Prior Authorization Guideline

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1 Prior Authorization Guideline Guideline: MEDPD SPAP Inj - Botox Therapeutic Class: Musculoskeletal Agents Therapeutic Sub-Class: Musculoskeletal Relaxant Agents Client: PDP SPAP Inj Approval Date: 3/17/2000 Revision Date: 4/4/2006 I. BENEFIT COVERAGE Table 1. Formulary status Non-Formulary Products Tier 5 Botox (Botulinum Toxin Type A) Formulary Products II. INDICATIONS A. FDA Approved Indications 1 1. Botox is indicated for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. 2. Botox is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents. 3. Botox is indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders (involving muscles of the face) in patients 12 years of age and above. B. Non-FDA Approved Indications 2, 3 1. Botox has been used in the treatment of migraine and tension-type headaches, achalasia, chronic anal fissures, dynamic muscle contracture in pediatric cerebral palsy patients, muscle spasticity as a result of CNS disorder or CNS injury, and oromandibular dystonia. III. GUIDELINE A. Neuromuscular Disorders 4-6

2 1. Botox will be approved in patients based on one of the following criteria: a. Strabismus and blepharospasm associated with dystonia b. Benign essential blepharospasm c. VII cranial nerve disorders (hemifacial spasms) in patients 12 years of age or older d. Synkinetic closure of the eyelid associated with VII cranial nerve aberrant regeneration e. Cervical dystonia f. Spasmodic dysphonia g. Spastic torticollis h. Dynamic muscle contracture in pediatric cerebral palsy patients i. Treatment of muscle spasticity as a result of CNS disorder or CNS injury j. Oromandibular dystonia Authorization for therapy will be issued for 6 months. B. Hyperhidrosis (axillary) 1. Initial Therapy a. Botox will be approved in patients based on all of the following criteria: 1. Diagnosis of primary axillary hyperhidrosis 2. One of the following: (1) Score of 3 or 4 on the Hyperhidrosis Disease Severity Scale (HDSS) a,1,7 -OR- (2) Skin maceration with secondary infection 8 3. History of failure, intolerance, or contraindication to topical prescription strength drying agents: Drysol, aluminum chloride hexahydrate b. Authorization for therapy will be issued for one time. 2. Retreatment a. Botox will be approved for retreatment of axillary hyperhidrosis based on both of the following criteria: 1,7 (1) At least a 2-point improvement in HDSS (2) At least 4 to 6 months have elapsed since the last series of injections Authorization for therapy will be issued for one time. C. Migraines/Headache 1. Initial therapy

3 a. Botox will be approved for migraines and headaches based on all of the following criteria: (1) Prescribed by a neurologist or pain specialist (2) Failure, contraindication or intolerance to 5-HT 1 receptor agonists (triptans), or requires greater than the following quantities of triptans per month: Axert tablets Imitrex tablets Imitrex nasal spray Maxalt-MLT tablets Relpax tablets Zomig tablets Zomig-ZMT tablets Zomig Nasal Spray 6 tablets (6.25 mg or 12.5 mg) 9 tablets (25 mg, 50 mg, 100 mg) 6 unit dose devices (5 mg or 20 mg) 9 tablets (5 mg, 10 mg) 6 tablets (20 mg or 40 mg) 12 tablets (2.5 mg) 9 tablets (5 mg) 12 tablets (2.5 mg) 9 tablets (5 mg) 6 unit dose devices (5 mg) (3) Failure or contraindication to prophylactic therapy with at least two of the following agents: Beta-blockers (e.g., propranolol) Tricyclic antidepressants (amitriptyline) Calcium-channel blockers (verapamil) Cyproheptadine Depakote /Depakote ER (divalproex sodium) Topamax (topiramate) (4) Submission of chart notes documenting complete evaluation of the patient. This may include, but is not limited to, the nature, frequency and duration of headache, length of disease, and medication use history. Authorization will be issued for 6 months. b 2. Retreatment a. Botox will be approved for retreatment based on both of the following criteria: (1) Reduction of headache frequency and intensity

