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Home , Botulinum toxin

Clinical Policy: Neuromuscular Blocking Agents- Reference Number: CP.CPA.250 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Medicaid – Medi-Cal Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description The following are neuromuscular blocking agents requiring prior authorization: onabotulinuumtoxin A (Botox®), abobotulinumtoxin A (Dysport®), incobotulinumtoxin A (Xeomin®), rimabotulinum type-B (Myobloc®).

FDA approved indication Botox is indicated: • For the treatment of in patients 12 years and older • For the treatment of associated with in patients 12 years and older • For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia • For the treatment of severe primary axillary that is inadequately managed by topical agents in adult patients • For the treatment of upper limb in adult patients • To prevent in adult patients with chronic (15 or more days per month with lasting 4 hours a day or longer) • For the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition [e.g., spinal cord injury (SCI), multiple sclerosis (MS)] in adults who have an inadequate response to or are intolerant of an medication • For the treatment of (OAB) with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication

Dysport is indicated: • For the treatment of adults with cervical dystonia • For the treatment of the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adult patients <65 years of age • For the treatment of spasticity in adult patients • For the treatment of lower limb spasticity in pediatric patients 2 years of age and older

Xeomin is indicated:

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• For the treatment of adults with cervical dystonia, to decrease the severity of abnormal head position and neck pain in both -naïve and previously treated patients • For the treatment of Blepharospasm in adults previously treated with onabotulinumtoxinA (Botox) • For the treatment of temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients • For the treatment of upper limb spasticity in adult patients

Myobloc is indicated: • For the treatment of adults with cervical dystonia (CD) to reduce the severity of abnormal head position and neck pain associated with CD.

Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria

It is the policy of health plans affiliated with Centene Corporation® that Botox, Dysport, Xeomin and Myobloc are medically necessary when the following criteria are met:

I. Initial Approval Criteria A. All Indications (must meet all): 1. All requests require the following: a. Condition for which the toxin will be used; b. Anticipated frequency of injection; c. Total dose per visit; d. Previous therapies tried; 2. Confirmed diagnosis of one of the following: a. Strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age or older; b. Hemifacial ; c. spasm; d. Jaw-closing oromandibular dystonia; e. (laryngeal dystonia, lingual dystonia, laryngeal spasm); f. (cervical dystonia); g. Focal task-specific dystonia; h. Head and neck ; i. Dynamic muscle contractions in pediatric ; j. Limb spasticity; k. Frey’s Syndrome (gustatory sweating) secondary to parotid surgery; l. Sialorrhea in Parkinson’s ; m. Detrussor sphincter (lower urinary tract dysfunction); n. Overactive bladder or urinary incontinence due to detrusor overactivity associated with a neurologic condition;

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o. Focal hand (organic writer’s cramp) when incapacitating and refractive to medical treatment including oral medications; p. Symptomatic patients with primary, idiopathic ; q. Focal, primary axillary or palmar hyperhidrosis; r. Chronic ; s. Internal anal sphincter (IAS) achalasia; t. Chronic migraine headache; 3. For overactive bladder or urinary incontinence, failure or clinically significant adverse effects to at least two anticholinergic agents (e.g., oxybutynin immediate and extended release tabs, Oxytrol patch, Gelnique gel,, tolteridine immediate and extended release, Toviaz, Enablex, Vesicare, trospium immediate and extended release); 4. For focal hand dystonias (organic writer’s cramp) both of the following (a and b): a. Documentation of functional limitations; b. Failure or clinically significant adverse effects to oral medications (, beta-blockers and ); 5. For primary, idiopathic esophageal achalasia, one of the following (a, b, c, d, or e): a. Failure to conventional therapy (e.g., nitrates or calcium channel blockers) unless contraindicated or clinically significant adverse effects are experienced; b. Member is ineligible for surgical treatment due to advance age or multiple co- morbidities (poor surgical risk); c. Member is at high risk of complications of pneumatic dilation or surgical myotomy; d. Failure of prior myotomy or dilation; e. Member has an epiphrenic diverticulum or hiatal hernia, both of which increase the risk of dilation-induced perforation; 6. For axillary or palmar hyperhidrosis both of the following (a and b): a. Failure to topical antiperspirants (e.g., Drysol) unless contraindicated or clinically significant adverse effects are experienced; b. Condition creates a significant disruption to patient’s daily life and ability to work/function or patient has recurrent or chronic irritations and/or infections, dermatitis, skin macerations; 7. For chronic anal fissure, failure to topical nitroglycerin or a topical calcium channel blocker unless contraindicated or clinically significant adverse effects are experienced; 8. For internal anal sphincter (IAS) achalasia both of the following (a and b): a. Member has not responded to treatment with laxatives; b. Member has not responded to or is not a candidate for anal sphincter myectomy; 9. For chronic migraine headache, all of the following: a. Persistent history of chronic, debilitating migraine headaches with frequent attacks on 15 or more days per month for longer than 3 months; b. A neurologist has thoroughly evaluated the patient and has established a diagnosis of chronic migraine headaches; c. Documentation of significant functional disability (e.g., work absenteeism, multiple emergency department visits);

