oral corticosteroids: 1 mg total daily dose administered either as 0.5 mg twice daily or 1 mg once daily; highest recommended dose is 1 mg total daily dose. REFERENCES: 1. Pulmicort Respules. Product Information. AstraZeneca LP. July 2010. 2. National Asthma Education and Prevention Program Clinical Practice Guidelines: Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 02-5074 June 2003. http://www.nhlbi.nih.gov/guidelines/asthma/asthmafullrpt.pdf 3. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version TSBN 1-57439-036-8. 4. O Byrne PM, Pederson S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest. 2006 Jun. 129(6):1478-85. 5. Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006 May; 354(19):1998-2005. 6. Berger WE. Budesonide inhalation suspension for the treatment of asthma in infants and children. Drugs. 2005; 65(14):1973-89. 7. Berger WE, Qaqundah PY, Blake K, Rodriguez-Santana J, Irani AM, Xu J, Goldman M. Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze. J Pediatr. 2005 Jan; 146(1):91-5. 8. Masoli M, Weatherall M, Holt S, Beasley R. Budesonide once versus twice-daily administration: meta-analysis. Respirology. 2004 Nov; 9(4):528-34. 9. West KM, Culhane NS. Role of budesonide inhalation suspension in children with asthma. Ann Pharmacother. 2002 Feb; 36(2):322-5. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA FOR PULMONARY ARTERIAL HYPERTENSION (PAH) TREATMENT Adcirca (Tadalafil): Tablets 20 mg Letairis (Ambrisentan): Tablets 5mg, 10mg Revatio (Sildenafil): Tablets 20 mg Tracleer (Bosentan): Tablets 62.5 mg, 125 mg Flolan (Epoprostenol): 0.5 mg, 1.5 mg vial, powder for reconstitution Remodulin (Treprostinil): 1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml Tyvaso (Treprostinil): 2.9 ml ampules, solution for inhalation Ventavis (Iloprost): 10 mcg/ml, solution for inhalation PA CRITERIA FOR INITIAL APPROVAL: Documentation of a confirmed diagnosis of pulmonary arterial hypertension (PAH) World Health Group (WHO Group I). See Box 1. Medication is being used for an FDA approved functional class (See Box 2 & Box 3). Documentation that the patient has undergone acute vasoreactivity testing and whether or not the results were favorable. For those patients who demonstrated a favorable response to the acute vasoreactivity testing (defined as a fall in mean pulmonary arterial pressure [PAPm] of at least 10 mm Hg to < 40 mm Hg with an increased or unchanged cardiac output), then documentation that his/her pulmonary hypertension has progressed despite maximal medical treatment with a calcium channel blocker. Documentation of the patient s current weight. The medication is being recommended and prescribed by a pulmonologist or a cardiologist at a dose that is within FDA approved guidelines. If the request is for Tracleer the patient must have a documented trial and failure or intolerance to Letaris. If the request is for Remodulin or Tyvaso the patient must have a documented trial and failure or intolerance to generic epoprostenol (Flolan ) or Ventavis. If the provider is requesting combination therapy with two agents then documentation must be submitted of an adequate trial (> 3 months) with monotherapy, documentation that the patient has been compliant with the single agent, and documentation that the patient has clinically deteriorated (e.g. worsening of the symptoms of dyspnoea or fatigue, decline in functional class by at least one class or in 6-minute walk test (6MWD) by greater than 30 minutes) while on monotherapy. If all of the above conditions are met, the request for all oral treatment will be approved for up to a 6 month duration and requests for any injectable/infusible medication will be approved for up to a 16 week duration; if all of the above criteria are not met the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR REAUTHORIZATION: Dosage Increase: Documentation of the medical necessity to increase the dosage is provided. The medication is being recommended and prescribed by a pulmonologist at a dose that is within FDA approved guidelines. If all of the above conditions are met, the request for all oral treatment will be approved for up to a 6 month duration and requests for any injectable/infusible medication will be approved for up to a 16 week duration; if all of the above criteria are not met the request is referred to a Medical Director for medical necessity review. Box 1 WHO Group Classification of PAH Group I. Pulmonary arterial hypertension (PAH) Idiopathic (IPAH) Familial (FPAH) Associated with (APAH): o Connective tissue disease (systemic sclerosis (scleroderma) & systemic lupus erythematosus (SLE)) o Congenital systemic -to- pulmonary shunts o Portal hypertension o HIV infection o Drugs and toxins

Box 1 WHO Group Classification of PAH o Other (thyroid disorders glycogen storage disease, Gaucher s disease, hereditary hemorrhagic telangiectasia, haemoglobinapathies, myeloproliferative disorders, splenectomy) Associated with significant venous or capillary involvement o Pulmonary veno-occlusive disease (PVOD) o Pulmonary capillary haemangiomatosis (PCH) Persistent pulmonary hypertension of the newborn (PPHN) Group II. Pulmonary hypertension associated with left heart diseases Group III. Pulmonary hypertension associated with respiratory diseases or hypoxemia (including chronic obstructive pulmonary disease. Group IV. Group V. Pulmonary hypertension due to chronic thrombotic or embolic disease Miscellaneous group e.g. sarcoidosis, histiocytosis X, and lymphangiomatosis Box 2 NYHA & WHO Functional Classifications NYHA Functional Classification Class I: No symptoms with ordinary physical activity. Class II: Symptoms with ordinary activity. Slight limitation of activity. Class III: Symptoms with less than ordinary activity. Marked limitation of activity. Class IV: Symptoms with any activity or even at rest. WHO Functional Assessment Classification Class I: Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. Class II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. Class IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea or fatigue may even be present at rest. Discomfort is increased by any physical activity. Box 3 PAH Medications Functional Class Indications Drug FDA Approved Functional Class of Symptoms Tracleer WHO Class III and IV Revatio WHO Group I Letairis WHO Class II and III Flolan NYHA Class III and IV Remodulin NYHA Class II, III, and IV Ventavis NYHA Class III and IV FDA INDICATION: Adcirca : Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability. Letairis : Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening. Revatio : Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability and delay clinical worsening. The delay in clinical worsening was demonstrated when Revatio was added to background Flolan therapy.. Tracleer : Indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO Class III or IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Flolan : Indicated for long term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy. Tyvaso : Indicated to increase the walk distance in patients with WHO Group I pulmonary arterial hypertension and NYHA Class III symptoms. The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

Remodulin : o Indicated as a continuous subcutaneous infusion or intravenous infusion (for those not able to tolerate a subcutaneous infusion) for the treatment of pulmonary arterial hypertension in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. o Indicated in patients with pulmonary arterial hypertension requiring transition from Flolan. Remodulin is indicated to diminish the rate of clinical deterioration. Ventavis : Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in patients with NYHA Class III or IV symptoms. DOSAGE AND ADMINISTRATION: Adcirca : The recommended dose is 40 mg (two 20 mg tablets) taken once daily with or without food. Dividing the dose (40mg) over the course of the day is not recommended. Letairis : Initiate treatment at 5mg once daily with or without food, and consider increasing the dose to 10mg once daily if 5mg is tolerated. Revatio : The recommended dose is 20mg t.i.d. taken approximately 4-6 hours apart. Treatment with doses higher than 20mg t.i.d. is not recommended. Tracleer : Initial dose 62.5mg b.i.d. for 4 weeks and then increased to a maintenance dose of 125mg b.i.d. Doses above 125mg b.i.d. did not appear to confer additional benefit to offset the increased risk of liver injury. Flolan : Continuous chronic infusion of FLOLAN should be administered through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Chronic infusion of FLOLAN should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established and further increases in the infusion rate are not clinically warranted. Tyvaso : Is dosed in 4 separate, equally spaced treatment session per day, during waking hours. The treatment sessions should be approximately 4 hours apart. Therapy should begin with 3 breaths of Tyvaso (18 mcg of treprostinil), per treatment session, 4 times a day. If 3 breaths are not tolerated, reduce to 1 or 2 breaths and subsequently increase to 3 breaths as tolerated. Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated, until the target dose of 9 breaths (54 mcg of treprostinil) is reached per treatment session. If adverse effects preclude titration to target dose, Tyvaso should be continued at the highest tolerated dose. Remodulin : The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min. The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks of treatment and then 2.5 ng/kg/min per week for the remaining duration of infusion, depending on clinical response. There is little experience with doses > 40 ng/kg/min. Ventavis : Ventavis is intended to be inhaled using either of two pulmonary drug delivery devices: the I-neb AAD System or the Prodose AAD System. The first inhaled dose should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5.0 mcg and maintained at that dose, otherwise maintain the dose at 2.5 mcg. Ventavis should be taken 6 to 9 times per day (no more than once every 2 hours) during waking hours, according to individual need and tolerability. The maximum daily dose evaluated in clinical studies was 45 mcg (5 mcg 9 times per day). REFERENCES: 1. Adcirca Prescribing Information. Eli Lilly and Company. February 2011. 2. Tracleer Prescribing Information. Actelion Pharmaceuticals US, Inc. August 2009. 3. Revatio Prescribing Information. Pfizer Labs. November 2010. 4. Letairis Prescribing Information. Gilead Sciences, Inc. October 2010. 5. Flolan Prescribing Information. GlaxoSmithKline. January 2008. 6. Remodulin Prescribing Information. Baxter Pharmaceutical Solutions LLC. February 2011. 7. Tyvaso Prescribing Information. United Therapeutics Corp. February 2011. 8. Ventavis Prescribing Information. Cotherix, Inc. June 2010. 9. Badesch DB, Abman SH, Simonneau G, et al. Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence- Based Clinical Practice Guidelines. Chest 2007; 131: 1917-1928. 10. Humbert M, Sitbon O, Simonneau G. Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2004; 351:1425-36.

11. Nauser TD, Stites SW. Diagnosis and Treatment of Pulmonary Hypertension. Am Fam Physician 2001; 63: 1789-98, 1800. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

SOUTH REGION PRIOR AUTHORIZATION CRITERIA RAPAMUNE (sirolimus) Requires PA Solution: 1mg/mL Tablet: 0.5mg, 1mg, 2mg, 1mg/mL STATUS PA CRITERIA FOR APPROVAL For the prophylaxis of organ rejection in patients 13 years and older who are receiving renal transplants. AND Patient must be 13 years of age and older. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred for medical necessity review. FDA INDICATIONS Renal Transplantaion DOSAGE AND ADMINISTRATION High immunologic risk: Maximum dose: 40 mg/day. Loading dose: Up to 15 mg for patients weighing 40 kg or more and 3 mg/m 2 for patients weighing less than 40 kg on day 1 post transplantation. Maintenance dosage: 5 mg/day for patients weighing 40 kg or more and 1 mg/m 2 /day for patients weighing less than 40 kg beginning on day 2. A trough level should be obtained between days 5 and 7, and the daily dose of sirolimus should be adjusted thereafter. Dosage adjustment: Frequent dosage adjustments based on non steady-state sirolimus concentrations can lead to overdosing or underdosing because sirolimus has a long half-life. Once the maintenance dosage is adjusted, patients should continue on the new maintenance dosage for at least 7 to 14 days before further dosage adjustment with concentration monitoring. In most patients, dosage adjustments can be based on a simple proportion: new dose = current dose (target concentration/current concentration). A loading dose should be considered in addition to a new maintenance dosage when it is necessary to increase sirolimus trough concentrations: sirolimus loading dose = 3 (new maintenance dose current maintenance dose). If an estimated daily dose exceeds 40 mg because of the addition of a loading dose, the loading dose should be administered over 2 days. Concomitant therapy: Use in combination with cyclosporine and corticosteroids for the first 12 months following transplantation. The starting dosage of cyclosporine should be up to 7 mg/kg/day in divided doses and the dosage should subsequently be adjusted to achieve target whole blood trough concentrations. Prednisone should be administered at a minimum of 5 mg/day. Antibody induction therapy may be used. The safety and efficacy of this combination in patients with high immunologic risk have not been studied beyond the first 12 months. Therefore, after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient. Low to Moderate immunologic risk: Maximum dose: 40 mg/day. Loading dose: 6 mg for patients weighing 40 kg or more; and 3 mg/m 2 for patients weighing less than 40 kg. A loading dose of sirolimus equivalent to 3 times the maintenance dose should be given (ie, a daily maintenance dose of 2 mg should be preceded with a loading dose of 6 mg). Maintenance dosage: 2 mg/day for patients weighing 40 kg or more; 1 mg/m 2 for patients weighing less than 40 kg. Dosage adjustment: Frequent dosage adjustments based on non steady-state sirolimus concentrations can lead to overdosing or underdosing because sirolimus has a long half-life. Once the maintenance dosage is adjusted, patients should continue on the new maintenance dosage for at least 7 to 14 days before further dosage adjustment with concentration monitoring. In most patients, dosage adjustments can be based on a simple proportion: new dose = current dose (target concentration/current concentration). A loading dose should be considered in addition to a new maintenance dosage when it is necessary to increase sirolimus trough concentrations: sirolimus loading dose = 3 (new maintenance dose current maintenance dose). If an estimated daily dose exceeds 40 mg because of the addition of a loading dose, the loading dose should be administered over 2 days.

Concomitant therapy: It is recommended that sirolimus be used initially in a regimen with cyclosporine and corticosteroids. At 2 to 4 months following transplantation, cyclosporine should be progressively discontinued over 4 to 8 weeks, and the sirolimus dose should be adjusted to obtain whole blood trough concentrations within the target range. Because cyclosporine inhibits the metabolism and transport of sirolimus, sirolimus concentrations may decrease when cyclosporine is discontinued unless the sirolimus dose is increased. REFERENCES 1. Facts and Comparisons, St. Louis, 2013 efacts CliniSphere Version ISBN 1-57439-036-8. 2. Rapamune. Prescribing Information. Wyeth Pharmaceuticals, Inc. December 2012. Revision/Review Date: 7/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA RITUXAN (rituximab): 10 mg/ml in 10 and 50ml vials PA CRITERIA FOR APPROVAL FOR USE IN RHEUMATOID ARTHRITIS: The medication is being recommended and prescribed by a rheumatologist. The patient is an adult ( 18 y/o) and has a documented clinical diagnosis of rheumatoid arthritis. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) of 3 months or more of therapy) of methotrexate AND then leflunomide (generic Arava ) and/or another disease-modifying antirheumatic treatment option (i.e. combination therapy - methotrexate + sulfasalazine and/or hydroxychloroquine) or has another documented medical reason (e.g. intolerance, hypersensitivity) for not utilizing any of these therapies to manage their medical condition. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses) of etanercept (Enbrel ) AND infliximab (Remicade ) and/or has another medical reason (intolerance, hypersensitivity, etc) for not taking any of these therapies to manage their medical condition. Documentation indicating that Rituxan is being used concurrently with methotrexate. Rituxan is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 1 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN RHEUMATOID ARTHRITIS The member has been receiving Rituxan and documentation is provided that a rheumatologist has reevaluated the member and recommends continuation of therapy. Documentation was provided indicating that the patient had clinical benefit from receiving Rituxan therapy. At least 16 weeks (4 months) has elapsed since the previous course of Rituxan therapy. Documentation indicating that Rituxan is being used concurrently with methotrexate. Rituxan is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 1 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL APPROVAL FOR USE IN NON-HODGKIN S LYMPHOMA (NHL) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): The medication is being recommended and prescribed by an oncologist. If the medication request is for Non-Hodgkin Lymphoma, documentation must be submitted that the patient has CD20-positive B-cell NHL (from a Hematopathology review of all the patient s slides with at least on paraffin block representative of the tumor, lymph node diagnosis and/or bone marrow biopsy with cell surface marker analysis by flow cytometry) If the medication request is for Chronic Lymphocytic Leukemia, documentation that the patient has CD20-positive CLL and Rituxan is being using in concurrently with fludarabine and cyclophosphamide (FC) Rituxan is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 3 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN NON-HODGKIN S LYMPHOMA (NHL) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): The medication is being recommended and prescribed by an oncologist. Rituxan is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 3 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL APPROVAL FOR USE IN GRANULOMATOSIS WITH POLYANGIITIS (GPA) (WEGENER S GRANULOMATOSIS) AND MICROSCOPIC POLYANGIITIS (MPA): The medication is being recommended and prescribed by a rheumatologist. The patient is an adult ( 18 y/o) and has a documented clinical diagnosis of granulomatosis with polyangiitis (GPA) (Wegener s Granulomatosis) or microscopic polyangiitis (MPA).

The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses) of glcocorticod (ie prednisone) AND cyclophosphamide (Cytotoxan ) followed by methotrexate (Trexall ) and/or has another medical reason (intolerance, hypersensitivity, etc) for not taking any of these therapies to manage their medical condition. Documentation indicating that Rituxan is being used concurrently with glucocorticoids. Rituxan is being prescribed at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 1 month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (Micromedex, American Hospital Formulary Service (AHFS), DrugPoints, Drug Package Insert) as defined in the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. The medication is recommended and prescribed a specialist in the field to treat the member s respective medical condition. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (e.g. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). If all of the above conditions are met, the request will be approved for up to a 3 month duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS Documentation that the medication is recommended or prescribed by a specialist for the respective treated disease state and is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, American Hospital Formulary Service (AHFS), DrugPoints, Drug Package Insert) as defined in the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO) or the American Academy of Pediatrics (AAP) standard of care guidelines. Documentation from medical chart was submitted indicating that the member has significantly clinically benefited from the medication. If all of the above conditions are met, the request will be approved for up to a 3 month-week duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATIONS: Rheumatoid arthritis (RA): In combination with methotrexate for the treatment of adult patients with moderately to severely active RA who have had inadequate response to 1 or more tumor necrosis factor (TNF) antagonist therapies Non-Hodgkin s Lymphoma (NHL): Indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-Cell, NHL as a single agent. Indicated for previously untreated follicular CD20-positive, B-cell NHL in combination with first line chemotherapy, as single-agent therapy. Indicated for non-progressing (including stable disease), low-grade, CD-20 positive, B-cell NHL, as a single agent, after first-line treatment with CVP chemotherapy. Indicated for previously untreated diffuse large B-cell CD20 positive, NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or other anathracycline-based chemotherapy regimens. Chronic Lymphocytic Leukemia (CLL): In combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL Granulomatosis with Polyangiitis (GPA) (Wegener s Granulomatosis) and Microscopic Polyangiitis (MPA): In combination with glucorticoids, for the treatment of adult patients with GPA and MPA NON-FDA MEDICALLY ACCEPTED INDICATIONS: Marginal zone lymphoma, gastric MALT lymphoma, non-gastric MALT lymphoma, splenic marginal zone lymphoma, mantle cell lymphoma, Burkitt s lymphoma, lymphoblastic lymphoma, AIDS-related B-cell lymphoma, autoimmune hemolytic anemia, chronic lymphoid leukemia (first line, relapsed or refractory), graft-versus-host disease (chronic steroid-refractory), Waldenstrom s macroglobulinemia, treatment of systemic autoimmune diseases (other than rheumatoid arthritis), immune or idiopathic thrombocytopenic purpura and polymorphic posttransplantation lymphoproliferative disorder. This is not a comprehensive list as updated medical evidence is continually being published.