4 D. Achalasia (2) Submission of chart notes documenting decreased utilization of pain medications, (eg, narcotic analgesics, NSAIDs) or triptans, or a reduction in the number of emergency room visits. Reauthorization of therapy will be issued for 6 months. 1. Initial therapy a. Botox will be approved for the treatment of achalasia based on one of the following criteria: 12,13 (1) High risk of complication from pneumatic dilation or surgical myotomy -OR- (2) Failure to prior pneumatic dilation or surgical myotomy -OR- (3) Prior dilation caused esophageal perforation -OR- (4) Patient has an epiphrenic diverticulum or hiatal hernia, both of which increase the risk of dilation-induced perforation Authorization will be issued for 6 months. 2. Retreatment b. Botox will be approved for retreatment based on both of the following criteria: (1) Documentation of improvement or reduction in symptoms of achalasia (ie, dysphagia, regurgitation, chest pain) (2) At least 4 to 6 months have elapsed since the last series of injections. c b.reauthorization of therapy will be issued for 6 months. E. Chronic anal fissure 1. Initial therapy a. Botox will be approved for the treatment of chronic anal fissure based on all of the following criteria: 14,15 (1) Diagnosis of chronic anal fissure (2) Failure of two or more of the following conventional therapies

5 (a) Bulk forming laxative (b) Sitz baths (c) Emollient suppositories (d) Topical analgesics (e) Topical nitrates (f) Oral or topical calcium channel blockers Authorization will be issued for 6 months 2. Retreatment a. Botox will be approved for retreatment based on all of the following criteria: (1) Incomplete healing of fissure or recurrence of fissure (2) Improved symptoms with prior treatment with Botox (3) At least 4 to 6 months has elapsed since the last series of injections Reauthorization of therapy will be issued for 6 months. IV. CONTRAINDICATIONS AND WARNINGS A. Contraindications Botox is contraindicated in the presence of infection at the proposed injection sites and in individuals with known hypersensitivity to any ingredients in the formulation. B. Warnings 1. Hypersensitivity reactions Serious and/or immediate hypersensitivity reactions have been rarely reported. These reactions include anaphylaxis, urticaria, soft tissue edema, and dyspnea. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined. If such a reaction occurs further injection of Botox should be discontinued and appropriate medical therapy immediately instituted. 2. Pre-existing neuromuscular disorders Individuals with peripheral motor neuropathic diseases (eg, amyotrophic lateral sclerosis, or motor neuropathy) or neuromuscular junctional disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should only receive Botox with caution. Patients with neuromuscular disorders may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of Botox. Published medical literature has reported rare cases of administration of a botulinum

6 toxin to patients with known or unrecognized neuromuscular disorders where the patients have shown extreme sensitivity to the systemic effects of typical clinical doses. In some of these cases, dysphagia has lasted several months and required placement of a gastric feeding tube. 3. Dysphagia Dysphagia is a commonly reported adverse event following treatment of cervical dystonia patients with all botulinum toxins. In these patients, there are reports of rare cases of dysphagia severe enough to warrant the insertion of a gastric feeding tube. There are also rare case reports where subsequent to the finding of dysphagia a patient developed aspiration pneumonia and died. V. DOSING Neuromuscular Disorders Botox treatment may involve injections more than one site or muscle, and it may be necessary to repeat this treatment every 3 to 6 months. The full effect of the toxin is apparent in 4 to 7 days after the injection and can last from 2 to 6 months. Disorder Target Muscle Dose (Units) Cervical Dystonia Rotatory: Contralateral sternomastoid Ipsilateral Splenius capitis Blepharospasm Strabismus Laterocollis: Ipsilateral sternomastoid Ipsilateral splenius capitis Ipsilateral trapezius Retrocollis: Right splenius capitis Left splenius capitis Right upper trapezius Left upper trapezius Antercollis: Right sternomastoid Left sternomastoid Shoulder elevation: Ipsilateral trapezius Levator scapulae Orbicularis oculi: Conventional technique Pretarsal technique For vertical muscles, and for horizontal strabismus of less than 20 prism diopters, dose in any one muscle Horizontal strabismus of 20 to 50 prism diopters, dose in any one muscle

7 Persistent VI nerve palsy of one month or longer duration, dose in the medial rectus muscle Oromandibular Dystonia Laryngeal Dystonia Adductor type Abductor type Hemifacial Spasm Maximum recommended dose as a single injection for any one muscle for residual or recurrent strabismus should not exceed 25 Units Masseter, perioral Submental muscle complex In each vocalis muscle complex Posterior cryoarhthenoid muscle (only one side) Orbicularis oculi Lower Facial muscles Apraxia of eyelid opening Pretarsal orb. oculi 5-10 Upper Limb Dystonia Flexor pollicis longus 8-15 Flexor carpi radialis Extensor indicis proprius 3-8 Extensor digitorum communis Thenar muscles 3-8 Abductor digiti minimi 5-15 Biceps brachii Brachioradialis Essential Tremor Arms and hands: Each forearm-involved muscle Head: Cervical muscles (total dose) Primary Axillary Hyperhidrosis Recommended Dose: 50 units per axilla The hyperhidrotic area to be injected should be defined using standard staining techniques (eg, Minor's Iodine-Starch Test). After reconstitution, using a 30 gauge needle, 50 units of Botox (2mL) is injected intradermally in 0.1 to 0.2 ml aliquots to each axilla evenly distributed in multiple sites (10-15) approximately 1-2 cm apart. VI. AVAILABILITY Single use vial containing 100 Units of vacuum-dried Clostridium botulinum type A neurotoxin complex VII. BACKGROUND A. Description Botox blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine.