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d. Failure to abortive treatment with at least three (3) different therapy classes listed below in Appendix B, unless contraindicated or clinically significant adverse effects to all; e. Failure to prophylactic therapy from at least two (2) different therapy classes listed below in Appendix B, unless contraindicated or clinically significant adverse effects to all. Approval duration: Length of Benefit

B. Other diagnoses/indications 1. Refer to CP.PMN.53 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized)

II. Continued Therapy A. All Indications (must meet all): 1. Currently receiving medication via a health plan affiliated with Centene Corporation or member has previously met initial approval criteria; 2. Documentation of positive response to therapy. Approval duration: Length of Benefit

B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Centene Corporation and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.PMN.53 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized)

III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy – CP.PMN.53 or evidence of coverage documents; B. Cosmetic treatment of hyperfunctional of the upper face including glabellar frown lines, deep forehead wrinkles and periorbital wrinkles (crow’s feet).

IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key N/A

Appendix B: General Information Medications for Abortive Class Commonly Used Examples Dose Limit/ Maximum Dose Triptans* Imitrex (sumitriptan), Maxalt (rizatriptan), Varies according to Zomig (zolmitriptan), Amerge (naratriptan), the agent used Axert (almotriptan), Frova (frovatriptan), Relpax (eletriptan)

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Class Commonly Used Examples Dose Limit/ Maximum Dose Ergot derivatives Cafergot (/), D.H.E.-45 Varies according to (dihydroergotamine) the agent used Analgesics* aspirin, acetaminophen, (morphine, Varies according to oxycodone), combinations (APAP/codeine, the agent used APAP hydrocodone) Non-steroidal Motrin (ibuprofen), Naprosyn (naproxen), Varies according to anti- Relafen (nabumetone), Voltaren (diclofenac), the agent used inflammatory Orudis (ketoprofen), Clinoril (sulindac), agents (NSAIDs) Toradol (ketorolac) Combination Midrin (isometheptene/APAP), Fiorinal Varies according to products (butalbital/aspirin), Fioricet (butalbital/APAP) the agent used

Medications for Prophylaxis Migraine Treatment Class Commonly Used Examples Dose Limit/ Maximum Dose Anticonvulsants* divalproex (Depakote®), topiramate (Topamax®) Varies according to the agent used Beta blockers propranolol (Inderal®), metoprolol (Lopressor®), Varies according to atenolol (Tenormin®) the agent used Antidepressants/ (Elavil®), venlafaxine (Effexor®) Varies according to Tricyclic the agent used antidepressants Non steroidal Fenoprofen (Nalfon®), ibuprofen (Motrin®), Varies according to anti- ketoprofen (Orudis®), naproxen (Naprosyn®) the agent used inflammatory drugs (NSAIDs) * Check the member’s benefits; some agents may require prior authorization. • All botulinum toxin products have a black box warning which cautions patients that the effects of the drug may spread from the area of injection and cause symptoms similar to , including potentially life-threatening swallowing and breathing difficulty. • The potency Units of botulinum toxin products are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of one product cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method. • Safety and effectiveness have not been established for the prophylaxis of episodic migraine (14 headache days or fewer per month) and is a Class 2b recommendation in Micromedex • Safety and effectiveness have not been established for the treatment of all headache types except migraine as outlined above. • For detrusor overactivity associated with a neurologic condition there was no additional benefit of Botox 300 Units over 200 Units.

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• Safety and effectiveness have not been uniformly established for the treatment of temporomandibular disorders (TMD). Use of botulinumtoxin for this indication is a Class IIb recommendation in Micromedex based on a single study from 1999. A review of two clinical studies (from 2002 and 2011) (15 and 21 patients) found no significant differences in pain reduction between botulinumtoxin and placebo. Other small studies (from 2005 - Italy and 2008 - Turkey) have been performed and showed improvement in objective measures of pain (20 patients and 26 patients). The most common total dose of BTX-A used in the studies was 25u for each temporalis muscle and 50u for each masseter muscle. The studies did not repeat the dosing, but measured efficacy at 16 weeks post dose. The 2003 Guidelines for diagnosis and management of disorders involving the temporomandibular joint and related musculoskeletal structures mention Botox as a possible treatment option for TMJ based on its mechanism of action and the pathophysiology of TMD. • TMD “gold standard” treatment continues to be: 1) TMJ intraoral orthotic; 2) Muscle relaxants by mouth; and 3) Home muscle relaxation exercises/techniques. • Myobloc appears to be effective in the treatment of cervical dystonia in patients who have developed tolerance to or who are not responsive to botulinum toxin type A (Botox). Experience with Myobloc in patients who have not previously received Botox is limited. There is limited data supporting the use of Myobloc in blepharospasm, spasmodic dysphonia, axillary hyperhidrosis, plantar/palmar hyperhidrosis, gustatory sweating, sialorrhea, upper-limb spasticity due to , anal fissure, detrusor hyperreflexia due to multiple sclerosis and myofascial pain syndrome. • Limb spasticity may be caused by Heredity spastic paraplegia; multiple sclerosis or other demyelinating of the central nervous system; ; infantile cerebral palsy; Stroke.