DOSAGE AND ADMINISTRATION: Rituxan should not be administered as an intravenous push or bolus. Adult Patients with Rheumatoid Arthritis 1000 mg IV followed by a second 1000 mg IV dose 2 weeks later, used in combination with methotrexate. Premedication: administer a glucocorticoid 30 minutes prior to each infusion (such as methylprednisolone 100 mg IV or its equivalent). Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Adult Patients with Diffuse Large B-Cell, CD20-positive NHL : 375 mg/m² IV infusion administered on day 1 of each chemotherapy cycle for up to 8 cycles. Adult Patients with NHL, receiving Rituxan: as a component of Zevalin ( ibritumomab tiuxetan) therapeutic regimen: 250 mg/m² IV infusion within 4 hr prior to administration of indium-111 ibritumomab tiuxetan, then again 7-9 days later within 4 hr prior to administration of yttrium-90 ibritumomab tiuxetan. Adult Patients with Relapsed or Refractory, Low-grade or Follicular, CD20-positive, B-cell NHL: 375 mg/m² IV infusion administered once weekly for 4 or 8 doses. Rituxan may be administered for retreat once weekly for an additional 4 doses. Adult Patients with Previously Untreated, Follicular, CD20-positive, B-cell NHL: 375 mg/m² IV infusion administered on day 1 of each CVP chemotherapy cycle for up to 8 cycles. In patients with complete or partial response, initiate Rituxan maintenance 8 weeks following completion of Rituxan in combination with chemotherapy. Administer Rituxan as a single-agent every 8 weeks for 12 doses. Non-progressing, Low-Grade, CD20-Positive, B-cell NHL after treatment with CVP chemotherapy: 375 mg/m 2 IV infusion once weekly for 4 doses at 6-month intervals for a maximum of 16 doses. Chronic Lymphocytic Leukemia (CLL): 375mg/m 2 IV infusion administered the day prior to the initiation of FC chemotherapy, then 500mg/m 2 on Day 1 of cycles 2-6 (every 28 days) Granulomatosis with Polyangiitis (GPA) (Wegener s Granulomatosis) and Microscopic Polyangiitis (MPA): 375mg/m 2 IV infusion once weekly for 4 weeks, administer with a glucocorticoid (such as methylprednisolone 100mg IV or its equivalent) per day for 1 to 3 days followed by oral prednisone 1mg/kg/day (not to exceed 80mg/day and taper per clinical need) to treat severe vasculitis symptoms. This regimen should begin 14 days prior to or with the initiation of Rituxan and may contine during and after the 4 weeks course of Rituxan treatment. REFERENCE: 1. Emery P, Fleischmann R, Filipowicz-Sosnowska A, et. al. The Efficacy and Safety of Rituximab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Treatment: Results of a Phase IIb Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial. Arthritis & Rheumatism; 2006 54(5): 1390-1400. 2. Bokarewa M, Lindholm C, Zendjanchi K, et. al. Efficacy of Anti-CD20 Treatment in Patients with Rheumatoid Arthritis Resistant to a Combination of Methotrexate/Anti-TNF Therapy. Scandinavian Journal of Immunology 2007; 66: 476-83. 3. Rituxan Prescribing Information. Genentech Pharmaceutical, 05/2013. NCCN Clinical Practice Guidelines in Oncology TM. Hodgkin Lymphoma; V 2.2013. 4. NCCN Clinical Practice Guidelines in Oncology TM. Acute Lymphoblastic Leukemia. V 1.2013. 5. NCCN Clinical Practice Guidelines in Oncology : Non-Hodgkin s Lymphomas;. V 1.2013. 6. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for Rheumatoid Arthritis Refractory to Anti-Tumor Necrosis Factor Therapy: Results of a Multicenter Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating Primary Efficacy and Safety at Twenty-Four Weeks. Arthritis & Rheumatism; 2006 54(9): 2793-2806. Revision/Review Date: 01/2014 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA RESTASIS (cyclosporine) Ophthalmic emulsion: 0.05% FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Diagnosis of dry eye syndrome (decreased tear production) whose lack of tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. AND Diagnosis and prescription by an ophthalmologist or rheumatologists. AND Documented trial and failure or intolerance to a therapeutic trial of artificial tear therapy for a period of 3 months. If the above conditions are met, the request will be approved with a one month supply of medication with up to a 6 month authorization; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Tear production: To increase tear production in patients whose tear production is presumed to be suppressed because of ocular inflammation associated with keratoconjunctivitis sicca. DOSAGE AND ADMINISTRATION: Instill 1 drop twice daily in each eye approximately 12 hours apart. Restasis can be used concomitantly with artificial tears, allowing a 15 minute interval between products. Discard vial immediately after use. REFERENCES: 1. Restasis Prescribing Information. Allergan. February 2010. 2. Kunert KS, et al. Analysis of Topical Cyclosporine Treatment of Patients with Dry Eye Syndrome. Arch Opthalmol. 2000:118:1489-1496 3. Pflugfelger SC. Anti-inflammatory Therapy of Dry Eye. The Ocular Surface; 2003;1:31-36 4. Akpek EK, et al. A randomized trial of topical cyclosporine 0.05% in topical steroid resistant atopic keratoconjunctivitis. Ophthalmology. 2004; 111 (3):476-482 5. Facts and Comparisons, St. Louis, efacts 2011 CliniSphere Version ISBN 1-57439-036-8 Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA RETIN-A (tretinoin) Cream: 0.025%, 0.05%, 0.1%; Gel: 0.01%, 0.025% FORMULARY STATUS: Formulary (generic) PA CRITERIA FOR APPROVAL: Diagnosis of acne vulgaris in patients 21 years of age or older (patients less than 21 years, an automatic approval at the point of service for generic medication will process). If the above conditions are met, the request will be approved with a up to a 6 month duration with generic tretinoin; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Acne: Topical treatment of acne vulgaris. DOSAGE AND ADMINISTRATION: Acne treatment: Apply once a day before bedtime or in the evening. Cover the entire affected area lightly. Therapeutic results should be seen after 2 to 3 weeks, but may not be optimal until after 6 weeks. Once lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications or other dosage forms. Children >12 years and Adults: Begin therapy with a weaker formulation of tretinoin (0.025% cream or 0.01% gel) and increase the concentration as tolerated; apply once daily before retiring or on alternate days; if stinging or irritation develop, decrease frequency of application. REFERENCES: 1. Webster GF. Topical tretinoin in acne therapy. J Am Acad Dermatol 1998 Aug;39(2 Pt 3):S38-44. 2. Guidelines of Care for Acne Vulgaris. American Acaemy of Dermatology Association. J Am Acad Dermatol. 1990. 22:676-80. 3. Drake, LA et al. Guidelines of care for nevi (nevocellular nevi and sehorrheic keratoses). JAm Acad Derm: April 1992; 26(4): 629-631. 4. Verschoore M. et al. Topical Retinoids. Their Uses in Dermatology. Derm Ther. Jan 1993; 99(I):107-115. 5. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 6. Retin-A Prescribing Information. Ortho Dermatological. February 2001. 7. Winston MH, Shalita AR, Acne Vulgaris, Pathogenesis and Treatment, Pediatr Clin North Am, 1991,38(4):889-903. 8. Lexicomp online. Updated June 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SECOND-GENERATION ANTIHISTAMINES FORMULARY STATUS Formulary, Pays at Point-of-Sale (First Line) ALLEGRA (fexofenadine) Suspension: 30mg/5mL (Only children < 2 years old will pay at point of sale) ZYRTEC OTC (cetirizine) (generic) Tablet: 5mg, 10mg; Syrup: 5mg/5mL ZYRTEC-D 12 HOURS OTC (cetirizine/pseudoephedrine) (generic) Tablet: 5mg/120mg CLARITIN (loratadine) (generic) Tablet: 10mg; RediTab: 5 mg, 10mg; Syrup: 5mg/5mL CLARITIN-D 12 HOUR (loratadine/pseudoephedrine) (generic) Tablet: 5mg/120mg CLARITIN-D 24 HOUR (loratadine/pseudoephedrine) (generic) Tablet: 10mg/240mg FORMULARY STATUS Formulary, Requires Prior Authorization (Second Line) ALLEGRA (fexofenadine) (generic) Tablet: 30mg, 60mg, 180mg ALLEGRA ALLERGY (fexofenadine) Tablet: 60mg, 180mg CHILDREN S ALLEGRA ALLERGY (fexofenadine) Tablet: 30mg, Oral Suspension: 30mg/5m ALLEGRA-D 12 HOUR (fexofenadine/pseudoephedrine) Tablet: 60mg/120mg ALLEGRA-D 24 HOUR (fexofenadine/pseudoephedrine) Tablet: 180mg/240mg ALLEGRA (fexofenadine) Suspension: 30mg/5mL NOTE: Patient must meet #1 & #2 criteria for approval of PA request. FORMULARY STATUS Non-Formulary, Requires Prior Authorization (Third Line) ALLEGRA (fexofenadine) Orally Disintegrating Tablet (ODT): 30mg CHILDREN S ALLEGRA ALLERGY (fexofenadine) Orally Disintegrating Tablet: 30mg CLARINEX (desloratadine) Tablet: 5mg; RediTab: 2.5mg, 5mg; Syrup: 2.5mg/5mL CLARINEX-D 12 HOUR (desloratadine/pseudoephedrine) Tablet: 2.5mg/120mg CLARINEX-D 24 HOUR (desloratadine/pseudoephedrine) Tablet: 5mg/240mg XYZAL (levocetirizine) Tablet: 5mg; Solution: 2.5mg/5ml ZYRTEC OTC (cetirizine) (generic) Chewable Tablet: 5mg, 10mg NOTE: Patient must meet #1, #2, & #3 criteria for approval of PA request. PA CRITERIA FOR APPROVAL: 1. Diagnosis of seasonal allergic rhinitis with or without nasal congestion, perennial allergic rhinitis with or without nasal congestion, or urticaria. 2. Documented trial and failure or intolerance to a first line loratadine AND cetirizine product for at least 4 weeks (28 days) of therapy each within the past 12 months or a minimum of 2 weeks of therapy or intolerance to Claritin-D and Zyrtec-D within the past 12 months. 3. Documented trial and failure or intolerance to fexofenadine for at least 4 weeks (28 days) of therapy in the past 12 months or 2 weeks of therapy or intolerance to Allegra-D within the past 12 months. If the specified conditions are met, the request will be approved with up to a 12-month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: ANTIHISTAMINES Indications Claritin Clarinex Zyrtec Allegra Xyzal Seasonal Allergic Rhinitis X X X X X Perennial Allergic Rhinitis X X X Chronic Idiopathic Urticaria X X X X X

COMBINATION ANTIHISTAMINES-DECONGESTANTS Claritin-D 12 Clarinex-D 12 Zyrtec-D 12 Allegra-D 12 Indications & 24 Hour & 24 Hour Hour & 24 Hour Seasonal Allergic Rhinitis X X X X Perennial Allergic Rhinitis Chronic Idiopathic Urticaria X DOSAGE AND ADMINISTRATION: Claritin Children 2-5 Years: 5mg once daily. Adults and Children 6 Years of Age and Older: 10mg once daily. Claritin-D 12 Hour Adults and Children 12 Years of Age and Older: 1 tablet every 12 hours. Claritin-D 24 Hour Adults and Children 12 Years of Age and Older: 1 tablet once daily. Clarinex Children 6-11 Months: 2mL (1mg) of the syrup once daily. Children 12 Months to 5 Years: ½ teaspoonful (1.25mg) of the syrup once daily. Children 6-11 years: 1 teaspoonful (2.5 mg) of the syrup once daily or one 2.5mg RediTab once daily. Adults and Children 12 Years and Older: 5mg once daily. Clarinex-D 12 Hour Adults and Children 12 Years and Older: 1 tablet twice every 12 hours. Clarinex-D 24 Hour Adults and Children 12 years and Older: 1 tablet once daily. Zyrtec Children 6 Months to <2 Years: 2.5mg (½ teaspoonful) of the syrup once daily. The dose in children 12-23 months of age can be increased to a max of 5mg per day, given as ½ teaspoonful every 12 hours. Syrup is recommended for children under the age of 2 years. Children 2-5 Years: 2.5mg (½ teaspoonful) of the syrup once daily. The dosage in this age group can be increased to a maximum dose of 5mg per day given as 1 teaspoon syrup once a day or ½ teaspoon syrup given every 12 hours, or one 5 mg chewable tablet once daily. Children 6-11 Years: 5mg or 10mg once daily depending on symptom severity. The time of administration may be varied to suit individual patient needs. Adults and Children 12 Years and Older: 5mg or 10mg per day in adults and children 12 years and older, depending on symptom severity. Most patients in clinical trials started at 10mg. Zyrtec is given as a single daily dose. The time of administration may be varied to suit individual patient needs. Zyrtec-D 12 Hour Adults and Children 12 Years of Age and Older: 1 tablet every 12 hours. Allegra Children 6-11 Years: 30mg twice daily. Adults and Children 12 Years and Older: 60mg twice daily or 180mg once daily. Allegra Oral Suspension Children 2-11 Years with Seasonal Allergic Rhinitis: 30mg (5mL) twice daily. Children 2-11 Years with Chronic Idiopathic Urticaria: 30mg (5mL) twice daily. Children 6 Months to <2 Years with Chronic Idiopathic Urticaria: 15mg (2.5mL) twice daily. Allegra-D 12 Hour Adults and Children 12 Years of Age and Older: 1 tablet every 12 hours. Allegra-D 24 Hour Adults and Children 12 years and Older: 1 tablet once daily. Xyzal Children 6 Months to 5 Years: 1.25mg (1/4 tablet) once daily in the evening.

Children 6-11 Years: 2.5mg (½ tablet) once daily in the evening. Adults and Children 12 Years and Older: 5mg once daily in the evening. Some patients may be adequately controlled by 2.5mg (½ tablet) once daily in the evening. Xyzal Solution Children 6 Months to 5 Years: 2.5mL (1.25mg) once daily in the evening. Children 6-11 Years: 5mL (2.5mg) once daily in the evening. Adults and Children 12 Years and Older: 10mL (5mg) once daily in the evening. Some patients may be adequately controlled by 2.5mg (½ tablet) once daily in the evening. REFERENCES: 1. Allegra. Prescribing Information. Sanofi-Aventis. December 2009. 2. Allegra-D 12 Hour. Prescribing Information. Sanofi-Aventis. December 2009. 3. Allegra-D 24 Hour. Prescribing Information. Sanofi-Aventis. December 2009. 4. Clarinex. Prescribing Information. Schering Corporation. December 2010. 5. Clarinex-D 12 Hour. Prescribing Information. Schering Corporation. December 2009. 6. Clarinex-D 24 Hour. Prescribing Information. Schering Corporation. December 2009. 7. Claritin. Prescribing Information. Available from: http://www.claritin.com/claritin/hcp/index.jspa. Accessed August 2011. 8. Xyzal. Prescribing Information. UCB, Inc. December 2010. 9. Zyrtec. Prescribing Information. Available from: http://www.zyrtecprofessional.com/index.html. Accessed August 2011. 10. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8. 11. Allegra OTC. Information for healthcare professionals. Available from: http://www.allegra.com/hcp. Accessed August 2011. Revision/Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SEDATIVE HYPNOTICS FORMULARY STATUS Formulary (generic), Pays at Point-of-Sale (First Line) AMBIEN (zolpidem) Tablet: 5mg, 10mg SONATA (zaleplon) Capsule: 5mg, 10mg FORMULARY STATUS Formulary, Requires Step Therapy (Second Line) ROZEREM (ramelteon) Tablet: 8mg NOTE: Patient must meet criteria #1 & #2 for approval of initial PA request. FORMULARY STATUS Non-Formulary, Requires Prior Authorization (Third Line) AMBIEN CR (zolpidem extended-release) Tablet: 6.25mg, 12.5mg EDLUAR (zolpidem) Sublingual Tablet: 5mg, 10mg LUNESTA (eszopiclone) Tablet: 1mg, 2mg, 3mg NOTE: Patient must meet criteria #1, #2 & #3 for approval of initial PA request. PA CRITERIA FOR APPROVAL: 1. Diagnosis of insomnia. 2. Documented trial and failure or intolerance to Ambien (zolpidem) or Sonata (zaleplon) for at least 2 weeks (14 days) of therapy. 3. Documented trial and failure or intolerance to Rozerem for at least 2 weeks (14 days) of therapy. NOTE: Rozerem can be approved as a first line agent if there is a history of substance abuse. If the above conditions are met, the initial request will be approved with a 6 month duration with generic medication. If the above conditions are not met, the request will be referred to a psychiatrist for medical necessity review. NOTE: Renewal requests are approvable for up to a 12 month duration. FDA INDICATIONS: Ambien: Short-term treatment of insomnia characterized by difficulties with sleep initiation. Ambien CR: Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). Edluar: Short-term treatment of insomnia characterized by difficulties with sleep initiation. Lunesta: Treatment of insomnia. Rozerem: Treatment of insomnia characterized by difficulty with sleep onset. Sonata: Short-term treatment of insomnia. DOSAGE AND ADMINISTRATION: Ambien: The recommended dose for adults is 10mg immediately before bedtime. For certain individuals, 5mg may be a sufficient dose. Ambien CR: The recommended dose for adults is 12.5mg immediately before bedtime. For certain individuals, 6.25mg may be a sufficient dose. Edluar: The recommended dose for adults is 10mg once daily immediately before bedtime. For the elderly, debilitated patients, and patients with hepatic impairment, the recommended dose is 5mg once daily immediately before bedtime. Edluar sublingual tablet should be placed under the tongue, where it will disintegrate. The tablet should not be swallowed and the tablet should not be taken with water. Edluar should not be administered with or immediately after a meal. Lunesta: The recommended starting dose for Lunesta for most non-elderly adults is 2 mg immediately before bedtime. Dosing can be initiated at or raised to 3mg if clinically indicated, since 3mg is more effective for sleep maintenance. The recommended starting dose of Lunesta for elderly patients whose primary complaint is difficulty falling asleep is 1mg immediately before bedtime. In these patients, the dose may be increased to 2mg if clinically indicated. For elderly patients whose primary complaint is difficulty staying asleep, the recommended dose is 2mg immediately before bedtime. Rozerem: The recommended dose is 8mg taken within 30 minutes of going to bed. Sonata: The recommended dose for adults is 10mg immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep. For certain individuals, 5mg may be a sufficient dose. REFERENCES: 1. Ambien. Prescribing Information. Sanofi-Aventis. August 2010. 2. Ambien CR. Prescribing Information. Sanofi-Aventis. October 2010 3. Edluar. Prescribing Information. Meda Pharmaceuticals. July 2009. 4. Lunesta. Prescribing Information. Sepracor, Inc. July 2011. 5. Rozerem. Prescribing Information. Takeda Pharmaceuticals America, Inc. November 2010. 6. Sonata. Prescribing Information. Wyeth Pharmaceuticals, Inc. February 2009. 7. Facts and Comparisons, St. Louis 2011 efacts CliniSphere Version ISBN 1-57439-036-8. Review Date: 7/2012