8 B. Clinical Studies Botulinum toxin type A was approved by the FDA for the treatment of strabismus partly on the basis of an open-label trial in which 667 patients received one or more injections. Eye alignment was improved in 367 (55%) of these patients when they were evaluated six months or more after treatment. 1 Botulinum toxin type A has been injected into the periocular muscles and the facial muscles on the affected side of the face in patients with hemifacial spasm. Fifty (86%) of 58 patients with hemifacial spasm reported excellent improvement after receiving botulinum toxin type A injections. Another 4 (7%) patients reported moderate improvement. 16,17 Injection of small doses of botulinum toxin type A into the periocular muscles has led to dramatic improvement in blepharospasm (ie, reduction in eyelid twitching and spasm). In 22 adults with blepharospasm who received botulinum toxin type A injections, excellent improvement (ie, reduction) in spasm intensity was reported by 18 (82%) patients and moderate improvement was reported by 2 patients (9%). 17 Rapid relief of spasm was reported after botulin toxin type A injection in 26 patients with blepharospasm or hemifacial spasm and an inadequate response to medications or surgery. The benefit lasted for weeks to months. There were no major adverse effects. 18 In a randomized, double-blind, placebo-controlled, crossover study, 23 adults with cervical dystonia received the first of two sets of intramuscular injections of botulinum toxin type A 100 Units or placebo followed three months later by the other set of injections. 19 In the 18 patients who completed the study, significant improvement occurred after the botulinum toxin injections, beginning one week after treatment and lasting for about nine weeks. In the 10 patients with neck pain, satisfactory relief was provided by botulinum toxin in nine patients. There were no serious adverse effects. Botulinum toxin type A was approved by the FDA for the treatment of cervical dystonia partly on the basis of a phase III randomized, double-blind, placebo-controlled study of 170 adults with the disorder. 1 A mean total dose of 236 Units of botulinum toxin type A was divided among two to five affected muscles in the 88 patients in the active treatment group. Six weeks after the injections, the severity of abnormal head position and pain intensity and frequency were reduced in the botulinum toxin group but not in the placebo group. There was improvement in the physician global assessment of the patient s status in 51% of patients in the botulinum toxin group and 31% of patients in the placebo group. Laryngeal dystonia (spasmodic dysphonia) is characterized by involuntary spasm of the vocal cords, resulting in abnormal sound when a person attempts to speak or sing. Periodic injections of botulinum toxin type A into the vocal cords in more than 900 patients with spasmodic dysphonia restored an average of 67 to 90% of normal voice function for 11 to 15 weeks. 20 Botulinum toxin type A has been used extensively in children with spasticity due to cerebral palsy Botulinum toxin type A was approved by the FDA for the treatment of severe primary axillary hyperhidrosis partly on the basis of two randomized, double-blind, placebocontrolled trials. 1,26 In one of these studies, 320 patients with bilateral primary axillary hyperhidrosis severe enough to interfere with daily living were randomized to received botulinum toxin type A 50 Units or placebo by intradermal injection in each axilla. A treatment response was defined as a reduction from baseline in axillary sweating by at least 50%. The response rate four weeks after treatment was significantly higher in the botulinum

