PHARMACY PRIOR AUTHORIZATION



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PHARMACY PRIOR AUTHORIZATION Hepatitis C Clinical Guideline Harvoni (sofosbuvir/ledipasvir), Sovaldi (sofosbuvir), Viekira PAK (ombitsavir, paritapravir/ritonavir, dasubavir), and Olysio (simeprevir) Authorization Guidelines: For patients who meet all of the following (with submitted charts notes and lab results): 18 years of age or older Chronic Hepatitis C genotype 1, 2, 3, or 4 Prescribed by a physician specializing in infectious disease, HIV, gastroenterology, hepatology, or transplant Abstinence from alcohol or illicit drug use for at least 6 months and the member is compliant with a drug and alcohol dependency treatment Baseline HCV-RNA within the last 3 months Evidence of stage 3 or stage 4 hepatic fibrosis or cirrhosis as evidenced by one of the following: o Metavir- F3 o FibroSure- 0.58 o Fibroscan (transient elastography) - 9.5 kpa o APRI score- > 1.5 OR Radiological imaging consistent with cirrhosis (i.e., evidence of portal hypertension) OR patient has serious extrahepatic manifestations of HCV infection (i.e., leukocytoclastic vasculitis, membranoproliferative glomerulonephritis, or symptomatic cryoglobulinemia) Current treatment plan (see Monitoring) Criteria for Approval: Harvoni (ledipasvir/sofosbuvir) genotype 1: Treatment Naïve: o With cirrhosis; maximum treatment duration 12 weeks OR o Without cirrhosis and pre-treatment HCV-RNA > 6 million IU/mL; maximum treatment duration 12 weeks OR o Without cirrhosis and pre-treatment HCV-RNA < 6 million IU/mL; maximum treatment duration 8 weeks Treatment Experienced (previous trial of Peg-IFN/RBV ± Protease inhibitor): o Without cirrhosis; maximum treatment duration 12 weeks OR o With cirrhosis; Harvoni + ribavirin, maximum treatment duration 12 weeks 1

Harvoni Treatment Table: Patient Population Treatment Duration of treatment Treatment naïve without cirrhosis Harvoni 8 weeks HCV RNA < 6 million IU/mL Treatment naïve with or without Harvoni 12 weeks cirrhosis, HCV RNA > 6 million IU/mL Treatment-experienced**without Harvoni 12 weeks cirrhosis Treatment-experienced** with cirrhosis Harvoni + ribavirin 12 weeks *8 weeks of treatment can be considered in treatment naive patients without cirrhosis who have pretreatment HCV RNA levels less than 6 million IU/mL. **Treatment experienced patients include patients who have failed treatment with either peginterferon alpha + ribavirin or an HCV protease inhibitor + peginterferon alpha + ribavirin Viekira Pak (ombitasvir, paritaprevir/ritonavir, dasubavir) genotype 1a or 1b: HCV monotherapy or HCV/HIV co-infection (genotype 1a) : o Without cirrhosis; treatment naïve or treatment experienced with Peg-IFN and ribavirin maximum treatment duration 12 weeks OR o With cirrhosis; treatment naïve or treatment experienced with Peg-IFN and ribavirin; maximum treatment duration 24 weeks HCV monotherapy or HCV/HIV co-infection (genotype 1b) : o With or without cirrhosis; treatment naïve or treatment experienced with Peg-IFN and ribavirin; maximum treatment duration 12 weeks Post Transplantation (Metavir F2) HCV monotherapy or HCV/HIV co-infection (genotype 1a or 1b) : o maximum treatment duration 24 weeks Viekira Pak treatment table: Patient Population Treatment Duration of Treatment Genotype 1a without cirrhosis Viekira PAK + ribavirin 12 weeks Genotype 1a with cirrhosis Viekira PAK + ribavirin 24 weeks Genotype 1b without cirrhosis Viekira PAK 12 weeks Genotype 1b with cirrhosis Viekira PAK + ribavirin 12 weeks * For HIV Co-infection: patient must be on HIV antiretroviral medications before initiating treatment with Viekira 2