Associated Policy: Prior Authorization of Medications 236.200 NOTE: Psychiatrist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SEROSTIM (somatropin): 4-mg vial, 5-mg vial, 6-mg vial, 8.8mg vial and cartridge Formulary Status: Non-formulary PA CRITERIA FOR INITIAL APPROVAL FOR HIV RELATED WASTING OR CACHEXIA: The patient is an adult ( 18 y/o) and has a documented clinical diagnosis of human immunodeficiency virus (HIV). The patient is receiving optimal highly active antiretroviral therapy (HAART) as documented by a recent (with in past 2 months) infectious disease specialist consultation or by recent (with in past 2 months) laboratory blood analysis indicating plasma HIV RNA of less than 50 copies/ml Documentation was submitted that indicates that the member does not have cancer (excluding Kaposi s sarcoma & Lymphoma) Documentation was submitted that indicates that the member does not have any psychiatric disorders, such as anxiety and depression, or documentation was submitted that the member is receiving treatment for a psychiatric disorder Documentation was submitted that indicates that the member does not have any active opportunistic infections (thrush, MAC), diarrhea and GI infections, or that if they have any of these conditions it is clinically resolved and stabilized with treatment For male patients, laboratory values were submitted indicating testosterone levels are within normal limits, or that the patient is receiving testosterone supplementation and documentation was submitted indicated testosterone levels are within normal limits The patient is receiving documented nutritional support The results of a recent (within 30 days) Body Impedance Analysis (BIA) has been submitted for review and meets at least one of the following criteria associated with AIDS wasting based on Body Impedance Analysis (BIA): unintentional weight loss of 7.5% over the past 6 months (for patients with a BMI less than 25), in men: BCM < 35% of total BW and BMI < 27 kg/m 2, in women: BCM < 23% of total BW and BMI < 27 kg/m 2, or BMI < 20 kg/m 2 *** For BCMs 33 and 34 if patient weight is normal per height and weight charts, require at least 2 BIA analysis to confirm trend. There can be 10% or more error with analysis. If only one BIA with BCM 33-34 refer to medical director. *** The patient has tried a 2 month or more course of therapy with megestrol acetate, dronabinol or cyproheptadine for appetite stimulation in the past 2 months or has a documented medical reason for not taking megestrol acetate, dronabinol or cyproheptadine. The patient has tried a 2 month course of therapy with anabolic steroids (e.g. Nandrolone, Oxandrin or Winstrol) in the past 2 months or has a medical reason for not taking an anabolic steroid. If all of the above conditions are met, the request will be approved with a 4-week duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-APPROVAL FOR HIV RELATED WASTING OR CACHEXIA: Documentation was sent in at the end of 4 weeks of a repeat BIA analysis that shows the patient s lean body mass has stabilized or improved Duration of therapy does not exceed 12 weeks If the last trial of Serostim was in the distant past and was successful, then evaluate the patient as naïve If all of the above conditions are met, the request will be approved for an additional 8-week duration (12 weeks total); if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL APPROVAL FOR HIV RELATED LIPODYSTROPHY or HIV ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME: The patient is an adult ( 18 y/o) and has a documented clinical diagnosis of HIV. Documentation that the patient does not have diabetes mellitus and is not receiving any insulin or insulin-sensitizing agents. Documentation that the patient is compliant with an unchanged HAART for at least 3 months prior to the initiation of therapy. Documentation was submitted that indicates that the member does not have an active infection or malignancy (excludes patients with less than five cutaneous Kaposi s sarcoma lesions). Documentation that the patient does not have untreated or uncontrolled hypertension (i.e. blood pressure > 140/90 mm Hg).

A letter of medically necessity documenting the evidence of HIV related lipodystrophy. The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or per the standard of care guidelines. If all of the above conditions are met, the request will be approved with a 12-week duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-APPROVAL FOR HIV RELATED LIPODYSTROPHY or HIV ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME: Duration of therapy does not exceed 9 months. The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment. The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or per the standard of care guidelines. If all of the above conditions are met, the request will be approved with a 24-week duration (9 months total); if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or the standard of care guidelines. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines or has another documented medical reason (i.e. intolerance, contraindications) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act or per the standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints and AHFS drug information) as defined by the Social Security Act or per the NCCN or ASCO standard of care guidelines. The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, or per recommendations of the medical compendium as described above, or per the standard of care guidelines. If all of the above conditions are met, the request will be approved for up to a 12-week duration. If all of the above criteria are not met, the request is referred to a Medical Director for medical. FDA INDICATION: Serostim is indicated for the treatment of AIDS wasting or cachexia. MEDICALLY ACCEPTED INDICATIONS: HIV-associated adipose redistribution (e.g. HIV-related lipodystrophy)

DOSAGE AND ADMINISTRATION for HIV RELATED WASTING OR CACHEXIA: Weight Range Dose >55 kg (>121 lb) 6 mg SC daily 45-55 kg (99-121 lb) 5 mg SC daily 35-45 kg (75-99 lb) 4 mg SC daily <35 kg (< 75 lb) 0.1 mg/kg SC daily Based on an approximate daily dosage of 0.1 mg/kg DOSAGE AND ADMINISTRATION FOR HIV RELATED LIPODYSTROPHY or HIV ASSOCIATED ADIPOSE REDISTRIBUTION SYNDROME: 4 mg SC daily 4 mg SC every other day 2 mg SC every other day REFERENCES: 1. HIV Fitness guidelines: Body composition. Available from: www.hivfitness.org 12/20/01. 2. Steinhart CR. HIV-Associated Wasting in the Era of HAART: A Practice-Based Approach to Diagnosis and Treatment. The AIDS Reader 2001; 11:566-569. 3. Bickel M, Zangos S, Jacobi V, et al. A randomized, open-label study to compare the effects of two different doss of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy. HIV Medicine 2006; 7: 397-403. 4. Grunfeld C, Thompson M, Brown S, et al. Recombinant Human Growth Hormone to Treat HIV- Associated Adipose Redistribution Syndrome: 12-week Induction and 24-Week Maintenance Therapy. J Acquir Immune Defic Syndrome 5. Serostim, EMD Serono, Inc., package insert information July 2007. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician review must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SEROTONIN RECEPTOR AGONISTS (TRIPTANS) STATUS Preferred, Pays at Point-of-Sale IMITREX (sumatriptan) Tablet: 25mg, 50mg, 100mg; Nasal Spray: 5mg, 20mg; Subcutaneous Injection: 4mg/0.5mL, 6mg/0.5mL MAXALT (rizatriptan) Tablet: 5mg, 10mg MAXALT-MLT (rizatriptan) Orally Disintegrating Tablet: 5mg, 10mg STATUS Non-Preferred, Requires Prior Authorization AMERGE (naratriptan) Tablet: 1mg, 2.5mg AXERT (almotriptan) Tablet: 6.25mg, 12.5mg FROVA (frovatriptan) Tablet: 2.5mg RELPAX (eletriptan) Tablet: 20mg, 40mg TREXIMET (sumatriptan/naproxen) Tablet: 85mg/500mg ZOMIG (zolmitriptan) Tablet: 2.5mg, 5mg; Nasal Spray: 5mg ZOMIG-ZMT (zolmitriptan) Orally Disintegrating Tablet: 2.5mg, 5mg PA CRITERIA FOR APPROVAL Imitrex: Diagnosis of migraine headaches. Diagnosis of cluster headaches (Imitrex injection only). An automatic approval at the point-of-sale will occur if the quantities prescribed do not exceed 12 tablets per 30 days, 6 nasal spray units per 30 days, and 4 injections per 30 days. Non-Preferred Agents (Excluding Treximet): Diagnosis of migraine headaches. Documented trial and failure or intolerance to Imitrex and Maxalt/Maxalt MLT If the above conditions are met, the request will be approved with a 12 month duration with a quantity not to exceed 12 tablets per 30 days and 6 nasal spray units per 30 days; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. Treximet: Requests for Treximet should be directed to using the two individual agents (sumatriptan and naproxen). Quantities Greater than Allowed per 30 days if Prior Authorization Criteria Met: If the patient requires doses greater than the set limits above after meeting approval, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS Serotonin receptor agonists are indicated for the acute treatment of migraine attacks with or without aura in adults. They are not indicated for prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Imitrex injection is also indicated for treatment of cluster headache episodes in adults. DOSAGE AND ADMINISTRATION Amerge: Tablet: 1 or 2.5mg at onset; may repeat after 4 hours. Do not to exceed 5mg in a 24 hour period. Axert: Tablet 6.25 or 12.5mg at onset; may repeat after 2 hours. Do not exceed 2 doses in a 24 hour period. Maximum daily dose 25 mg. Frova: Tablet 2.5mg at onset; may repeat after 2 hours. Do not exceed 7.5mg in a 24 hour period. Imitrex: Tablet: 25, 50 or 100mg at onset; may repeat after 2 hours. Do not exceed 200mg in a 24 hour period. Nasal Spray: 5, 10 (5 mg dose in each nostril) or 20mg (1 spray) at onset; may repeat after 2 hours. Do not exceed 40mg in a 24 hour period.

Subcutaneous Injection: 4 or 6mg subcutaneously at onset; may repeat in 1 hour. Do not exceed 6mg/dose and 12mg in a 24 hour period. Maxalt: Tablet: 5 or 10mg at onset; may repeat after 2 hours. Do not exceed 30mg in a 24 hour period. Orally Disintegrating Tablet: 5 or 10mg at onset; may repeat after 2 hours. Do not exceed 30mg in a 24 hour period. Pediatric patients 6 to 17 years: 5mg single dose in patients <40kg; 10mg single dose in patients 40kg Relpax: Tablet: 20 or 40mg at onset; may repeat after 2 hours. Do not exceed a 40mg/dose or 80mg in a 24 hour period. Treximet: Tablet: 85mg/500mg at onset; may repeat after 2 hours. Do not exceed 170mg/1000mg in a 24 hour period. Zomig: Tablet: 2.5 or 5mg at onset; may repeat after 2 hours. Do not exceed 10mg in a 24 hour period. Orally Disintegrating Tablet: 2.5 or 5mg at onset; may repeat after 2 hours. Do not exceed 10mg in a 24 hour period. Nasal Spray: 5mg (1 spray) at onset; may repeat after 2 hours. Do not exceed 10mg in a 24 hour period. REFERENCES 1. Amerge. Prescribing Information. GlaxoSmithKline. February 2010. 2. Axert. Prescribing Information. Ortho-McNeil Pharmaceuticals. September 2011. 3. Frova. Prescribing Information. Endo Pharmaceuticals, Inc. April 2007. 4. Imitrex (Tablets and Nasal Spray). Prescribing Information. GlaxoSmithKline. February 2010. 5. Imitrex (Subcutaneous Injection) Prescribing Information. GlaxoSmithKline. February 2010. 6. Maxalt and Maxalt-MLT. Prescribing Information. Merck & Co., Inc. December 2011. 7. Relpax. Prescribing Information. Pfizer. April 2011. 8. Treximet. Prescribing Information. GlaxoSmithKline. December 2011. 9. Zomig, Zomig-ZMT and Zomig Nasal Spray. Prescribing Information. AstraZeneca Pharmaceuticals. October 2008. 10. Facts and Comparisons, St. Louis, 2013 efacts CliniSphere Version ISBN 1-57439-036-8. 11. Lexi-Comp Online. Available from: http://online.lexi.com.db.usip.edu/crlonline. Accessed January 2013. 12. Micromedex Online Available from: http://www.thomsonhc.com.db.usip.edu/hcs/librarian. Accessed January 2013. Revision/Review Date: 2/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Pharmacist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SOLIRIS (Eculizumab) 300 single-use vials containing 30 ml of 10 mg/ml sterile, preservative-free solution Formulary Status: Non-formulary PA CRITERIA FOR APPROVAL: The member is an adult (18 y/o or older) and lab documentation (i.e. from flow cytometric confirmation) was submitted confirming the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) type III erythrocyte cells. Documentation from medical chart indicating the member s red blood cell transfusion history from the past 12 months prior to request. Documentation submitted indicates that the member has had multiple transfusions in the past 12 months due to PNH. Documentation was submitted with the following lab results: the last pre-transfusion hemoglobin level, a Lactase dehydrogenase (LDH) level (results taken within 30 days of request) that is 1.5 times upper limit of normal and a PNH type III erythrocyte level proportion of 10% of more(results taken within 30 days of request). Documentation submitted that the member s last pre-transfusion hemoglobin level was less that 10.5 g- dl. Documentation submitted indicates that the patient has been vaccinated with the meningococcal vaccine at least 2 weeks prior to initiation of Soliris therapy and/or revaccinated according to current medical guidelines for vaccine use. The medication is being prescribed by a hematologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. REAUTHORIZATION CRITERIA: For first reauthorization requests: documentation from medical chart was submitted indicating that a hematologist has evaluated the member and recommends continuation of therapy due to submitted clinical/diagnostic documentation that demonstrates that the member has benefited from the medication (e.g. reduced number of red blood cell transfusions, decreased LDH level, improved hemoglobin levels, increase in PNH type III erythrocytes, improved fatigue or quality of life) since beginning therapy with Soliris. For additional reauthorization requests beyond 12 months of therapy: documentation from medical chart was submitted indicating that a hematologist has evaluated the member and recommends continuation of therapy due to the member has remained clinically stable while on Soliris (e.g. red blood cell transfusion requirements have remained the stable or reduced, LDH level remained close to upper limits of normal, hemoglobin levels remaining stable, PNH type III erythrocytes stable or improved, low to no fatigue and continues with improved quality of life) while taking Soliris therapy. Documentation was submitted indicating the date of the member s last meningococcal vaccine. The medication is being prescribed by a hematologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Soliris is indicated for treatment of adult patients (18 y/o or older) with paroxysmal nocturnal hemoglobuinuria (PNH) to reduce hemolysis. DOSAGE AND ADMINISTRATION: Dosage Regimen: 600 mg as an IV infusion over 35 minutes given every 7 days for the first 4 weeks, followed by: 900 mg IV over 35 minutes for the 5 th dose 7 days later then, 900 mg IV over 35 minutes every 14 days thereafter.