9 toxin type A group (94%) than in the placebo group (36%). The response rates 16 weeks after treatment were 82% and 21% respectively. A similar response rate was observed in the other randomized, double-blind, placebo-controlled study which involved 322 patients with primary axillary hyperhidrosis, two different intradermal botulinum toxin type A dosages (50 and 75 Units), and if needed, repeat injections no sooner than eight weeks after the initial injection. 1 There was no significant difference between the two dosages in response rate. The median duration of response after the initial treatment was 201 days. The first prospective, randomized, double-blind, placebo-controlled trial of botulinum toxin type A for treating migraine headache involved 123 adults with two to eight moderate-tosevere attacks of migraine headache with or without aura per month. 27 One of two botulinum toxin type A doses (25 Units or 75 Units) or placebo (0.9% sodium chloride) was injected into the pericranial muscles in the forehead. Subjects were followed for three months. Subjects receiving 25 Units of botulinum toxin type A experienced significantly fewer moderate-to-severe migraine attacks per month than subjects in the placebo group. A doseresponse relationship was not observed for botulinum toxin type A. There was no significant difference between the subjects receiving botulinum toxin type A 75 Units and subjects receiving placebo in the frequency of moderate-to-severe headache. Reductions in migraine severity, use of migraine abortive medications, and the frequency of migraine-associated vomiting were associated with treatment with the 25-Unit dose of botulinum toxin. The efficacy of botulinum toxin type A in treating chronic tension-type or migraine headache was evaluated in a randomized, double-blind, placebo-controlled, parallel-group study of 60 adults who experienced headaches more than 15 days each month. 28 Each of the two treatment groups had 23 patients with chronic migraine headache and 7 patients with chronic tension-type headache. Patients were randomized to receive botulinum toxin type A (200 Units) or placebo by injection using a follow the pain strategy to select injection sites on the basis of locations where pain or tenderness was reported (ie, trigger point injections). All patients were offered botulinum toxin type A 200 Units on an open-label basis 12 weeks after the initial treatment and were followed for an additional 12 weeks. Compared with placebo, the number of days with headache decreased significantly in the botulinum toxin group between week 8 and week 12 after the initial treatment. The reduction in the number of days with headache over the 12-week (i.e., 84-day) period after treatment was greater in the botulinum toxin group (33 days) than in the placebo group (24 days), although the difference was not significant. The patients global impressions and change in headache impressions and the investigators global impressions all improved to a significantly greater extent in the botulinum toxin group than in the placebo group. The number of abortive headache medications used were lower in the botulinum toxin group (106 medications) than in the placebo group (135 medications), but the difference was not significant. There was no change in measures of pain on palpation of the head, depression, or psychosocial adjustment to illness. The injections were well tolerated, with mild adverse effects and no significant difference in the frequency of adverse effects between the two groups. The number of days with headache over the 12-week open-label period from week 13 to week 24 was significantly less in the 26 patients who had received two botulinum toxin injections than in the 25 patients who had received only one injection. These findings suggest the potential for a cumulative benefit from repeat botulinum toxin type A injections. The efficacy of intrasphincteric injection of botulinum toxin type A (50 Units, 100 Units, or 200 Units) was evaluated in 118 patients with esophageal achalasia in a randomized trial. 29 Patients rated the frequency of dysphagia, regurgitation, and chest pain on a four-point scale from zero for never to three for daily. A response was defined as a symptom score of two (more than once a week) or less. The treatment response rate 30 days after injection was 82%. The patients who received a 100-Unit dose were given a second dose 30 days after the first dose. Relapse of symptoms occurred after a mean follow-up time of 12 months after the initial dose in 19% of patients who received two 100-Unit injections, 47% of patients in the 50-Unit dose group, and 43% of patients in the 200-Unit dose group.