Sovaldi (sofosbuvir) genotypes 2, 3, or 4: HCV monotherapy or HCV/HIV co-infection (genotype 2) : Sovaldi and ribavirin cirrhosis including HCC; maximum duration of treatment 12 weeks HCV monotherapy or HCV/HIV co-infection (genotype 3): Sovaldi, Peg-IFN, and ribavirin cirrhosis including HCC; maximum duration of treatment 12 weeks OR Sovaldi and ribavirin (Peg-IFN ineligible) cirrhosis including HCC; maximum duration of treatment 24 weeks HCV monotherapy or HCV/HIV co-infection (genotype 4): Sovaldi, Peg-IFN, and ribavirin cirrhosis including HCC; maximum duration of treatment 12 weeks OR Sovaldi and ribavirin (Peg-IFN ineligible) cirrhosis including HCC; maximum duration of treatment 24 weeks Hepatocellular Carcinoma (awaiting transplantation): Sovaldi and ribavirin o Not previously transplanted AND o Must meet Milan criteria (defined as the presence of tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than 3 tumor nodules, each 3 cm or less in diameter in patients with multiple tumors and no extra hepatic manifestations or evidence of vascular invasions of tumor) o Maximum duration of treatment 48 weeks Sovaldi treatment table: Patient population Treatment Duration of Treatment HCV monotherapy or HCV/HIV co-infection Genotype 2 Sovaldi + ribavirin 12 weeks Genotype 3 Sovaldi + Peg-IFN + ribavirin 12 weeks OR Sovaldi + ribavirin 24 weeks (peg ineligible) Genotype 4 Sovaldi + Peg IFN + ribavirin Sovaldi + ribavirin 12 weeks OR 24 weeks (peg ineligible) Hepatocellular Carcinoma (HCC) Sovaldi + ribavirin For up to 48 weeks or until liver transplantation Sovaldi/Olysio combination (simeprevir/sofosbuvir) genotype 1: Case by case basis 3

Olysio (simeprevir) genotype 1a or 1b: For HCV genotype 1b; or 1a where negative for NS3 Q80K polymorphism; Will be used with RBV and PEG interferon and does not have a contraindication or intolerance to RBV or PEG Will not be used in combination with Sovaldi, in conditions others then those specifically outlined above. Has not previously failed treatment with Protease Inhibitors (Incivek or Victrelis) HCV-RNA will be monitored at TW4, 12 and 24 (if applicable) Olyiso treatment table Treatment naïve and prior relapse patients including those with cirrhosis Prior non-responder patients (including partial and null responders) including those with cirrhosis Triple therapy Dual therapy Total treatment (Olysio, peg + rbv) (peg + rbv) duration First 12 weeks Additional 12 weeks 24 weeks First 12 weeks Additional 36 weeks 48 weeks Olysio Stopping Rules: Treatment Stopping Rules in any patient with inadequate On-Treatment Virologic Response HCV-RNA Action Treatment Week 4: greater than or equal to 25 Discontinue Olysio, Peginterferon alfa and ribavirin IU/ml Treatment Week 12: greater than or equal to 25 Discontinue Olysio, Peginterferon alfa and ribavirin IU/ml (treatment with Olysio is complete at Week 12) Treatment Week 24: greater than or equal to 25 Discontinue Peginterferon alfa and ribavirin IU/ml Monitoring: Provider agrees to submit HCV-RNA at treatment week 4, 12, and 3 months post treatment ( SVR 12) Member understands treatment regimen and agrees to remain compliant and adherent during the full course of therapy Initial Authorization: Approval Duration o 8 weeks o 6 weeks (for 8 week regimens only) Reauthorization: 4