REFERENCES: 1. Soliris prescribing information. Alexion Pharmaceuticals, Inc. June 2009. 2. Hillmen P. Young NS. Schubert J. et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. The New England Journal of Medicine. 2006;355:1233-1243. 3. Hill A. Richards SJ. Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. British Journal of Haematology. 2007;137:181-192. 4. Parker C. Omine M. Richards S. et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709. 5. http://www.nlm.nih.gov/medlineplus/ency/article/003471.htm. For Definition of LDH. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgement, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SPORANOX (itraconazole) Capsule: 100mg; Oral Solution: 10mg/mL STATUS Preferred PA CRITERIA FOR APPROVAL Immunocompromised patient. OR Trial and failure or intolerance to a preferred oral antifungal. OR Following completion of or intolerance to amphotericin B therapy. OR Diagnosis of aspergillosis. If any of the above conditions are met, the request will be approved with a 3 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS Sporanox Capsules: Indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary. Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis. Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium). Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Sporanox Oral Solution: Empiric therapy of febrile neutropenic patients with suspected fungal infections. In a comparative trial, the overall response rate for itraconazole-treated subjects was higher than for amphotericin B-treated subjects. However, compared to amphotericin B-treated subjects, a larger number of itraconazole-treated subjects discontinued treatment due to persistent fever and a change in antifungal medication due to fever. Whereas, a larger number of amphotericin B-treated subjects discontinued due to drug intolerance. Treatment of oropharyngeal and esophageal candidiasis. DOSAGE AND ADMINISTRATION Sporanox Capsules: Blastomycosis and Histoplasmosis: 200mg (2 capsules) once daily. If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100mg increments to a maximum of 400mg daily. Doses above 200mg/day should be given in two divided doses. Aspergillosis: 200-400mg daily. Onychomycosis of the Toenails with or without Fingernail Involvement: 200mg (2 capsules) once daily for 12 consecutive weeks. Onychomycosis of the Fingernails only: Two treatment pulses, each consisting of 200mg (2 capsules) twice daily (400mg/day) for 1 week. The pulses are separated by a 3 week period without Sporanox. ***Sporanox Capsules should be taken with a full meal to ensure maximal absorption. ***Sporanox Capsules is a different preparation than Sporanox Oral Solution and should not be used interchangeably. Sporanox Oral Solution: Treatment of Oropharyngeal and Esophageal Candidiasis: The solution should be vigorously swished in the mouth (10mL at a time) for several seconds and swallowed. The recommended dosage of Sporanox Oral Solution for oropharyngeal candidiasis is 200mg (20mL) daily for 1 to 2 weeks. Clinical signs and symptoms of oropharyngeal candidiasis generally resolve within several days. For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose is 100mg (10mL) twice

daily. For patients responding to therapy, clinical response will be seen in 2 to 4 weeks. Patients may be expected to relapse shortly after discontinuing therapy. Limited data on the safety of long-term use (>6 months) of Sporanox Oral Solution are available at this time. The recommended dosage of Sporanox Oral Solution for esophageal candidiasis is 100mg (10mL) daily for a minimum treatment of three weeks. Treatment should continue for 2 weeks following resolution of symptoms. Doses up to 200mg (20mL) per day may be 64 used based on medical judgment of the patient s response to therapy. Only Sporanox Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis. ***Sporanox Oral Solution should be taken with a full meal to ensure maximal absorption. ***Sporanox Oral Solution is a different preparation than Sporanox Capsules and should not be used interchangeably. REFERENCES 1. Sporanox Capsules. Prescribing Information. PriCara. March 2009. 2. Sporanox Oral Solution. Prescribing Information. Janssen Pharmaceutica. March 2009. 3. Facts and Comparisons, St. Louis, 2012 efacts CliniSphere Version ISBN 1-57439-036-8. 4. FDA Drug Discontinuations. Sporanox (Itraconazole) Injection. Available from: http://www.fda.gov/cder/drug/shortages/sporanox-10-11-2007.pdf. Updated 11 October 2007. Accessed 20 December 2007. Revision/Review Date: 2/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA STADOL NS (butorphanol) Nasal Spray: 10mg/ml FORMULARY STATUS: Non-Formulary (generic) PA CRITERIA FOR APPROVAL: PAIN: Diagnosis of pain. AND Documented trial and failure with therapeutic doses or intolerance to at least three oral narcotic medications including: oxycodone, oxycodone/acetaminophen, hydromorphone, hydrocodone/acetaminophen, acetaminophen/codeine, and morphine sulfate (first line therapies). If the above conditions are met, the request will be approved with up to a 3 month duration with generic medication (quantity limit of 1 bottle/30 days); if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. MIGRAINE HEADACHE: Diagnosis of pain from migraine headache. AND Documented trial with therapeutic doses of at least one recommended migraine preventative therapy (topiramate, propranolol, timolol, divalproex sodium, amitriptyline, nortriptyline, and verapamil). AND Documented trial and failure with therapeutic doses or intolerance to abortive therapy including at least one triptan and Migranal (unless contraindicated). AND Documented trial and failure with therapeutic doses or intolerance to at least three oral narcotic medications including: oxycodone, oxycodone/acetaminophen, hydromorphone, hydrocodone/acetaminophen, acetaminophen/codeine, and morphine sulfate. If the above conditions are met, the request will be approved with a up to a 3 month duration of generic medication (quantity limit of 1 bottle/30 days); if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR RENEWAL: Patient currently under the care of a neurologist or pain management specialist. AND Documentation submitted by neurologist or pain management specialist supporting re-evaluation of patient. OR Medical necessity of continued use of medication. If the above conditions are met, the request will be approved with up to a 6 month duration of generic medication (quantity limit of 1 bottle/30 days); if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Management of pain when the use of an opioid analgesic is appropriate. In clinical trials, nasal butorphanol was effective in the treatment of migraine headache pain. DOSAGE AND ADMINISTRATION: 1 mg (1 spray in 1 nostril). If adequate pain relief is not achieved within 60 to 90 minutes, an additional 1 mg dose may be given. The initial 2-dose sequence may be repeated in 3 to 4 hours as needed after the second dose. Depending on the pain severity, an initial 2 mg dose (1 spray in each nostril) may be used in patients who will be able to remain recumbent. Do not give additional 2 mg doses for 3 to 4 hours. Migraine: 1 mg INTRANASALLY (one spray in one nostril), followed by a 2nd dose in 60 minutes Pain: 1 mg INTRANASALLY (one spray in one nostril), followed by 2nd dose in 60 to 90 minutes as needed, repeat every 3 to 4 hr as needed.

WARNING: Drug abuse, dependence, and withdrawal: Because of its opioid antagonist properties, butorphanol is not recommended for use in patients dependent on narcotics. Such patients should have an adequate period of withdrawal from opioid drugs prior to beginning butorphanol therapy. Although butorphanol has low physical dependence liability, exercise care in administering to emotionally unstable patients and to those prone to drug misuse and abuse. Abuse has been reported. Prolonged, continuous use of butorphanol tartrate may result in physical dependence or tolerance. Abrupt cessation of use by patients with physical dependence may result in symptoms of withdrawal. REFERENCES: 1. Matchar DB, Young WB, Rosenberg JH, et al. Evidence based guidelines for the management and prevention of migraine headache in the primary care setting. American Academy of Neurology. September 2000 2. Hoffert MJ; Couch JR; Diamond S; Elkind AH; Goldstein J; Kohlerman NJ; Saper JR; Solomon S. Transnasal butorphanol in the treatment of acute migraine. Headache 1995 Feb;35(2):65-9 3. Elenbaas RM; Iacono CU; Koellner KJ; Pribble JP; Gratton M; Racz G; Evens RP. Dose effectiveness and safety of butorphanol in acute migraine headache. Pharmacotherapy 1991;11(1):56-63 4. Edmeads JG, Gawel MJ, Vickers J. Strategies for diagnosing and managing medication-induced headache. Can Fam Physician. 1997; 43:1249-1254. 5. Mathew NT. Transformed migraine, analgesic rebound, and other chronic daily headaches. Neurologic Clinics. 1997; 15 (1)167-186. 6. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence- based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754-762. 7. Moore KL, Noble SL. Drug treatment of migraine: Part 1. Acute therapy and drug-rebound headache. Am Fam Physician. 1997; 56 (8): 2039-2048. 8. Edmeads J. Headaches in older people. Postgrad Med 1997 101(5): 91-100. 9. Fisher MA, Glass S. Butorphanol (Stadol): A study in problems of current drug information and control JNeurology. 1997:48:1156-1160. 10. Stadol Drug Information. Micromedex 2011 11. Facts and Comparisons, St. Louis, 2011 efacts CliniSphere Version ISBN 1-57439-036-8 12. Butorphanol Tartrate Nasal Spray. Prescribing Information. Apotex Inc. January 2009. 13. Hildreth CJ, Lynm C, Glass RM. Migraine Headache. JAMA 2009;301(24):2608. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA SUBOXONE (buprenorphine HCL/naloxone) Tablet and Film: 2/0.5mg, 8/2mg FORMULARY STATUS: Formulary SUBUTEX (buprenorphine HCL) Tablet: 2mg, 8mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: INITIAL PA: Patient age > or = 16 years old; Physician meets all qualifications to prescribe Suboxone (Federal, State, and Local); Patient is diagnosed with opioid dependence and/or opioid addiction; The risks of using Suboxone with alcohol or benzodiazepines have been explained to the patient; No untreated or unstable psychiatric conditions that would interfere with Suboxone compliance; o No more than one (1) prior attempt to treat opiate addiction with Suboxone within the prior 12 months; Negative pregnancy test (for women, as indicated); Documentation of referral to or active involvement in formal counseling by a licensed behavioral health provider (D&A counselor is preferred, but not required). 12-step program participation, by itself, is not acceptable. If these criteria are met, then an initial maximum of 3 months of Suboxone (1 month dispensed at a time) or up to a total of 4 weeks of Subutex will be authorized, depending upon the request of the physician. If the criteria are not met, psychiatrist review will be necessary to determine whether other factors, such as age, co-morbidities, social situation, or prior treatment considerations, would support medical necessity for the initiation or re-initiation of Suboxone. RENEWAL PA: Consistent use of Suboxone during the prior 3 months, as verified with pharmacy data. If inconsistent use is noted upon database search (this would NOT include changes in Suboxone dosing), then written explanation as to why Suboxone should be continued despite apparent noncompliance would be needed; Documentation of regular (every one to two months) urine tests that are negative for opiates since previous authorization; Documentation of consistent participation in formal counseling by a licensed behavioral health provider since previous authorization (D&A counselor is preferred, but not required). 12-step program participation, by itself, is not acceptable; Documentation of ongoing behavioral health care for co-existing behavioral health disorders. For patients consistently off opiates and taking Suboxone for an extended period of time and who have successfully completed prescribed formal D&A counseling programs, documentation of active engagement in after-care programs, such as NA or AA or equivalent, will be accepted instead of the above formal counseling requirement. If these criteria are met, then an additional 6 months of Suboxone will be authorized (1 month dispensed at a time). If the criteria are not met, psychiatrist review will be necessary to determine whether other factors would support medical necessity for continuation of Suboxone. FDA INDICATION: Buprenorphine HCl and buprenorphine HCl/naloxone are indicated for the treatment of opioid dependence. DOSAGE AND ADMINISTRATION: Buprenorphine HCl is administered sublingually or as a film, usually as a single daily dose, in the range of 12 to 16 mg/day. Buprenorphine HCl is preferred for use during induction. Following induction, buprenorphine HCl/naloxone, due to the presence of naloxone, is preferred when clinical use includes unsupervised administration. The use of buprenorphine HCl for unsupervised administration should be limited to those patients who cannot tolerate buprenorphine HCl/naloxone, for example those patients who have been shown to be hypersensitive to naloxone. Suboxone sublingual film should be used in patients who have been initially inducted using Subutex (buprenorphine) sublingual tablets. NOTE: It is assumed that since the prescribing practitioner has the appropriate DEA designation to prescribe this medication, the prescribing practitioner has had the full training in its proper use. REFERENCE: 1. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8 2. Suboxone/Subutex. Prescribing Information. Reckitt Benckiser Pharmaceuticals, Inc. August 2010. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Psychiatrist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

TRUE BLUE PRIOR AUTHORIZATION CRITERIA SYNAGIS (palivizumab): 50mg vial, 100mg vial PA CRITERIA FOR APPROVAL FOR FDA APPROVED INDICATIONS: The request for Synagis has all the following information submitted with the request: documentation of chronological age, gestational age, current weight, dose of medication and pertinent medical risk factors. If the child s current chronological age is less than 2 years of age at the beginning of Respiratory Syncytial Virus (RSV) season (July 1 st ), and the child has significant medical risk factors (chronic lung disease of prematurity (CLD) a.k.a. bronchopulmonary dysplasia (BPD)) requiring medical treatment either (i.e. supplemental oxygen, bronchodilator, diuretic or chronic corticosteroid therapy) within 6 months of the start of or during the current RSV season, severe immunodeficiencies/immunosuppression (see Table 3), or significant cardiac disease (i.e. those that require medication to control CHF, moderate to severe pulmonary hypertension or cyanotic heart disease) (see Table 1 & 2) that could be complicated by pulmonary disease. If the child was born prematurely with a gestational age of 28 weeks & 6 days or less, and the child s current chronological age is less than or equal to 1 year at the beginning of RSV season (July 1 st ). If the child was born prematurely with a gestational age between 29 and 31 weeks & 6 days and the child s current chronological age is less than or equal to 6 months at the beginning of RSV season (July 1 st ) Infants with congenital abnormalities of the airway or a neuromuscular disease that compromise handling of respiratory secretions during the first year of life. If the child has a gestational age of 32 till less than 35 weeks (i.e. 34 weeks & 6 days) and the child s current chronological age is less than 3 months at the beginning of RSV season (July 1 st ) or who were born during the RSV season and has increase risk of RSV exposure and the child has at least 1 of the following risk factors present: sibling(s) younger than 5 years old or other children that are younger than 5 years of age living in the same household or attends child care (defines as a home or facility where care is provided for any number of infants or young toddlers in the child care facility), OR exposure to one of the environmental air pollutants listed in Table 4.**IMPORTANT NOTE** These patients are only eligible to be approved a quantity of Synagis needed to treat the patient until he/she is 3 months (90 days) old OR until the end of March (a maximum of 3 doses), whichever is first. Hospitalized infants who qualify for Synagis prophylaxis during RSV season should received first dose 48 to 72 hours before discharge or directly after discharge. The request is for Synagis to be administered any time, but no more than once per 30 days, from July 1 st through the end of April, unless the prescribing physician provides epidemiology data that suggests RSV prophylaxis should start before July 1 st and/or continue beyond the end of April. If an infant or child who is receiving Synagis immunoprophylaxis experiences a breakthrough RSV infection, monthly prophylaxis should continue until a maximum of 3 doses have been administered to infants in the 32 weeks, 0 days' through 34 weeks, 6 days' gestation group, or until a maximum of 7 doses have been administered to infants with CHD, CLD, or preterm birth before 32 weeks' gestation. The prescribed dose of Synagis is in accordance with the FDA dosing recommendations. If the above conditions are met, the request will be approved with a quantity sufficient dependent on the patient s chronological age, gestational age, and/or clinical situation. For patients with a gestational age between 32 till less than 35 weeks (without any significant medical conditions) they will only be approved a maximum quantity of 3 doses. All other patients will be approved with a quantity sufficient to provide coverage from July 1 st through April April 30 th (a maximum quantity of 7 doses). If all of the above criteria are not met then, based on professional judgment, the Physician reviewer will issue a denial for the medication requested. FDA INDICATIONS: Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease. DOSAGE AND ADMINISTRATION: The recommended dose of Synagis is 15 mg/kg of body weight. Patients, including those who develop a RSV infection, should receive monthly doses throughout the RSV season. The first dose should be administered prior to commencement of the RSV season. **MAXIMUM APPROVABLE DOSES** 1. Patients born between 32 till less than 35 weeks of gestation, and without any significant medical conditions, will only receive Synagis treatment until they are 3 months (90 days) old (a maximum of 3 doses). Treatment with Synagis is not recommended for these patients past the age of 3 months old and, therefore, will not be approved. 2. For all other patients, they will only receive Synagis treatment for a maximum of 7 doses. There are no valid clinical reasons for an 8 th dose of Synagis and, therefore, all requests for an 8 th dose will be denied.

Table 1. Table 2. Table 3. Table 4. EXAMPLES OF SIGNIFICANT AND APPROVABLE CARDIAC CONDITIONS Examples of significant hemodynamic cyanotic congenital heart disease: Tetralogy of Fallot, Transportation of the great vessels, Ebstein s anomally, Tricuspid atresia, Total anomalous pulmonary venous return, Truncus arteriosus, Hypoplastic left heart syndrome Insignificant hemodynamic heart disease (and therefore are NOT approvable indications): Secundum atrial septal defect, small ventricular septal defect, pulmonic stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta, patent ductus arteriosus NON-APPROVABLE CARDIAC CONDITIONS Indications in which patients are NOT at an increased risk for RSV (and therefore are NOT approvable indications) Lesions adequately corrected by surgery (unless the patient continues to require medications for CHF) Mild cardiomyopathy who are NOT receiving medical therapy EXAMPLES OF SEVERE IMMUNODEFICIENCIES/IMMUNOSUPPRESSION: Advanced Acquired Immunodeficieny Syndrome (AIDS), Transplant, Chemotherapy, Severe Combined Immunodeficiency (SCID) APPROVABLE ENVIRONMENTAL POLLUTANTS Paper mill, coal burning power plants, wood burning stoves REFERENCES: 1. Respiratory Syncytial Virus, Pickering et al., Red Book Rep Comm Inf Dis, 1 (1), p. 609 2. American Academy of Pediatrics: Committee on Infectious Diseases and Committee on Fetus and Newborn, Prevention of respiratory syncytial virus infections: Indications for the use of Palivizumab and update on the use of RSV-IGIV. PEDIATRICS November 1998; Vol.102 No. 5:1211-1215. 3. American Academy of Pediatrics. [chapter title]. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2009: 562-568. 4. Facts and Comparisons, St. Louis, 2005 efacts CliniSphere Version ISBN 1-57439-036-8. 5. NREVSS: RSV Surveillance: Trends in the U.S. April 14, 2008. Available at : http://www.cdc.gov/surveillance/nrevss/index.htm. Accessed April 2008. 6. Update: Respiratory Syncytial Virus Activity United States, 1995-96 Season. December 8, 1995: 44(48); 900-902. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00039753.htm. Accessed April 2008. 7. RSV Surveillance 2005-2006: A Nationwide Hospital and Office-Based RSV Epidemiology Pilot Study. Pan American Society for clinical Virology. March 2007: 34; 1-9. 8. Synagis Package Insert, MedImmune, Inc/Ross, Gaithersburg, MD. April 2011. Revision/Review Date: 9/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary

Formulary Status: Non-Formulary TRUE HEALTH PRIOR AUTHORIZATION CRITERIA Tarceva (erlotinib): 25mg, 100 mg, and 150 mg tablets PRIOR AUTHORIZATION CRITERIA FOR INITIAL APPROVAL FOR NON-SMALL CELL LUNG CANCER: Documentation of a confirmed diagnosis of locally advanced or metastatic non-small cell lung cancer. AND Documentation that the patient has had an adequate trial and their cancer progressed on a previous chemotherapy regimen or has another medical reason (intolerance, hypersensitivity, etc) for not utilizing any other therapies to manage their medical condition.. AND Documentation that the patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of between 0-2 1. AND The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of up to 6 months; if all of the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PRIOR AUTHORIZATION CRITERIA FOR INITIAL APPROVAL FOR PANCREATIC CANCER: Documentation of a confirmed diagnosis of locally advanced, unresectable, or metastatic pancreatic cancer. AND Documentation that Tarceva is being used in combination with Gemzar (gemcitabine). AND The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of up to 6 months; if all of the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PRIOR AUTHORIZATION CRITERIA FOR INITIAL RE - APPROVAL FOR PANCREATIC or NON-SMALL CELL LUNG CANCER: The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. AND Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication. AND If the request is for a dosage increase of greater than 100 mg/day for patients with pancreatic cancer or 150 mg/day for patients with non-small cell lung cancer, documentation that Tarceva is being coadministered with a CYP3A4 inducer and rationale for why another medication could not be used to manage their medical condition If the above conditions are met, the request will be approved for a duration of 12 months; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED

INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. AND The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, Drug Points and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). AND Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). AND The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). If all of the above conditions are met, the request will be approved for a duration of up to 12 weeks. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. AND The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, Drug Points and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). AND Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication If all of the above conditions are met, the request will be approved for a duration of up to 12 weeks. If all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA APPROVED INDICATIONS: Non-Small Cell Lung Cancer: Tarceva monotherapy is indicated for the treatment of patients with locally advanced or metastatic Non- Small Cell Lung Cancer after failure of at least one prior chemotherapy regimen. Pancreatic Cancer: Tarceva in combination with gemcitabine is indicated for the first line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer. DOSAGE AND ADMINISTRATION: Non-Small Cell Lung Cancer: The recommended daily dose of Tarceva is 150 mg taken at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs. There is no evidence that treatment beyond progression is beneficial. Pancreatic Cancer: The recommended daily dose of Tarceva is 100 mg taken at least one hour before or two hours after the ingestion of food, in combination with Gemzar (gemcitabine). Treatment should continue until disease progression or unacceptable toxicity occurs.