10 Fifty adults with chronic anal fissure were randomized to receive 20 Units of botulinum toxin by intramuscular injection into the internal anal sphincter or apply 0.2% nitroglycerin ointment twice daily for six weeks. 30 Healing had occurred after two months in 24 (96%) of the 25 patients in the botulinum-toxin group and in 15 (60%) of the 25 patients in the nitroglycerin group, a difference that is significant. One patient in the botulinum toxin group and nine patients in the nitroglycerin group without healing crossed over to the other treatment, and healing subsequently occurred in all 10 of these patients. There were no relapses during an average follow-up time of about 15 months. Moderate-to-severe headache was reported by 5 (20%) of the 25 patients in the nitroglycerin group. No adverse effects were reported by patients in the botulinum toxin group. The efficacy of intrasphincteric injection of botulinum toxin type A (20 to 30 Units) was compared with that of surgery (sphincterectomy) in a randomized, controlled study of 111 patients with chronic anal fissure. 31 Complete healing occurred within two months in 45 (74%) of 61 botulinum toxin-treated patients and 49 (98%) of 50 surgical patients. Ten (63%) of the 16 patients without healing after a single botulinum toxin type A injection were treated with a second injection (the other six patients refused further treatment), resulting in an overall healing rate of 87% (53 of 61 patients) at six months in the botulinum toxin group. Two patients in the surgical group developed recurrences within six months, so the healing rates were comparable in the two groups after six months. After 12 months had elapsed, seven botulinum toxin-treated patients had experienced recurrences, reducing the healing rate to 75%. This rate is significantly lower than the healing rate after 12 months in the surgical patients (94%). However, surgery was associated with a significantly higher rate of complications than botulinum toxin; there were eight cases of anal incontinence in the surgical group and no complications in the botulinum toxin group. A full return to daily activities took significantly less time in the botulinum toxin group than in the surgical group. C. National Guidelines 1. American College of Gastroenterology 12 (1999) a. Although there is no cure for achalasia, the goal of treatment should be relief of patient symptoms and improved esophageal emptying. The two most effective treatment options are graded pneumatic dilation and surgical myotomy. For patients who are at high risk for pneumatic dilation or surgery, endoscopic injection of the LES with botulinum toxin or pharmacological treatment with nitrates or calcium channel blockers may be acceptable alternatives. b. Available data indicate that botulinum toxin is effective in relieving symptoms initially in about 85% of patients. However, symptoms recur in more than 50% of patients within 6 months possibly because of regeneration of the affected receptors. Older patients (>60 yr) and those with vigorous achalasia, defined as esophageal amplitude.40 mm Hg, are more likely to have a sustaned response (up to 1.5 yr) to botulinum toxin injection. In those responding to the first injection, 76% will respond to a second botulinum toxin injection with decreasing response to further injections, usually from antibody formation to this foreign protein. Less than 20% of patients failing to respond to the first injection will respond to a second injection of botulinum toxin. Studies have shown that botulinum toxin is less effective than pneumatic dilation long term. Additionally, some reports indicate that cardiomyotomy may be more difficult and less effective in patients who were previously treated with repeated botulinum toxin injections, possibly because of submucosal scar formation in the esophagus at the site of injection. Finally, the long-term safety of repeated injections of botulinum toxin in achalasia patients is unknown. Therefore, botulinum

11 toxin injection should be reserved for elderly patients or patients who are at high surgical risk or refuse pneumatic dilation and surgical myotomy. 2. American Gastroenterological Association 14 (2003) a. Presently, topical therapy and BT injection should be considered acceptable options, even if not entirely proven, for the treatment of anal fissure. Their low morbidity profiles allow them to be used as first-line treatment, not merely as salvage treatment for failed conservative care. However, further experience will be necessary to determine their definitive role in the algorithm of fissure therapy. VIII. REFERENCES 1. Botox Prescribing Information. Allergan, Inc. October, McEvoy GK. AHFS Drug Information Bethesda, MD: American Society of Health- System Pharmacists, Inc; United States Pharmacopeia Dispensing Information: Drug Information for the Health Care Professional. 25 th ed. Greenwood Village, CO:Thomson MICROMEDEX; American Academy of Neurology (AAN). Training guidelines for the use of botulinum toxin for the treatment of neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1994;44: American Academy of Neurology: Assessment: the clinical usefulness of botulinum toxin-a in treating neurologic disorders. Report of the Therapeutics and Technology Subcommittee of the American Academy of Neurology. Neurology. 1990;40: Charles PD. Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses. Am J Health Syst Pharm. 2004;61:S Lowe NJ, Glaser D, The North American BOTOX in Primary Axillary Hyperhidrosis Clinical Study Group. J Am Acad Dermatol. 2004;50:P50 ABS P Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ. 2001;323: Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.Headache. 2000;40: Ondo WG, Vuong KD, Derman HS. Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia. 2004;24: Dodick DW, Mauskop A, Elkind AH, DeGryse R, Brin MF, Silberstein SD; BOTOX CDH Study Group. Botulinum toxin type a for the prophylaxis of chronic daily headache: subgroup analysis of patients not receiving other prophylactic medications: a randomized double-blind, placebo-controlled study. Headache. 2005;45: Vaezi MF, Richter JE for the American College of Gastroenterology Practice Parameter Committee. Diagnosis and management of achalasia. Am J Gastroenterol. 1999;94: Pasricha PJ, et al. Intrasphincteric botulinum toxin for the treatment of achalasia. N Engl J Med. 1995;332: American Gastroenterological Association. American Gastroenterological Association medical position statement: Diagnosis and care of patients with anal fissure. Gastroenterology. 2003;123: Brisinda G, et al. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. New England Journal of Medicine 1999;341(2): Charles D. Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses. Am J Health-Syst Pharm. 2004;61:S Chang LB, Tsai CP, Liao KK et al. Use of botulinum toxin A in the treatment of hemifacial spasm and blepharospasm. Zhonghua Yi Xue Za Zhi (Taipei). 1999;62:1-5.