HCV-RNA lab results to support > 2 log-10 drop at treatment week 4 Non-Coverage Criteria: Previous trial or failure of sofosbuvir or simeprevir History of non-compliance with previous Hep C treatment Decompensated liver disease or decompensated cirrhosis For combination treatments including ribavirin-current pregnancy egfr < 30 ml/min/1.73m 2 or ESRD on hemodialysis Coverage for greater than the duration of treatment outlined above Coverage limited to once per lifetime, unless determined by the Medical Director to be medically necessary due to extenuating circumstances Lost or Stolen medication Fraudulent use Will not be used in combination with the following medications (i.e, carbamazepine, phenytoin Phenobarbital, oxcarbazepine, St John s wort, rifampin, tipranavir/ritonavir) Not used concomitantly with other protease inhibitors or DAA (i.e., Sovaldi, Olysio, Victrelis, Incivek) Lifetime expectancy for less than 12 months due to non-liver related comorbid conditions For Viekira Pak regimens: it will not be taken with alfuzosin HCL, carbamazepine, phenytoin, phenobarbital, gemfibrozil, rifampin, ergotamine, dihydroergotamine, ergonovine, methylergonovine, ethinyl estradiol-containing medications such as combined oral contraceptives, St. John s Wort, lovastatin, simvastatin, pimozide, efavirenz, sildenafil when dosed as Revatio for the treatment of pulmonary arterial hypertension, triazolam, and orally administered midazolam Non-FDA approved indications, which are not listed in Criteria for Approval section, unless there is sufficient documentation of efficacy and safety in the published literature 5

Additional Information: Interferon Ineligible Criteria: a) Autoimmune hepatitis or other autoimmune disorders b) Thrombocytopenia c) Previous intolerance to IFN leading to treatment discontinuation* d) Pre-existing hematological disease as evidenced by: i) Baseline neutrophil count < 1500/µL, and ii) Baseline platelet count < 90,000/µL, and iii) Baseline hemoglobin of < 10 g/dl e) History of psychiatric disorders: i) Schizophrenia ii) Bipolar Disorder iii) Previous inpatient psychiatric admission iv) History of a suicide attempt within the past 2 years v) Unstable depression evidenced by a psychiatrist s consult f) Decompensated Liver disease Case Management: For plans that support HCV the following will be required: Patient and prescriber agree to participate with nursing & pharmacy case management of the plan to assure patient compliance with the prescribed medication, access to services, lab tests, lab reviews and offer medical guidance as needed to optimize a successful outcome for the patient. Response Defintions: Partial Responder: Member experiences at least a 2-log10 (100 times) drop in HCV RNA, but has the inability to fully remove the virus from the blood by end of treatment. Null/Non Responder: Member does not experience at least 2-log10 (100 times) drop in HCV RNA 8-12 weeks of treatment. Relapser: Member has an undectectable HCV viral load at end of treatment regimen, but who has a dectectable viral load within 12-24 weeks after stopping treatment. 6

References: 1. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C.http://www.hcvguidelines.org/full-report-view. Accessed 01/22/2015. 2. Harvoni [Prescribing Information]. Foster City, CA: Gilead Sciences, Inc.; October 2014 3. Gold Standard, Inc. Harvoni. Clinical pharmacology [database online] Available at http://www.clinicalpharmacology.com Accessed Jan 22, 2015. 4. Gold Standard, Inc. Viekira Pak. Clinical pharmacology [database online] Available at http://www.clinicalpharmacology.com Accessed Jan 22, 2015. 5. Gold Standard, Inc. Olysio. Clinical pharmacology [database online] Available at http://www.clinicalpharmacology.com Accessed Jan 22, 2015. 6. Sovaldi [Prescribing Information]. Foster City, CA: Gilead Sciencs, Inc.; Dec 2013 7. Viekira PAK [Prescribing Information]. North Chicago, Ill: AbbVie, Inc.; Dec 2014 8. Olysio [Prescribing Information]. Titusville, NJ: Jansen.; Nov 2014 7