DOSING MODIFICATION: When dose modifications are made due to an adverse reaction, the dose of Tarceva should be reduced in 50 mg increments. Dose modifications due to concomitant use of CYP3A4 inhibitors/inducers: Strong CYP3A4 inhibitors (i.e. azole antifungals, clarithromycin, nefazodone, protease inhibitors and telithromycin): An alternate medication for the CYP3A4 enzyme inhibitor should be investigated first, however if Tarceva must be administered with a potent enzyme inhibitor then dose reductions should be considered if a severe adverse reaction occurs. CYP3A4 inducers (i.e. dexamethasone, phenytoin, carbamazepine, phenobarbital, rifamycins or St. John s wart): An alternate medication for the CYP3A4 enzyme inducer should be investigated first, however if Tarceva must be administered with a potent enzyme inducer then an increase in dose may be required. Any dosage increase should occur at two week intervals while monitoring the patient s safety. The maximum dose of Tarceva studied in combination with rifampicin is 450 mg/day. When the strong CYP3A4 inducer is discontinued, the dose of Tarceva should be immediately reduced to the starting dose for the indication. 1 Eastern Cooperative Oncology Group (ECOG) Performance Status Grade ECOG 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed to chair more than 50% of waking hours 4 Completely disable. Cannot carry on any selfcare. Totally confined to bed to chair 5 Dead Reference: 1. Eastern Cooperative Oncology Group Performance Status. Available from http://ecog.dfci.harvard.edu/general/perf_stat.html. ccessed April 2008. 2. Tarceva Prescribing Information. Genentech, Inc. April 2009. 3. NCCN Clinical Practice Guidelines in Oncology : Non-Small Cell Lung Cancer, V.2.2009 Update. 4. NCCN Clinical Practice Guidelines in Oncology : Pancreatic Adenocarcinoma, V.1.2009 Update. 5. Shepherd FA, Pereira JR, Ciuleanu T, et al. Erlotinib in Previously Treated Non-Small-Cell Lung Cancer. N Eng J Medicine 2005; 353: 123-32. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. TRUE HEALTH PRIOR AUTHORIZATION CRITERIA

THIAZOLIDINEDIONES (TZDs) FORMULARY STATUS: Non-Formulary ACTOS (pioglitazone) Tablet: 15mg, 30mg, 45mg ACTOPLUS MET (metformin/pioglitazone) Tablet: 500mg/15mg, 850mg/15mg ACTOPLUS MET XR (metformin/pioglitazone) Tablet: 1000mg/15mg, 1000mg/30mg AVANDAMET (metformin/rosiglitazone) Tablet: 500/2mg, 500/4mg, 1000/2mg, 1000/4mg AVANDARYL (glimepiride/rosiglitazone) Tablet: 1/4mg, 2/4mg, 2/8mg, 4/4mg, 4/8mg AVANDIA (rosiglitazone) Tablet: 2mg, 4mg, 8mg DUETACT (glimepiride/pioglitazone) Tablet: 2mg/30mg, 4mg/30mg PA CRITERIA FOR APPROVAL: Diagnosis of Type 2 diabetes mellitus AND Documented trial and failure with therapeutic doses or intolerance to metformin (first-line therapy) AND Documented trial and failure with therapeutic doses or intolerance to Januvia, Janumet or Onglyza (second-line therapy). If member has a history of Januvia, Janumet or Onglyza or is currently taking an insulin product or currently taking Byetta, Symlin, or Victoza, this step is not required. If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: ACTOS (pioglitazone): Type 2 diabetes mellitus (noninsulin dependent, NIDDM), monotherapy: Adjunct to diet and exercise, to improve glycemic control. Type 2 diabetes mellitus (noninsulin dependent, NIDDM), combination therapy with sulfonylurea, metformin, or insulin: when diet, exercise, and a single agent alone does not result in adequate glycemic control. ACTOPLUS MET, ACTOPLUS MET XR (metformin/pioglitazone): Type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise. AVANDIA (rosiglitazone): Type 2 diabetes mellitus (noninsulin dependent, NIDDM), monotherapy: Adjunct to diet and exercise, to improve glycemic control. Type 2 diabetes mellitus (noninsulin dependent, NIDDM), combination therapy with sulfonylurea or metformin: when diet, exercise, and a single agent alone does not result in adequate glycemic control. AVANDAMET (metformin/rosiglitazone): Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise in patients where dual rosiglitazone and metformin therapy is appropriate AVANDARYL (glimepiride/rosiglitazone): Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise. DUETACT (glimepiride/pioglitazone): Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise. DOSAGE AND ADMINISTRATION: ACTOS (pioglitazone): Monotherapy: Initial: 15-30 mg once daily; if response is inadequate, the dosage may be increased in increments up to 45 mg once daily; maximum recommended dose: 45 mg once daily Combination therapy: Maximum recommended dose: 45 mg/day With sulfonylureas: Initial: 15-30 mg once daily; dose of sulfonylurea should be reduced if the patient reports hypoglycemia With metformin: Initial: 15-30 mg once daily; it is unlikely that the dose of metformin will need to be reduced due to hypoglycemia With insulin: Initial: 15-30 mg once daily; dose of insulin should be reduced by 10% to 25% if the patient reports hypoglycemia or if the plasma glucose falls to below 100 mg/dl Dosage adjustment in patients with CHF (NYHA Class II) in mono- or combination therapy: Oral: Initial: 15 mg once daily; may be increased after several months of treatment, with close attention to heart failure symptoms ACTOPLUS MET (metformin/pioglitazone): Initial dose should be based on current dose of pioglitazone and/or metformin; metformin dose may be titrated every 1-2 weeks and pioglitazone dose may be titrated every 2-3 months as necessary to achieve goals. Initial: Pioglitazone 15 mg plus metformin 500 mg or pioglitazone 15 mg plus metformin 850 mg tablets once or twice daily. Maximum daily dose: Pioglitazone 45 mg/metformin 2550 mg.

Daily doses higher than pioglitazone 15 mg plus metformin 850 mg should be divided. ACTOPLUS MET XR (metformin/pioglitazone): Pioglitazone 15 mg plus metformin 1000 mg tablet or pioglitazone 30 mg plus metformin 1000 mg tablet once daily with evening meal. Maximum daily dose: Pioglitazone 45 mg/metformin 2000 mg. AVANDIA (rosiglitazone): Monotherapy: Initial: 4 mg daily as a single daily dose or in divided doses twice daily. If response is inadequate after 8-12 weeks of treatment, the dosage may be increased to 8 mg daily as a single daily dose or in divided doses twice daily. In clinical trials, the 4 mg twice-daily regimen resulted in the greatest reduction in fasting plasma glucose and Hb A 1c Combination therapy: With sulfonylureas or metformin (or sulfonylurea plus metformin): Initial: 4 mg daily as a single daily dose or in divided doses twice daily. If response is inadequate after 8-12 weeks of treatment, the dosage may be increased to 8 mg daily as a single daily dose or in divided doses twice daily. Reduce dose of sulfonylurea if hypoglycemia occurs. It is unlikely that the dose of metformin will need to be reduced due to hypoglycemia. AVANDAMET (metformin/rosiglitazone): First-line therapy (drug-naive patients): Initial: Rosiglitazone 2 mg and metformin 500 mg once or twice daily; may increase by 2 mg/500 mg per day after 4 weeks to a maximum of 8 mg/2000 mg per day. Second-line therapy: Patients inadequately controlled on metformin alone: Initial dose: Rosiglitazone 4 mg/day plus current dose of metformin Patients inadequately controlled on rosiglitazone alone: Initial dose: Metformin 1000 mg/day plus current dose of rosiglitazone Dose adjustment: Doses may be increased as increments of rosiglitazone 4 mg and/or metformin 500 mg, up to the maximum dose; doses should be titrated gradually. After a change in the metformin dosage, titration can be done after 1-2 weeks. After a change in the rosiglitazone dosage, titration can be done after 8-12 weeks. Maximum dose: Rosiglitazone 8 mg/metformin 2000 mg daily. AVANDARYL (glimepiride/rosiglitazone): Initial: Rosiglitazone 4 mg and glimepiride 1 mg once daily or rosiglitazone 4 mg and glimepiride 2 mg once daily (for patients previously treated with sulfonylurea or thiazolidinedione monotherapy). Dose adjustment in patients previously on sulfonylurea monotherapy: May take 2 weeks to observe decreased blood glucose and 2-3 months to see full effects of rosiglitazone component. If not adequately controlled after 8-12 weeks, increase daily dose of rosiglitazone component. Dose adjustment in patients previously on thiazolidinedione monotherapy: If not adequately controlled after 1-2 weeks, increase daily dose of glimepiride component in 2 mg increments in 1-2 week intervals. Maximum dose: Rosiglitazone 8 mg and glimepiride 4 mg once daily DUETACT (glimepiride/pioglitazone): Patients inadequately controlled on glimepiride alone: Initial dose: 30 mg/2 mg or 30 mg/4 mg once daily. Patients inadequately controlled on pioglitazone alone: Initial dose: 30 mg/2 mg once daily. Patients with systolic dysfunction (eg, NYHA Class I and II): Initiate only after patient has been safely titrated to 30 mg of pioglitazone. Initial dose: 30 mg/2 mg or 30 mg/4 mg once daily. Maximum dose: Pioglitazone 45 mg/glimepiride 8 mg daily. BLACK BOX WARNING: ACTOS (pioglitazone), ACTOPLUS MET ACTOPLUS MET XR (metformin/pioglitazone), DUETACT (glimepiride/pioglitazone): Thiazolidinediones, including pioglitazone, may cause or exacerbate heart failure; closely monitor for signs and symptoms of heart failure (eg, rapid weight gain, dyspnea, edema), particularly after initiation or dose increases. Not recommended for use in any patient with symptomatic heart failure. In the U.S., initiation of therapy is contraindicated in patients with NYHA class III or IV heart failure; if used in patients with NYHA class II (systolic) heart failure, initiate at lowest dosage and monitor closely. In Canada, use is contraindicated in patients with any stage of heart failure (NYHA I, II, III, IV). Use with caution in patients with edema; may increase plasma volume and/or cause fluid retention. Dose reduction or discontinuation is recommended if heart failure suspected AVANDIA (rosiglitazone), AVANDAMET (metformin/rosiglitazone), DUETACT (glimepiride/pioglitazone): Thiazolidinediones, including rosiglitazone, may cause or exacerbate congestive heart failure; closely monitor for signs and symptoms of congestive heart failure (eg, rapid weight gain, dyspnea, edema), particularly after initiation or dose increases. Not recommended for use in any patient with symptomatic heart failure. In the U.S., initiation of therapy is contraindicated in patients with NYHA class III or IV heart failure; in Canada, use is contraindicated in patients with any stage of heart failure (NYHA I, II, III, IV). Use with caution in patients with edema; may increase plasma volume and/or cause fluid retention. A higher frequency of cardiovascular events has been noted in patients with NYHA class I or II heart failure treated with rosiglitazone. Use may also be associated with an increased risk of angina and MI. Use with caution in patients at risk for cardiovascular events and monitor closely. Discontinue if any deterioration in cardiac status occurs. Rosiglitazone (Avandia ): Modification of the Risk Evaluation and Mitigation Strategy (REMS) - May 2011 The U.S. Food and Drug Administration (FDA) has notified healthcare professionals and patients that access to rosiglitazone (Avandia ) and rosiglitazone-containing medicines (Avandamet, Avandaryl ) will be restricted as part of a modification to the current risk evaluation and mitigation strategy (REMS) program. The modified REMS program, known as the Avandia-Rosiglitazone Medicines Access Program, will include a medication guide and a restricted access and distribution program.

The Avandia-Rosiglitazone Medicines Access Program restricts access to rosiglitazone-containing medicines to the following group of patients: - Patients currently clinically benefitting from rosiglitazone. - Patients with type 2 diabetes who cannot achieve adequate disease management with other antidiabetic agents or who are not willing to use pioglitazone-containing medications after consulting with their healthcare provider. In order to prescribe and receive rosiglitazone-containing medicines, the prescriber and patient must be enrolled in the Avandia- Rosiglitazone Medicines Access Program. For enrollment, healthcare providers are required to review the rosiglitazone medicine prescribing information (including the medication guide), and complete an enrollment form. After November 18, 2011, GlaxoSmithKline will withdraw all rosiglitazone-containing products from the current supply chain and product will no longer be available in retail pharmacies. At that time, rosiglitazone-containing medicines will only be available through specially certified pharmacies participating in the program. REFERENCES: 1. Actos. Prescribing Information. Takeda Pharmaceuticals America, Inc. June 2011. 2. Actoplus Met. Prescribing Information. Takeda Pharmaceuticals America, Inc. June 2011. 3. Actoplus Met XR. Prescribing Information. Takeda Pharmaceuticals America, Inc. June 2011. 4. Avandamet. Prescribing Information. GlaxoSmithKline. May 2011. 5. Avandaryl. Prescribing Information. GlaxoSmithKline. May 2011. 6. Avandia. Prescribing Information. GlaxoSmithKline. May 2011. 7. Duetact. Prescribing Information. Takeda Pharmaceuticals America, Inc. June 2011. 8. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 9. American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control. Endocrine Practice 2009;15(6):540-59. 10. American Diabetes Association. Standards of medical care in diabetes 2010. Diabetes Care. January 2010;33(suppl 1):S11-S61. 11. Lexicomp online. Updated August 2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

Field Name Prior_Authorization_Group_Desc Drug(s) Covered_Uses Exclusion_Criteria Required_Medical_Information Age_Restrictions Prescriber_Restrictions Coverage_Duration Other_Criteria Field Description METOPROLOL SUCCINATE Toprol XL (metoprolol succinate) *Medically accepted indications are defined using the following sources: the Food and Drug Administration (FDA), Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), and the Drug Package Insert). None Diagnosis of CHF, hypertension, or other cardiac conditions. None None If the above conditions are met, the request will be approved indefinitely. Members will be grandfathered indefinitely. For CHF or other Cardiac Conditions: Diagnosis of congestive heart failure (CHF) or other cardiac conditions (including Angina, A. Fib, CAD, etc.) For Hypertension: Diagnosis of hypertension AND documented trial and failure or intolerance with therapeutic doses and length of therapies with at least three other classes of antihypertensive medications. NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. Revision/Review Date: 5/2014 Associated Policy: Prior Authorization of Prescription Drugs 236.200

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA TRANSDERM-SCOP (scopolamine) Patch: 1.5mg FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Motion Sickness: Diagnosis of nausea and vomiting associated with motion sickness or recovery from anesthesia AND Documented trial and failure at therapeutic doses, intolerance or contraindication to meclizine, diphenhydramine If the above conditions are met, the request will be approved with a one month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. Sialorrhea: Documented trial and failure at therapeutic doses, intolerance or contraindication to glycopyrrolate If the above conditions are met, the request will be approved with a twelve month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Prevention of nausea and vomiting associated with motion sickness in adults and recovery from anesthesia and surgery. DOSAGE AND ADMINISTRATION: Apply one system to the post auricular skin (i.e., behind the ear) at least 4 hours before the antiemetic effect is required. Approximately 1mg of scopolamine will be delivered over 3 days. Wear only one disc at a time. Motion sickness: Apply 1 patch behind the ear at least 4 hours prior to exposure and every 3 days as needed; effective if applied as soon as 2-3 hours before anticipated need, best if 12 hours before. If therapy is required for longer than 3 days, the first patch should be removed and a fresh one placed on the post auricular skin behind the other ear. Preoperative: Transdermal patch: Apply 1 patch to hairless area behind ear the night before surgery or 1 hour prior to cesarean section (apply no sooner than 1 hour before surgery to minimize newborn exposure); remove 24 hours after surgery. REFERENCES: 1. Kranke P, et al. The efficacy and safety of transdermal scopolamine for the prevention of postoperative nausea and vomiting: a quantitative systemative review: Anesth Analg 2002 Jul; 95 (1): 133-43 2. Sandin D. Transderm scopolamine: A painless, noninvasive option for control of postoperative nausea and vomiting. J Perianesth Nurs 2002 Dec; 17 (6): 427-9 3. Transderm Scop (scopolamine patch) package insert. Novartis Consumer Health, Inc. February 2008. 4. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 5. Hockstien NG, et al. Sialorrhea: A management Challenge. American Family Physician. 2004;69(11):2628-34. 6. Mier RJ, Bachrach SJ, Lakin RC, et al. Treatment of sialorrhea with glycopyrrolate. A double blind dose ranging Study. Arch Pediatr Adolesc Med. 2000;154:1214-1218. 7. Arbouw ME, Movig KL, Koopmann M, et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010;74(15):1203-7. 8. Drug information online. Updated 02/2008. 9. Lexicomp online. Updated 08/2011 Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