12 18. Arthurs B, Flanders M, Codere F et al. Treatment of blepharospasm with medication, surgery and type A botulinum toxin. Can J Ophthalmol. 1987;22: Lu CS, Chen RS, Tsai CH. Double-blind, placebo-controlled study of botulinum toxin injections in the treatment of cervical dystonia. J Formos Med Assoc. 1995;94: Blitzer A, Brin MF, Steward CF. Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year experience in more than 900 patients. Laryngoscope. 1998;108: Koman LA, Mooney JF III, Smith BP, et al. Management of spasticity in cerebral palsy with botulinum-a toxin: report of a preliminary, randomized, double-blind trial. J Pediatr Orthop. 1994;14: Wissel J, Heinen F, Schenkel A et al. Botulinum toxin A in the management of spastic gait disorderes in children and young adults with cerebral palsy: a randomized, double-blind study of high-dose versus low-dose treatment. Neuropediatrics. 1999;30: Sutherland DH, Jaufman KR, Wyatt MP et al. Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture. 1999;10: Koman LA, Mooney JF III, Smith BP et al. BOTOX Study Group. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. J Pediatr Orthop. 2000;20: Fehlings D, Rang M, Glazier J et al. An evaluation of botulinum-a toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. 26. Naumann M, Lowe NJ. Botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis: randomized, parallel group, double blind, placebo controlled trial. BMJ. 2001;323: Silberstein S, Mathew N, Saper J, et al. BOTOX Migraine Clinical Research Group. Botulinum toxin type A as a migraine preventive treatment. Headache. 2000; 40: Ondo WG, Vuong KD, Derman HS. Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia. 2004;24: Annese V, Bassotti G, Coccia G, et al. GIS-MAD Achalasia Study Group. A multi-centre randomized study of intrasphincteric botulinum toxin in patients with oesophageal achalasia. Gut. 2000;46: Brisinda G, Maria G, Bentivoglio AR, et al. A comparison of injections of botulinum toxin injection and lateral sphincterotomy for the treatment of chronic anal fissure.n Engl J Med. 1999;341: Mentes BB, Irkorucu O, Akin M, et al. Comparison of botulinum toxin injection and lateral internal sphincterotomy for the treatment of chronic anal fissure. Dis Colon Rectum. 2003;46: IX. ENDNOTES a. Hyperhidrosis Disease Severity Scale The HDSS is a 4-point scale designed to assess the severity of hyperhidrosis in everyday clinical practice or in clinical research and the effectiveness of treatment. The HDSS can be administered by an interviewer or self-completed by the patient. The HDSS assess disease severity based on the extent of sweating-related impairment of daily activities. Question Score My (underarm) sweating is never noticeable and never interferes 1

13 with my daily activities My (underarm) sweating is tolerable but sometimes interferes with my daily activities My (underarm) sweating is barely tolerable and frequently interferes with my daily activities. My (underarm) sweating is intolerable and always interferes with my daily activities b. This recommendation is based on the results of a 6-month study in which botulinum toxin A was administered at 3-month intervals. These injections seemed to have a cumulative effect with subsequent injections. 10 A longer study of 9-months duration demonstrated the benefit of Botox injections (three injections separated by 90 days) for the prophylactic treatment of chronic daily headache in patients who were not taking other prophylactic medications. 11 c. Symptoms of achalasia recur in more than 50% of patients within 6 months of treatment with botulinum toxin A. 12 This Prior Authorization Guideline represents the recommendation of Prescription Solutions Pharmacy and Therapeutics (P&T) Committee. It is based upon the P&T Committee s review of the available evidence as of the date of drafting or revision of this Prior Authorization Guideline. It is subject to updating from time to time, based upon changes in scientific knowledge and information. This Prior Authorization Guideline is intended as a resource for making coverage decisions for Health Plan members, but it does not replace an individualized case-by-case review and medical necessity determination for each Health Plan member. Copyright 2006 by Prescription Solutions. All rights reserved. This Prior Authorization Guideline is intended for use by Prescription Solutions and Health Plan employees and applicable contracted providers and practitioners only. The information contained in this Prior Authorization Guideline is confidential and proprietary to Prescription Solutions and shall not be used, reproduced, or transferred in whole or in part without Prescription Solutions prior written consent.