Field Name Field Description Prior Authorization Group Descr: Drug(s) ANDROGENIC AGENTS ANDRODERM (testosterone) ANDROGEL (testosterone) TESTIM (testosterone) AXIRON (testosterone) ANDROID (testosterone) ANDROXY (testosterone) AXIRON (testosterone) DEPO-TESTOSTERONE (Testosterone Cypionate) FORTESTA (testosterone) METHITEST STRIANT BUCCAL TESTOPEL IMPLANT (testosterone) Testred (testosterone) TESTOSTERONE ENANTHATE (Delatestryl IM oil) Covered Uses Exclusion Criteria Required Medical Information Age Restrictions Prescriber Restrictions *Medically accepted indications are defined using the following sources: the Food and Drug Administration (FDA), Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), and the Drug Package Insert). None Prescriber must document medical reason for low testosterone, such as Hypogonadism. Copy of Laboratory Result Required, demonstrating testosterone level < 300ng/dl Member is an adult greater than or equal to 18 years of age. None Coverage Duration Other Criteria If all of the conditions are met, the request will be approved with 3 month duration. For re-authorization the request will be approved with 12-month duration. For Initial Authorization: Male patient Diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired) Documented testosterone level (s) below 300ng/dl (copy of laboratory result required) For Re-Authorization: Documentation indicating the member has clinically benefited from therapy. Repeat documented testosterone level (s) below 300ng/dl. NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary. Revision/Review Date: 5/2014 Associated Policy: Prior Authorization of Prescription Drugs 236.200

FLORIDA TRUE HEALTH PRIOR AUTHORIZATION CRITERIA TYKERB (lapatinib): Tablets: 250 mg STATUS: Non-Preferred PA CRITERIA FOR APPROVAL FOR BREAST CANCER: Diagnosis of advance and/or metastatic breast cancer. AND Documentation that the patient is human epidermal receptor type 2 (HER2) positive. AND Documentation that the patient is estrogen receptor and progesterone receptor negative or refractory to hormonal treatment or has symptomatic visceral disease. AND Documentation (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) that the patient has had an adequate trial (including dates and doses) at therapeutic doses with an anthracycline (i.e. Doxorubicin or Epirubicin) a taxane (i.e. Docetaxel or Paclitaxel) and Herceptin (trastuzumab). AND Documentation of concurrent use of Xeloda (capecitabine) or Femara (letrozole) AND The medication is being prescribed at a dose that is within FDA approved guidelines and/or is supported by the medical compendium as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO) standard of care guidelines. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR BREAST CANCER: The medication is being prescribed at an FDA approved dosage. AND Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication. AND If the request is for a dosage increase of greater than 1,250mg/day, documentation that Tykerb is being coadministered with a CYP3A4 inducer and rationale for why another medication could not be used to manage their medical condition. If the above conditions are met, the request will be approved for a duration of 6 months; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. PA CRITERIA FOR AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is prescribed for a non-fda approved indication but is considered to be a medically accepted use of the medication per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the 113 Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard care guidelines and/or has another documented medical reason (i.e. intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). The medication is prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer

Network (NCCN) or the American Society of Clinical Oncology (ASCO). If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Pharmacist for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN A NON-FDA APPROVED MEDICALLY ACCEPTED INDICATION: The medication is recommended and prescribed by a specialist in the field to treat the member s respective medical condition. The medication is being prescribed at a medically accepted dose per the medical compendia (i.e. Micromedex, DrugPoints [formerly known as USPDI] and AHFS drug information) as defined by the Social Security Act and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO). Documentation from medical charts indicating continuation of therapy due to the member significantly clinically benefited from the medication. If the request is for a dosage increase of greater than 1,250mg/day then documentation that Tykerb is being coadministered with a CYP3A4 inducer and rationale for why another medication could not be used to manage their medical condition. If all of the above conditions are met, the request will be approved for up to a 6 month duration. If all of the above criteria are not met, the request is referred to a Pharmacist for medical necessity review. FDA INDICATION: Breast Cancer In combination with capecitabine, this is approved for the treatment of patients with advanced breast cancer whose tumors overexpress human epidermal receptor type 2 (HER2) and who have received prior treatment with an athracycline, a taxane, and traztuzumab. Patients should have disease progression on trastuzumab prior to initiation of treatment with Tykerb in combination with capecitabine. In combination with letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. DOSAGE AND ADMINISTRATION: The recommended dosage of Tykerb is 1250mg (5 tablets) given once daily on days 1 to 21 continuously in combination with Xeloda 2,000mg/m2/day(given orally in two divided doses approximately 12 hours apart) on days 1 to 14 in a repeating 21 day cycle. The recommended dose of TYKERB for hormone receptor-positive, HER2-positive metastatic breast cancer is 1,500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When TYKERB is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily. Tykerb should be taken at least 1 hour before or after meals. However, capecitabine should be taken with food or within 30 minutes after food. The dosage of Tykerb should be given once daily; dividing the dosage in not recommend. Treatment should continue until disease progression or unacceptable toxicity occurs. DOSAGE ADJUSTMENT Hepatic impairment: Severe hepatic impairment (Child-Pugh class C) (1) In combination with capecitabine: Reduce dose from 1250 mg once daily to 750 mg once daily. (2) In combination with letrozole: Reduce dose from 1500 mg once daily to 1000 mg once daily. Cardiac events: Tykerb should be discontinued in patients with a decreased left ventricular ejection fraction (LVEF) that is a Grade 2 or greater by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) and in patients with a LVEF that drops below the institution s lower limit of normal. Tykerb in combination with capecitabine may be restarted at a reduced dose (1,000 mg/day) and in combination with letrozole may be restarted at a reduced dose of 1,250 mg/day after a minimum of 2 weeks if the LVEF recovers to normal and the patient is asymptomatic.

In renal impairment: Due to the minimal renal elimination (<2%), dosage adjustments for renal dysfunction may not be necessary. Diarrhea: Tykerb should be interrupted in patients with diarrhea which is NCI CTCAE Grade 3 or Grade 1 or 2 with complicating features (moderate to severe abdominal cramping, nausea or vomiting NCI CTCAE Grade 2, decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration). TYKERB may be reintroduced at a lower dose (reduced from 1,250 mg/day to 1,000 mg/day or from 1,500 mg/day to 1,250 mg/day) when diarrhea resolves to Grade 1 or less. TYKERB should be permanently discontinued in patients with diarrhea which is NCI CTCAE Grade 4 Pulmonary toxicity: Discontinue treatment with pulmonary symptoms indicative of interstitial lung disease or pneumonitis which are grade 3 Due to concomitant use of CYP3A4 inhibitors/inducers: Strong CYP3A4 inhibitors (i.e. azole antifungals, clarithromycin, nefazodone, protease inhibitors and telithromycin): An alternate medication for the CYP3A4 enzyme inhibitor should be investigated first, however if Tykerb must be administered with a potent enzyme inhibitor then dose reductions are likely to be necessary. Consider reducing Tykerb to 500 mg once daily with careful monitoring. When a strong CYP3A4 inhibitor is discontinued, the provider should allow one week to elapse before titrating the dose upward. CYP3A4 inducers (i.e. dexamethasone, phenytoin, carbamazepine, phenobarbital, rifamycins, and St. John s wart): An alternate medication for the CYP3A4 enzyme inducer should be investigated first, however if Tykerb must be administered with a potent enzyme inducer then an increase in dose may be required. The dose may be increased gradually to 4500mg/day (in combination with capecitabine) or to 5500 mg daily (in combination with letrozole) with careful monitoring. When a strong CYP3A4 inducer is discontinued, the dose of Tykerb should be reduced to the indicated dose REFERENCES: 1. NCCN Clinical Practice Guidelines in Oncology : Breast Cancer; V.2.2007. 2. Tykerb Prescribing Information, GlaxoSmithKline Pharmaceutical, 2013. 3. Lexicomp 2014. 4. Geyer CE, Forster J, Lindquist D, et. al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. N Engl J Med 2006; 355:2733-43. Revision/Review Date: 01/2014 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Pharmacist review must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA TYSABRI (natalizumab): 300mg/15mL single use vial Formulary Status: Non-Formulary requiring prior authorization PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN MULTIPLE SCLEROSIS (MS): The member is an adult ( 18 y/o) and has a clinical diagnosis of a relapsing form of multiple sclerosis. Clinical or diagnostic information was submitted that indicates that that patient has a documented (consistent with pharmacy claims data OR for new members to the health plan consistent with medical chart history) treatment failure (see Box 1 for definition of treatment failure) after receiving an adequate trial (including dates, doses of 6 months or more of each therapy) of interferon Beta- 1A (Rebif ) and glatiramer acetate (Copaxone ) or has a some other documented medical reason (intolerance, hypersensitivity, etc) for not utilizing all of these therapies for a minimum of 6 months each to manage their medical condition. Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. TYSABRI is being prescribed by a neurologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR REAUTHORIZATION FOR USE IN MS: The member is an adult ( 18 y/o) and has a current clinical diagnosis of a relapsing form of multiple sclerosis. Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence) that indicates the member has significantly clinically benefited from receiving TYSABRI therapy. Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. TYSABRI is being prescribed by a neurologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL APPROVAL FOR CROHN S DISEASE: The member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn s Disease The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) at therapeutic doses or has some documented clinically significant medical reason for not receiving oral conventional therapy to manage their medical condition. The patient has a documented (consistent with pharmacy claims data, OR for new members to the health plan consistent with medical chart history) adequate trial (including dates and doses) with therapeutic doses of or has some documented clinically significant medical reason for not receiving Humira (adalimumab). TYSABRI is being prescribed by a gastroenterologist at an FDA approved dosage. PA CRITERIA FOR REAUTHORIZATION FOR USE IN CROHN S DISEASE: Documentation was submitted indicating that the member is an adult ( 18 y/o) and has a documented clinical diagnosis of moderate to severely active Crohn s Disease Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence) that indicates the member has significantly clinically benefited from receiving TYSABRI therapy. Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. TYSABRI is being prescribed by a gastroenterologist at an FDA approved dosage. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR INITIAL AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: The medication is recommended and prescribed a specialist in the field to treat the member s respective medical condition.

The medication is prescribed for a medically accepted use per the medical compendia (i.e. Micromedex, Drug Points, AHFS drug information) as defined by the Social Security Act. Documentation was submitted indicating that the member has a documented (consistent with pharmacy claims data) adequate trial (including dates, doses of medications) of all first line medical therapies as recommended by the medical compendia and standard of care guidelines or has a documented medical reason ( intolerance, contraindications, etc.) for not receiving or trying all first line medical treatment(s). Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. Documentation on request form indicates that the medication is recommended or prescribed by a physician who is authorized by the TOUCH program to prescribe TYSABRI and that the patient is enrolled in the TOUCH program and has agreed to comply with the requirements for receiving TYSABRI. The medication is prescribed at a medically accepted dose per the medical compendia as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR RE-AUTHORIZATION FOR USE IN OTHER MEDICALLY ACCEPTED INDICATIONS: The medication is recommended or prescribed by a specialist for the respective treated disease state. Diagnostic or clinical documentation was submitted (e.g. improved disease activity index, quality of life, blood work, radiographic evidence) that indicates the member has significantly clinically benefited from receiving TYSABRI therapy. Documentation on request form indicates that the medication is recommended or prescribed by a physician who is authorized by the TOUCH program to prescribe TYSABRI and that the patient is enrolled in the TOUCH program and has agreed to comply with the requirements for receiving TYSABRI. Documentation consistent with pharmacy claims data was submitted indicating the patient is not currently using any antineoplastic, immunosuppressant, or immunomodulating medications and does not have a history of progressive multifocal leukoencephalopathy (PML) and does not have a compromised immune system. Documentation that, and is being prescribed at a medically accepted dose per the medical compendia (i.e. micromedex, Drug Points, AHFS) as defined by the Social Security Act. If all of the above conditions are met, the request will be approved for up to a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATIONS: Multiple Sclerosis: Tysabri is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis in order to delay the accumulation of physical disability and to reduce frequency of clinical exacerbations. Tysabri is generally recommended for patients who have an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies. Crohn s Disease: Tysabri is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn s disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate conventional Crohn s disease therapies and inhibitors to TNF-α. DOSAGE AND ADMINISTRATION: 300 mg IV infused over approximately 1 hour, given at 4-week (28-day) intervals. Do not give as an intravenous push or bolus. BOX 1: TREATMENT FAILURE: A member may be considered to have failed treatment if any of the following are documented: 1. Member who has an attack rate (relapse) of more than 1 per year, fails to show a reduction in relapse rate, or continues to experience attacks (relapses) at a rate similar to that found before starting therapy** 2. Member who has incomplete recovery (cumulative residual abnormalities sustained for 6 months) from repeated attacks, particularly as the EDSS score increases. ** 3. Member experiences an annual increase in the EDSS (Expanded Disability Status Scale) of 1 point from a previous score of 3 to 5.5, or 0.5 point increase from a previous score of 6.0 or greater in the absence of clinical attacks or other documentation of clinically significant disability progression. ** 4. Member who develops new or recurrent brainstem or spinal cord lesions as seen on MRI. ** 5. Members experiencing relapses affecting multiple neurologic symptoms, and those accumulating residual impairments in multiple neurologic systems. **

6. Members who have progressive motor, cognitive or sensory impairment sufficient to disrupt their daily activities irrespective of changes on neurologic examination, provided the influence of depression, medications or superimposed concurrent disease is ruled out. Examples include: loss of endurance in sustaining activity, forced alterations in activities of daily living, muddled thinking, impaired concentration and mental processing and fatigue. ** 7. Members who have new or enlarging T2 lesions, brain atrophy on MRI, or new T1 Gd enhancing lesions on MRI accompanied by changes in the ability to perform daily activities. ** ** These are members who have a documented treatment failure after receiving a minimum of 6 months each of Copaxone and Rebif. Diagnostic or clinical documentation of treatment failure will be required for the last therapy the member received. This requires that he member has failed a minimum of 6 months of all 3 available therapies (Rebif and Copaxone) or has a documented medical reason (i.e. intolerance) for not utilizing all 3 therapies for a minimum of 6 months. GLOSSARY: TOUCH : is a distribution program designed to assess the risk of progressive multifocal leukoencephalopathy (PML) associated with TYSABRI, minimize the risk of PML, minimize the death and disability due to PML, and promote informed risk-benefit decisions regarding TYSABRI use. Kurtzke Expanded Disability Scale (EDSS) score: is a scale for evaluating the degree of neurologic impairment in MS. The EDSS score is measured in one-half point increments, from 0.0 (normal) to 10.0 (death). In order to rate a person on the EDSS, the neurologist first performs a standard neurologic examination to test strength, coordination, vision, walking, etc. The neurologist next summarizes the results of the neurological examination in several Functional System Scores as follows: pyramidal (strength and spasticity), cerebellar, brain stem, sensory, bowel and bladder, visual, cerebral and other functions. Finally, the neurologist uses the Functional System Scores along with ability to walk to rate the individual on the EDSS. The EDSS score is most reflective of lower limb function. Since this scoring system does not account for other signs and symptoms of MS, it is not used as an absolute measure of disability. But the EDSS can be a good gauge of disease progression. Other scales are used to measure fatigue, symptoms affecting the upper body, and mental changes. Kurtzke Expanded Disability Status Scale (EDSS) Rating Status 0 Normal Neurological Exam 1.0 No Disability, minimal symptoms 1.5 No disability, minimal signs in more than one area 2.0 Slightly more disability in one area 2.5 Slightly greater disability in two areas 3.0 Moderate disability in one area but still walking independently 3.5 Walking independently but with moderate disability in one area and more than minimal disability in several others 4.0 Walking without aid, self-sufficient, up and about some12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters 4.5 Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters. 5.0 Walking without aid or rest for about 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions 5.5 Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities 6.0 Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting 6.5 Needs canes, crutches, braces to walk for 20 meters without resting 7.0 Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day 7.5 Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair 8.0 Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms 8.5 Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions 9.0 Helpless bed patient; can communicate and eat 9.5 Totally helpless bed patient; unable to communicate effectively or eat/swallow 10.0 Death due to MS

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983;33:1444-1452. REFERENCES: 1. Cohen BA. Khan O. Jeffery DR. et al. Identifying and treating patients with suboptimal responses. Neurology.2004;63(Suppl 6):S33-S40. 2. Lee MA. Smith L. Palace J. et al. Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis.? Brain.199;122:1261-1270. 3. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006; 245:111-116. 4. Brex P. Ciccarelli O. O Riordan J. et al. A longitudinal study of abnormalities on MRI and disability from MS. The New England Journal of Medicine.2002; 246(3):158-164. 5. Miller DH. Grossman RI. Reingold SC. Et al The role of magnetic resonance techniques in understanding and managing MS. Brain.1998; 121:3-24. 6. Lycklama GJ. Van Walderveen MAA. Castelijns JA. Et al. Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain.1998; 121:687-697. 7. O Riordan JI. Thompson AJ. Kingsley DPE. et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain.1998;121:495-503. 8. Rooney WD. Coyle PK. Recent advances in the neuroimaging of MS.Current Neurology and Neuroscience Reports.2005;5:217-224. 9. Polman CH, O'Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910. 10. Dalton CM. Miszkiel KA. Barker DG. Et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. Journal of Neurology.2004; 251:407-413. 11. Tysabri package insert. Cambridge, MA: Biogen Idec; March 2011. 12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology.1983; 33:1444-1452. 13. Rovaris M. Comi G. Filippi M. MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction. Journal of the Neurological Sciences.2006; 245:111-116. 14. Polman CH. Reingold SC. Edan G. et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the McDonald Criteria. Annals of Neurology.2005; 58:840-846. 15. Rudick, RA. Lee JC. Simon J. Fisher E. Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study. Annals of Neurology.2006;60:236-242. 16. Rieckmann P. Toyka KV. Escalating immunotherapy of multiple sclerosis. New aspects and practical application. Multiple Sclerosis Therapy Consensus Group (MSTCG). Journal of Neurology. 2004;251:1329-1339. 17. Leary SM. Porter B. Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medicine Journal. 2005;81:302-308. 18. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Disease management consensus statement.2005. Available at www.nationalmssociety.org/prc.asp 19. National Multiple Sclerosis Society. Expert Opinion Paper. Medical advisory board of the National MS Society. Treatment recommendations for physicians. Changing therapy in relaspsing multiple sclerosis: Considerations and recommendations of a task force of the National MS Society.2004. Available at www.nationalmssociety.org/prc.asp 20. Rio J. Nos C. Tintore M. et al. Assessment of different treatment failure criteria in a cohort of RRMS patients treated with interferon β: implications for clinical trials. Annals of Neurology. 2002;52:400-406. 21. Rio J. Nos C. Tintore M. et al. Defining the response to interferon-β in RRMS patients. Annals of Neurology.2006; 59:344-352. 22. Goodin DS. Arnason BG. Coyle PK. Et al. The use of mitoxantrone (Novantrone) for the treatment of MS. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology.2003; 61:1332-1338. 23. Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab Induction and Maintenance Therapy for Crohn s Disease. The New England Journal of Medicine 2005; 353: 1912-25. 24. Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the Treatment of Active Crohn s Disease: Results of the ENCORE Trial. Gastroenterology 2007; 132: 1672-83. 25. Feagan BG, Sandborn WJ, Hass S, et al. Health-Related Quality of Life During Natalizumab Maintenance Therapy for Crohn s Disease. American Journal of Gastroenterology 2007; 102:2737-46. Revision/Review Date: 6/2011 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ULORIC (febuxostat) Tablet: 40 mg, 80 mg STATUS: Non-preferred PA CRITERIA FOR APPROVAL: 1. Trial and failure of maximized doses of allopurinol. Up to 800mg of allopurinol per day should have been attempted prior to treatment with febuxostat (depending on renal status). If the above conditions are met, the request will be approved with a 12 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS: For the chronic management of hyperuricemia in patients with gout. Febuxostat is not recommended for the treatment of asymptomatic hyperuricemia. DOSAGE AND ADMINISTRATION: Management of hyperuricemia in patients with gout: Note: It is recommended to take an NSAID or colchicine with initiation of therapy and may continue for up to 6 months to help prevent gout flares. If a gout flare occurs, febuxostat does not need to be discontinued. Initial: 40 mg once daily; may increase to 80 mg once daily in patients who do not achieve a serum uric acid level <6 mg/dl after 2 weeks. REFERENCES: 1. Uloric [package insert]. Deerfield, IL: Takeda Pharmaceuticals America; January 2011. 2. Bruce SP, Febuxostat: A Selective Xanthine Oxidase Inhibitor for the Treatment of Hyperuricemia and Gout, Ann Pharmacother, 2006, 40(12):2187-94. Revision/Review Date: 2/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA VANCOCIN (vancomycin) Capsule: 125mg, 250mg FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL: Staphylococcal Enterocolitis: Diagnosis of staphylococcal enterocolitis Pseudomembranous Colitis: Diagnosis of antibiotic associated pseudomembranous colitis produced by C. difficile. AND Documented trial and failure with therapeutic doses or intolerance to metronidazole. If the above conditions are met, the request will be approved with a 10 day duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis produced by C. difficile. Oral vancomycin is not effective for other types of infection. DOSAGE AND ADMINISTRATION Adults: 500 mg to 2 g/day given in 3 or 4 divided doses for 7 to 10 days. Alternatively, dosages of 125 mg 3 or 4 times daily for C. difficile colitis may be as effective as the 500 mg dose regimen. Children: 40 mg/kg/day in 3 or 4 divided doses for 7 to 10 days. Do not exceed 2 g/day. REFERENCE: 1. Silvestri L; Milanese M; Oblach L; Fontana F; Gregori D; Guerra R; van Saene HK. Enteral vancomycin to control methicillinresistant Staphylococcus aureus outbreak in mechanically ventilated patients. Am J Infect Control 2002 Nov;30(7):391-9. 2. Hussain FM; Boyle-Vavra S; Shete PB; Daum RS Evidence for a continuum of decreased vancomycin susceptibility in unselected Staphylococcus aureus clinical isolates. J Infect Dis 2002 Sep 1;186(5):661-. 3. Stevens DL; Herr D; Lampiris H; Hunt JL; Batts DH; Hafkin B. Linezolid versus vancomycin for the treatment of methicillinresistant Staphylococcus aureus infections. Clin Infect Dis 2002 Jun 1;34(11):1481-90. 4. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 5. Sanford Guide to Antimicrobial Therapy 2007. 6. Vancocin. Prescribing Information. ViroPharma. October 2005. 7. Sunenshine RH, McDonald LC. Clostridium difficile-associated disease: new challenges from an established pathogen. Cleveland Clinic Journal of Medicine 2006;73(2):187-97. Review Date: 7/2012 Associated Policy: Prior Authorization of Prescription Drugs 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA VFEND (voriconazole) Tablet: 50mg, 200mg, Oral Suspension 40 mg/ml FORMULARY STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of invasive aspergillosis or a serious fungal infection caused by Scedosporium apiospermum and Fusarium species If the above conditions are met, the request will be approved with up to a 3 month duration depending upon the severity of the infection; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Invasive aspergillosis Serious fungal infections: Treatment of serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in patients intolerant of, or refractory to other therapy. Candidemia in nonneutropenic patients and the following Candida infections: disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds Esopaghageal candidiasis DOSAGE AND ADMINISTRATION Invasive Aspergillosis*: 200 mg every 12 hours Candidermia in nonneutropenic patients and other deep tissue Candida Infections*: 200 mg every 12 hours Esophageal Candidiasis*: 200 mg every 12 hours Scedosporiosis and Fusariosis*: 200 mg every 12 hours Should be taken at least one hour before or one hour following a meal. *Dose based on patients who weigh > 40 kg. Dose Adjustment Give adult patients who weigh < 40 kg an oral maintenance dose of 100 mg every 12 hours. This dose can be increase to 150 mg every 12 hours. If patient response is inadequate, the oral maintenance dose may be increased from 200 mg every 12 hours to 300 mg every 12 hours. If patients are unable to tolerate 300 mg orally every 12 hours reduce the oral maintenance dose by 50 mg steps to a minimum of 200 mg every 12 hours (or to 100 mg every 12 hours for adult patients weighing less than 40 kg) Hepatic Insufficiency It is recommended that the standard loading dose regimens be used but the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child- Pugh Class A and B). REFERENCES: 1. Verweij PE, Te Dorsthorst DT, Rijs AJ, et al.nationwide survey of in vitro activities of itraconazole and voriconazole against clinical Aspergillus fumigatus isolates cultured between 1945 and 1998.J Clin Microbiol (United States), Jul 2002, 40(7) p2648-50. 2. Manavathu EK, Abraham OC, Chandrasekar PH.Isolation and in vitro susceptibility to amphotericin B, itraconazole and posaconazole of voriconazole-resistant laboratory isolates of Aspergillus fumigatus.clin Microbiol Infect (France), Mar 2001, 7(3) p130-7. 3. Shah KB, Wu TG, Wilhelmus KR, et al.activity of voriconazole against corneal isolates of Scedosporium apiospermum. Cornea (United States), Jan 2003, 22(1) p33-6 4. Herbrecht R, Denning DW, Patterson TF, et al.voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.n Engl J Med (United States), Aug 8 2002, 347(6) p408-15. 5. Denning DW, Ribaud P, Milpied N, et al.efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis.clin Infect Dis (United States), Mar 1 2002, 34(5) p563-71. 6. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 7. Vfend Prescribing Information. Pfizer Inc. March 2010. 8. Segal BH and Walsh TJ. Current Approaches to Diagnosis and Treatment of Invasive Aspergillosis. Am J Respir Crit Care Med. 2006;173:707-17. 9. Harman EM. Aspergillosis. emedicine. Available at: http://emedicine.medscape.com/article/296052-overview. Updated December 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA VICOPROFEN (hydrocodone/ibuprofen) Tablet: 7.5/200mg FORMULARY STATUS: Non-Formulary (generic) PA CRITERIA FOR APPROVAL: Diagnosis of acute pain. AND Documented trial and failure or intolerance to at least three of the following medications: oxycodone/acetaminophen, hydrocodone/acetaminophen, acetaminophen/codeine, morphine, and hydromorphone. If the above conditions are met, the request will be approved up to 3 month duration; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Vicoprofen tablets are indicated for the short term (generally less than 10 days) management of acute pain. Vicoprofen is not indicated for the treatment of such conditions as osteoarthritis or rheumatoid arthritis. DOSAGE AND ADMINISTRATION: For the short term (generally less than 10 days) management of acute pain, the recommended dose is one tablet every 4-6 hours, as necessary. Dosage should not exceed 5 tablets in a 24 hour period. REFERENCE: 1. Palangio M, Morris E, Doyle RT, et al.combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Clin Ther (United States), Jan 2002, 24(1) p87-99. 2. Barkin RL.Acetaminophen, aspirin, or Ibuprofen in combination analgesic products.am J Ther (United States), Nov-Dec 2001, 8(6) p433-42. 3. Facts and Comparisons, St. Louis, 2010 efacts CliniSphere Version ISBN 1-57439-036-8. 4. Vicoprofen Prescribing Information. Abbott Laboratories. October 2009. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA VIGAMOX (moxifloxacin ophthalmic solution): 0.5%(3mL) FORMULARY STATUS: Formulary PA CRITERIA FOR APPROVAL WRITTEN/REQUESTED BY OPHTHALMOLOGIST: Diagnosis and prescription by an ophthalmologist If the above condition is met, the request will automatically be approved with a 7-day course of therapy (one 3mL bottle). If the above condition is not met, the request will be referred to a Medical Director for medical necessity review. PA CRITERIA FOR APPROVAL NOT WRITTEN/REQUESTED BY OPHTHALMOLOGIST: Diagnosis of ocular bacterial conjunctivitis caused by susceptible strains of organisms and Diagnosis and prescription by primary care physician or healthcare provider not an ophthalmologist specialist and Documented trial and failure or intolerance to a full 7-day course of therapy to the formulary third generation ophthalmic fluoroquinolone (ofloxacin ophthalmic solution) If the above conditions are met, the request will be approved with a 7-day course of therapy (one 3mL bottle). If the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Vigamox (moxifloxacin ophthalmic solution): Treatment of bacterial conjunctivitis caused by susceptible strains of organisms: Aerobic Gram Positive Bacteria: Cornyebacterium species, Micrococcus luteus, Staphylococcus aureus, S. epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri, S. pneumoniae, Streptococcus viridans group Aerobic Gram Negative Bacteria: Acinetobacter/woffi, Haemophilus influenzae, Haemophilus parainfluenzae Other Microorganisms: Chlamydia trachomatis DOSAGE AND ADMINISTRATION: Vigamox (moxifloxacin ophthalmic solution): Instill 1 drop in the affected eye(s) three times a day for 7 days. Vigamox is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. REFERENCES: 1. Vigamox Product Information. Alcon, Inc. 2006. 2. Fish DN, et al. Gatifloxacin, An Advanced 8-Methoxy Flouroquinolone. Pharmacotherapy. 2001; (1):35-59. 3. Drugs Facts and Comparisons. 2010. Vigamox & Zymar available from http://online.factsandcomparisons.com. Accessed December 2010. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

PRIOR AUTHORIZATION CRITERIA FOR WHITE BLOOD CELL STIMULATORS Neupogen (filgrastim) 300 mcg/ml preservative-free (PF) vial, 300 mcg/0.5 ml prefilled syringe PF; 480 mcg/1.6 ml PF vial, 480 mcg/0.8 ml prefilled syringe PF. Leukine (sargramostim) 250 mcg lyophilized powder for injection PF vial, 500 mcg/ml solution multi-dose vial * Neulasta (pegfilgrastim) 6 mg/0.6ml prefilled syringe for subcutaneous injection PA CRITERIA FOR INITIAL APPROVAL The request for the medication is for an Food and Drug Administration (FDA) approved indication, and/or is used for a medical condition (see medically accepted uses section below) that is supported by the medical compendium (Micromedex, American Hospital Formulary Service (AHFS), Drug Points, and the Drug Package Insert) as defined in the Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO) standard of care guidelines. Documentation is submitted of the patient s current diagnosis, current body weight, body surface area (needed for Leukine request only) and absolute neutrophil count (within 30 days of the request). Prescribed dosing of medication is within FDA approved indications and/or is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 12 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN or ASCO standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. PA CRITERIA FOR RE-AUTHORIZATION The prescribing physician has provided documentation as to the clinical benefits of the medication supporting continued treatment, OR the medication is being continued in accordance with the recommended time as defined by FDA drug package insert, and/or per recommendations of the medical compendium as described above, and/or per the NCCN or ASCO standard of care guidelines. Documentation is submitted of the patient s absolute neutrophil count (within 30 days of the request). Prescribed dosing of medication is within FDA approved indications and/or supported by the medical compendium as defined by the Social Security Act and/or per the NCCN or ASCO standard of care guidelines. If all of the above conditions are met, the request will be approved for up to 12 weeks or as recommended per FDA approved indications and/or as defined by the medical compendium as defined above and/or per the NCCN or ASCO standard of care guidelines; if all of the above criteria are not met then, based on professional judgment, the Pharmacist reviewer will issue a denial for the medication requested. Medically Accepted Dosing ASCO and NCCN practice guidelines prefer the subcutaneous route of administration for all 3 white blood cell stimulators. Per ASCO guidelines the calculated dose may be rounded off, within reason, to the nearest vial/syringe size to reduce wastage. FDA APPROVED INDICATIONS AND DOSING: Neupogen (filgrastim) Adult dosing: Patients Receiving Myelosuppressive Chemotherapy: The recommended starting dose of Neupogen is 5 mcg/kg/day, administered as a single daily injection SC bolus injection, by short IV infusion (15 to 30 minutes), or by continuous SC or continuous IV infusion. Doses may be increased in increments of 5 mcg/kg for each chemotherapy cycle, according to the duration and severity of the ANC nadir. Therapy with Neupogen should be discontinued if the ANC surpasses 10,000/mm 3 after the expected chemotherapy-induced neutrophil nadir. Cancer Patients Receiving Bone Marrow Transplant (BMT): The recommended dose of Neupogen following BMT is 10 mcg/kg/day given as an IV infusion of 4 to 24 hours, or as a continuous 24 hour SC infusion. The daily dose of Neupogen should be titrated against the neutrophil response as follows: Absolute Neutrophil Count When ANC > 1000/mm 3 for 3 consecutive days Then: If ANC remains > 1000/mm 3 for 3 more consecutive days Neupogen Dose Adjustment Reduce to 5 mcg/kg/day Discontinue Neupogen

Then: If ANC decreases < 1000/mm 3 Resume at 5 mcg/kg/day If ANC decreases to < 1000/mm 3 at any time during the 5 mcg/kg/day administration, Neupogen should be increased to 10 mcg/kg/day, and the above steps should then be followed. Patients with Congenital neutropenia: 6 mcg/kg SC twice daily based on ANC results and clinical course. Patients Undergoing Peripheral Blood Progenitor Cell Collection (PBPC) and Therapy: The recommended dose of Neupogen for the mobilization of PBPC is 10 mcg/kg/day SC, either as a bolus or a continuous infusion. It is recommended that Neupogen be given for at least 4 days before the first leukapharesis procedure and continued until the last leukapharesis. Neupogen dose modification should be considered for those patients who develop a WBC count > 100,000/mm 3. Patients with Severe Chronic Neutropenia, Idiopathic or Cyclic: The recommended daily starting dose is 5 mcg/kg as a single injection SC every day. Pediatric dosing: ASCO has no official recommendation, but states that adult doses have been used in pediatric patients; NCCN has no information on pediatric patients). Based on the Compendia pediatric dosing was available for: Chemotherapy-induced Neutropenia, BMT to reduce the duration of neutropenia and neutropenia-related clinical sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy prior to BMT, Peripheral Blood Progenitor Cell Transplantation; and Congenital, Cyclic and Idiopathic neutropenia. Follow adult dosing guidelines for pediatric dosing for aforementioned indications. Leukine (sargramostim) Adult dosing: Use Following Induction Chemotherapy in Acute Myelogenous Leukemia (AML): The recommended dose is 250 mcg/m 2 /day administered intravenously over a 4 hour period starting approximately on day 11 or four days following the completion of induction chemotherapy. Leukine treatment should be continued until an ANC <1500 cells/mm 3 for 3 consecutive days or a maximum of 42 days. Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progenitor Cells: The recommended dose is 250 mcg/m 2 /day administered IV over 24 hours or SC once daily Leukine treatment should be continued until an ANC >1500 cells/mm 3 for 3 consecutive days Use in Myeloid Reconstitution after Autologous or Allogenic Bone Marrow Transplantation: The recommended dose is 250 mcg/m 2 /day administered IV over a 2 hour period beginning two to four hours after bone marrow infusion and not less than 24 hours after the last dose of chemotherapy or radiotherapy. Leukine treatment should be continued until an ANC >1500 cells/mm 3 for 3 consecutive days. Use in Bone Marrow Transplantation Failure of Engraftment Delay: The recommended dose is 250 mcg/m 2 /dayfor 14 days as a 2 hour IV infusion. The dose can be repeated after 7 days off therapy if engraftment has not occurred. If engraftment still has not occurred, a third course of 500 mcg/m 2 /day administered IV for 14 days may be tried after another 7 days off therapy. If after the third course there is still no improvement, it is unlikely that further dose increases will be beneficial. Pediatric dosing: Safety and efficacy in pediatric patients has not been established; however, available safety data indicate that Leukine does not exhibit any greater toxicity in pediatric patients than in adults. Neulasta (pegfilgrastim) Adult dosing: Chemotherapy-induced Febrile Neutropenia Prophylaxis: The recommended dose of Neulasta is a single SC injection of 6 mg administered once per chemotherapy cycle. Neulasta should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy. Pediatric dosing: Safety and efficacy in pediatric patients have not been established; however the available safety data indicates that Neulasta does not exhibit any great toxicity in pediatric patients than in adults.

References: 1. Leukine Prescribing Information. Berlex. 06/2012. 2. Neulasta Prescribing Information. Amgen Inc. 06/2011. 3. Neupogen Prescribing Information. Amgen Inc. 03/2013. 4. ASCO Guidelines. 2000 Update of Recommendation for the use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Clinical Practice Guidelines. 5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology Myeloid Growth Factors in Cancer Treatment. V 6. Stull DM, Bilmes R, Kim H, Fichtl R. Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm. 2005;62(1):83-87. Revision/Review Date: 06/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

Formulary Status- Non Formulary PRIOR AUTHORIZATION CRITERIA Xolair (omalizumab): 150mg lyophilized powder for injection PA CRITERIA FOR INITIAL APPROVAL: The physician who has requested Xolair is pulmonologist or allergist or documentation (consultation) was submitted with the request indicating that Xolair was recommended by a pulmonologist or allergist. The patient s age is > 12 years old and the patient has a > 1 year history of moderate-to-severe asthma The patient s total serum IgE 30 IU/ml to 700 IU/ml and the prescribed dose is within approved FDA dosing guidelines. The patient has a documented baseline FEV 1 < 80% of predicted or FEV 1/FVC that has been reduced by at least 5% of normal for the patient age range (see Table 1 below). The patient has a documented history of one or more of the following: requires daily use of inhaled short acting B 2 agonists, history of daily or continual asthma symptoms, limited physical activity or activity affected by exacerbations due to asthma, and frequent (> once per week) nighttime symptoms. Documentation that the patient is still having significant symptoms (i.e. hospital admission, emergency room visits, or the severe of asthma exacerbations) while compliant on a high-dose inhaled corticosteroid with a long-acting B 2 agonists + a leukotriene receptor antagonist or theophylline. If the patient utilizing these therapies then the patient must have a documented medical reason for not maximizing both high dose inhaled corticosteroids with long acting bronco dilator medication (e.g. side effects, intolerance, and hypersensitivity). The patient has a positive documented immediate response on RAST test or skin prick test to at least 1 common allergen (e.g. dermatophagoides farinae, dermatophagoides pteronyssinus, dog, cat, or cockroach) and there is documented evidence that the positive skin tested allergen(s) is an asthma trigger either from environmental exposure or from testing or from attempted allergen immunotherapy. Documentation was submitted indicating what environmental measures were attempted to avoid or minimize exposure to identified allergen asthma triggers OR a reason (e.g. unavoidable allergen) for not trying to avoid asthma allergen trigger(s). The patient is not receiving any medication (e.g. Beta Blockers or NSAIDs) that could cause bronchospasm or cause an asthma exacerbation and if the patient is on a potential asthma inducing medication, that there is a documented medical reason for continuing that medication as well as documentation that the medication is not a cause for worsening asthma or causing any asthma symptoms. If all of the above conditions are met, the request will be approved with a 4-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. PA CRITERIA FOR REAUTHORIZATION AFTER 4 MONTHS OF THERAPY: Documentation submitted indicates that the member has significantly clinically benefited from the medication (e.g. patient has marked improvement in pulmonary function tests such as FEV 1 or peak expiratory flow rate, decrease in asthma exacerbations or a decrease in inhaled or oral corticosteroid use since receiving Xolair therapy). The prescribed dose is within approved FDA dosing guidelines. If all of the above conditions are met, the request will be approved with a 6-month duration; if all of the above criteria are not met, the request is referred to a Medical Director for medical necessity review. FDA INDICATION: Xolair is indicated for the treatment of adults and adolescents (> 12 years old) with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. Important Limitations of Use: o Xolair is not indicated for treatment of other allergic conditions o Xolair is not indicated for the relief of acute broncospasm or status asthmatics o Xolair is not indicated for use in pediatric patients less than 12 years of age. DOSAGE AND ADMINITRATION: Pretreatment Serum IgE(IU/ml) Body Weight (Kg) 30-60 >60-70 >70-90 >90-150 30-100 > 100-200 150mg q 4 weeks 150mg q 4 weeks 150mg q 4 weeks 300mg q 4 weeks 300mg q 4 weeks 300mg q 4 weeks 300mg q 4 weeks 225mg q 2 weeks

Pretreatment Serum IgE(IU/ml) Body Weight (Kg) 30-60 >60-70 >70-90 >90-150 > 200-300 300mg q 4 weeks 225 mg q2 weeks 225mg q 2 weeks 300mg q 2 weeks > 300-400 > 400-500 225mg 2 weeks 225mg q 2 weeks 300mg q 2 weeks 300mg q 2 weeks 300mg q 2 weeks 375mg q 2 weeks DO NOT DOSE DO NOT DOSE > 500-600 > 600-700 300mg q 2 weeks 375mg q 2 weeks DO NOT DOSE DO NOT DOSE 375mg q 2 weeks DO NOT DOSE DO NOT DOSE DO NOT DOSE Approved dosing is based on FDA dosing guidelines as summarized in the above chart. However, due to the long half life of the medication and the fact that the medication can be dosed once a month, total monthly doses will be approved in order to prevent wasting of medication due to split vial dosing (i.e. 375 mg every 2 weeks would be approved to be dosed as 450 mg then in 2 weeks 300 mg, i.e. 225 mg q2weeks would be approved 300 mg then in 2 weeks 150 mg in both examples total administered drug is the same, and it benefits the member because they receive one less injection of medication). Table 1: Normal FEV 1/FVC Patients Age: 8 19 y/o 20 39 y/o 40 59 y/o 60 80 y/o Normal Values: 85 % 80 % 75 % 70 % DOSAGE ADJUSTMENTS Total IgE levels are elevated during treatment and remain elevated for up to one year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting less than 1 year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Xolair has been interrupted for one year or more. Doses should be adjusted for significant changes in body weight. GLOSSARY: FEV 1 forced expiratory volume in one second (measured using spirometry) FVC forced vital capacity PEF peak expiratory flow (measured using home peak flow meter) PEFR peak expiratory flow rate REFERENCES: 1. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. The National Heart Lung and Blood Institute. NIH publication. Updated August 2007. Available at http://www.nhlbi.nih.gov/guidelines/. Accessed May 2009. 2. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-ige antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003; 111(1):87-90. 3. Finn A, Gross G, van Bavel J, Lee T, et al. Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol 2003; 111(2):278-284. 4. Pulmonary-Allergy Drugs Advisory Committee. Biologics License Application. (BLA) http://www.fda.gov/ohrms/dockets/ac/cder03.html#pulmonaryallergydrugs 5. Adkinson, NF et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 1997; 336:324-331. 6. Li, James et al. Allergen Immunotherapy: a practice parameter. Annals of Allergy, Asthma, and Immunology 2003; 90:1-40. 7. Ross, RN et al. Effectiveness of a specific immunotherapy in the treatment of asthma: a meta analysis of prospective, randomized, double-blind, placebo controlled studies. Clin Ther 2000; 22:329-341.

8. Cantani, A et al. A three year prospective study of specific immunotherapy to inhalent allergens: evidence of safety and efficacy in 300 children with allergic asthma. J Investig Allergol Clin Immunol 1997; 7:90-97. 9. Xolair Prescribing Information. Genentech, Inc. 07/2010. Revision/Review Date: 06/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Clinical reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ZOFRAN (ondansetron) Tablet: 4mg, 8mg; Orally Disintegrating Tablet: 4mg, 8mg; Solution: 4mg/5ml STATUS: Formulary (generic) ZOFRAN (ondansetron) Tablet: 24mg STATUS: Non-Formulary (generic) PA CRITERIA FOR APPROVAL: CHEMOTHERAPY/RADIATION THERAPY: Diagnosis of cancer chemotherapy or radiation therapy. NOTE: An automatic approval will occur at the point-of-sale if the prescribed quantity does not exceed 90 tablets/ 30 days (4mg, 8mg) or 50ml/ 30 days for the oral solution. NOTE: Zofran 24mg tablets are non-preferred. Requests for the 24mg tablets should be referred to using the 8mg tablets. If the above conditions are met, the request will be approved with limitations for the duration of the chemotherapy or radiation, not to exceed 3 months: 15 tablets/30 days (4mg,8mg) or 50ml/30 days for the oral solution; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. QUANTITIES GREATER THAN ABOVE LIMITS PER 30 DAYS: If the request is for a quantity greater than allowed per 30 days, the request will be referred to a Medical Director for medical necessity review. HYPEREMESIS GRAVIDARUM: Diagnosis of hyperemesis gravidarum. AND Dosage does not exceed 4-8mg every 6 hours. NOTE: An automatic approval will occur at the point-of-sale if the prescribed quantity does not exceed 15 tablets/30 days (4mg, 8mg) or 50ml/30 days for the oral solution. NOTE: Zofran 24mg tablets are non-preferred. Requests for the 24mg tablets should be referred to using the 8mg tablets. If the above conditions are met, the request will be approved for the remaining duration of the pregnancy or the duration requested (whichever is less); if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin >50 mg/m 2. Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen. Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, Zofran Tablets, Zofran Orally Disintegrating Tablets, and Zofran Oral Solution are recommended even where the incidence of postoperative nausea and/or vomiting is low. DOSAGE AND ADMINISTRATION: Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy: The recommended adult oral dosage of Zofran is 24mg given as three 8-mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin >50 mg/m 2. Multiday, single dose administration of a 24mg dosage has not been studied. Pediatric Use: There is no experience with the use of a 24mg dosage in pediatric patients. Geriatric Use: The dosage recommendation is the same as for the general population. Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy: The recommended adult oral dosage is one 8mg Zofran Tablet or one 8mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8mg of ondansetron) of Zofran Oral Solution given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8mg Zofran Tablet or one 8-mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8mg of ondansetron) of Zofran Oral Solution should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use: For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4mg Zofran Tablet or one 4mg Zofran ODT Tablet or 5mL (1 teaspoonful equivalent to 4mg of ondansetron) of Zofran Oral Solution given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4mg Zofran Tablet or one 4mg Zofran ODT Tablet or 5mL (1 teaspoonful equivalent to 4 mg of ondansetron) of Zofran Oral Solution should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy. Geriatric Use: The dosage is the same as for the general population. Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen: The recommended oral dosage is one 8mg Zofran Tablet or one 8mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8mg of ondansetron) of Zofran Oral Solution given 3 times a day. For total body irradiation, one 8mg Zofran Tablet or one 8mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8mg of ondansetron) of Zofran Oral Solution should be administered 1 to 2 hours before each fraction of radiotherapy administered each day. For single high-dose fraction radiotherapy to the abdomen, one 8mg Zofran Tablet or one 8mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8mg of ondansetron) of Zofran Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy. For daily fractionated radiotherapy to the abdomen, one 8mg Zofran Tablet or one 8mg Zofran ODT Tablet or 10mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of Zofran Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given. Pediatric Use: There is no experience with the use of Zofran Tablets, Zofran ODT Tablets, or Zofran Oral Solution in the prevention of radiation-induced nausea and vomiting in pediatric patients. Geriatric Use: The dosage recommendation is the same as for the general population. Postoperative Nausea and Vomiting: The recommended dosage is 16mg given as two 8mg Zofran Tablets or two 8mg Zofran ODT Tablets or 20mL (4 teaspoonfuls equivalent to 16 mg of ondansetron) of Zofran Oral Solution 1 hour before induction of anesthesia. Pediatric Use: There is no experience with the use of Zofran Tablets, Zofran ODT Tablets, or Zofran Oral Solution in the prevention of postoperative nausea and vomiting in pediatric patients. Geriatric Use: The dosage is the same as for the general population. Dosage Adjustment for Patients with Impaired Renal Function: The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron. Dosage Adjustment for Patients with Impaired Hepatic Function: In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8mg should not be exceeded. REFERENCES: 1. Zofran. Prescribing Information. GlaxoSmithKline. May 2010. 2. Coupland NJ, Bailey JE, Potokar JP, et al.5-ht3 receptors, nausea, and serotonin reuptake inhibition.j Clin Psychopharmacol Apr 1997, 17(2) p142-3. 3. Leman P.Utility of ondansetron in children with vomiting. Ann Emerg Med (United States), Sep 2002, 40(3) p366-7. 4. The National Comprehensive Cancer Network (NCCN) and The American Cancer Society (ACS). Nausea and Vomiting. Treatment Guidelines for Patients with Cancer. Version 1. January 2001. 5. Walker PC, Biglin KE, Constance TD, et al. Promoting the use of oral ondansetron in children receiving cancer chemotherapy. Am J Health Syst Pharm (United States), Apr 1 2001, 58(7) p598-602. 6. Facts and Comparisons, St. Louis, 2010 CliniSphere Version ISBN 1-57439-036-8: Record 29901. 7. The Hyperemesis Education & Research Foundation. Treatment Overview of Hyperemesis Gravidarum. Leesberg (VA); August 2006. Review Date: 4/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ZOVIRAX (acyclovir) Cream: 5%, Ointment: 5% STATUS Preferred PA CRITERIA FOR APPROVAL Zovirax Cream: Diagnosis of herpes labialis (cold sores). Documented trial and failure or intolerance to Denavir. Zovirax Ointment: Diagnosis of venereal herpes. Documented trial and failure or intolerance to a preferred oral antiviral. If the above conditions are met, the request will be approved with a 1 month duration; if the above conditions are not met, the request will be referred to a Pharmacist for medical necessity review. FDA INDICATIONS Zovirax Cream: Treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older. Zovirax Ointment: Management of initial genital herpes and in limited non-life-threatening mucocutaneous Herpes simplex virus infections in immunocompromised patients. DOSAGE AND ADMINISTRATION Zovirax Cream: Apply 5 times per day for 4 days. Therapy should be initiated as early as possible following onset of signs and symptoms (i.e., during the prodrome or when lesions appear). Zovirax Ointment: Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying Zovirax to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms. REFERENCES 1. Zovirax Cream. Prescribing Information. GlaxoSmithKline. October 2011. 2. Zovirax Ointment. Prescribing Information. GlaxoSmithKline. August 2011. 3. Facts and Comparisons, St. Louis, 2012 efacts CliniSphere Version ISBN 1-57439-036-8. Revision/Review Date: 7/2013 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Pharmacist reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.

TRUE HEALTH PRIOR AUTHORIZATION CRITERIA ZYVOX (linezolid) Tablet: 600mg; Suspension: 100mg/5mL STATUS: Non-Formulary PA CRITERIA FOR APPROVAL: Diagnosis of vancomycin-resistant enterococcus faecium infection, nosocomial pneumonia, complicated skin and skin structure infection (including diabetic foot infections, without concomitant osteomyelitis), uncomplicated skin and skin structure infection, methicillin-resistant Staphylococcus aureus infection, or community-acquired pneumonia. And patient meets one of the two following criteria: Documented history of treatment with Zyvox IV (continuation of therapy, IV to PO conversion). Documentation that the infection is susceptible to Zyvox AND the patient has failed treatment or is contraindicated to treatment with antibiotics to which the organism is susceptible. If the above conditions are met, the request will be approved with up to a 1 month duration depending on the type of infection; if the above conditions are not met, the request will be referred to a Medical Director for medical necessity review. FDA INDICATIONS: Vancomycin-Resistant Enterococcus Faecium Infections: Including cases with concurrent bacteremia. Nosocomial Pneumonia: Caused by Staphylococcus aureus (methicillin-susceptible and methicillin-resistant strains), or Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]*). Complicated Skin and Skin Structure Infections, Including Diabetic Foot Infections, without Concomitant Osteomyelitis: Caused by Staphylococcus aureus (methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. Zyvox has not been studied in the treatment of decubitus ulcers. Uncomplicated Skin and Skin Structure Infections: Caused by Staphylococcus aureus (methicillin- susceptible only) or Streptococcus pyogenes. Community-Acquired Pneumonia: Caused by Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]*), including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin- susceptible strains only). * MDRSP refers to isolates resistant to two or more of the following antibiotics: penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/sulfamethoxazole. NOTE: Zyvox is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected. NOTE: To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zyvox and other antibacterial drugs, Zyvox should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. DOSAGE AND ADMINISTRATION: Infection Complicated skin and skin structure infections Community-acquired pneumonia, including concurrent bacteremia Nosocomial pneumonia Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia Dosage and Route of Administration Recommended Duration of Pediatric Patients (Birth through Adults and Adolescents (12 Treatment 11 Years of Age) Years and Older) (Consecutive Days) 10mg/kg IV or PO every 8 hours 600mg IV or PO every 12 hours 10-14 10mg/kg IV or PO every 8 hours 600mg IV or PO every 12 hours 14-28 <5 years: 10mg/kg PO every 8 Uncomplicated skin and hours skin structure infections 5-11 years: 10mg/kg PO every 12 hours Adults: 400mg PO every 12 hours Adolescents: 600mg PO every 12 10-14 hours

IV to PO Conversion: Zyvox has approximately 100% bioavailability. For patients who are being converted to the oral formulation, refer to the table below: IV Dose Oral Dose* 10mg/kg every 8 hours 10mg/kg every 8 hours 10mg/kg every 12 hours 10mg/kg every 12 hours 400mg every 12 hours 400mg every 12 hours 600mg every 12 hours 600mg every 12 hours *Oral dosing using either oral suspension or tablets. REFERENCES: 1. Facts and Comparisons, St. Louis, efacts 2011 CliniSphere Version ISBN 1-57439-036-8. 2. Zyvox. Prescribing Information. Pfizer, Inc. August 2011. 3. Stevens, Dennis, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections. Clinical Infectious Diseases. 2005; 41:1373-406. 4. McAuley D. Zyvox - Prescribing information. Updated 08/10/2011. Review Date: 7/2012 Associated Policy: Prior Authorization of Medications 236.200 NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the requested item is medically necessary.