Appendix C: Therapeutic Alternatives – N/A V. Dosage and Administration Drug Name Indication Dosing Regimen Maximum Dose Onabotulinuumtoxin See dosing chart See dosing chart below Varies A (Botox) below Abobotulinumtoxin Cervical dystonia Initial dose is 500 units IM as Varies A (Dysport) a divided dose among the affected muscles. Re- treatment every 12 to 16 weeks or longer, as necessary, based on return of clinical symptoms.

Abobotulinumtoxin Upper Limb As clinically appropriate Varies A (Dysport) Spasticity Abobotulinumtoxin Pediatric Lower 10 to 15 units/kg total per Total dose per A (Dysport) Limb Spasticity treatment session. treatment: 15 units/kg for unilateral lower limb injections,

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30 units/kg for bilateral injections, or 1000 units, whichever is lower. Incobotulinumtoxin Cervical dystonia The usual starting dose is 120 Varies A (Xeomin) units per treatment session, doses up to 300 units may be used in treatment-experienced patients. Dose, number, and location of injection sites should be based on the number and location of muscles involved, severity of dystonia, and response to any previous botulinum toxin injections. Incobotulinumtoxin Blepharospasm When initiating Xeomin Varies A (Xeomin) therapy, the dose, number, and location of injections should be based on the previous dosing of Botox. If the previous dose of Botox is not known, the recommended starting dose is 1.25-2.5 units per injection site. Incobotulinumtoxin Upper limb Dosing varies based on maximum A (Xeomin) spasticity location of muscles to be cumulative dose treated (refer to dosing chart is 400 units in the prescribing information). Rimabotulinum Cervical dystonia The initial dose of Myobloc Varies toxin type-B for patients with a history of (Myobloc) tolerating botulinum toxin injections is 2500 to 5000 U divided among affected muscles. Give patients without a history of tolerating botulinum toxin injections a lower initial dose.

Optimize subsequent dosing according to the patient's individual response. The duration of effect has been

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observed in studies to be between 12 and 16 weeks at doses of 5000 U or 10,000 U. Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic.

Botox (onabotulinumtoxin A) Dose Chart Condition Average Duration of Effect Average Dose Blepharospasm 12.5 weeks 5 units per site Strabismus 6-8 weeks to 6-12 months 2.5 to 5 units per muscle (max 25 units) Cervical dystonia 4 weeks to 3 months 200 to 300 units divided among affected muscles Oromandibular dystonia* 10 to 14 weeks 25 to 50 units per masseter muscle, 5 to 40 units per temporalis Spasmodic dysphonia* 3-6 months 0.031 to 10 units per vocal cord. 5 to 30 units in abductor muscle Overactive bladder 12 weeks Total dose 100 Units, as 0.5 mL (5 Units) injections across 20 sites into the detrusor. Repeat doses should be 12 weeks apart Spastic muscle contracture of 1-6 months 3 to 6 units/kg (maximum 12 pediatric cerebral palsy* units/kg). total dose 82 to 220 units divided among affected muscles Childhood 4-8 months 8 to 80 units/kg following failure of Baclofen, benzodiazepines, and antiseizure medications* Chronic anal fissure* Single Injection 20 units both sides Internal anal sphincter Single treatment. Patient may 15 units to 25 units in each achalasia* require repeat treatment. quadrant or up to 50 units on Adults or children either side of IAS Gustatory sweating (Frey's 6 months 15 to 75 units per injection syndrome) * Axillary Hyperhidrosis 4-12 months 50 units per axilla Plantar/palmar hyperhidrosis* 4-12 months 100 to 165 units per palm 3-4 months 155 total units given in 5 to 40 units/site Neurogenic bladder 8-12 months 200 units given in multiple sites Upper Limb Spasticity 12 weeks 12.5 Units-50 Units in one site

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*Unlabeled uses

VI. Product Availability Drug Availability Onabotulinumtoxin A (Botox) Powder for injection (lyophilized) 100 units, or 200 units of botulinum toxin type A per vial

Abobotulinumtoxin A (Dysport) Powder for injection 500 unit vial; powder for injection 300 unit vial Incobotulinumtoxin A (Xeomin) Lyophilized powder for injection 50 units, 100 units, or 200 units Rimabotulinum toxin type-B 2,500, 5,000 and 10,000 units of rimabotulinum toxin (Myobloc) type B per vial

VII. References 1. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 3, 2016. 2. Maria G, Cassetta E, Gui D, et al., A Comparison of botulinum toxin and saline for the treatment of chronic anal fissure. N Engl J Med. 1998; 338(4): 217-220. 3. Mosby-Year Book, Inc., Mosby’s GenRx: The Complete Reference for Generic and Brand Drugs, 8th Ed. St. Louis, MO: Mosby, 1999. 4. American Hospital Formulary Service Drug Information. AHFS Web site. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 3, 2016. 5. Biglan AW, et al. with botulinum A toxin. Ophthalmology 1989;96(7): 935-943. 6. Biglan AW, et al., Management of facial spasm with toxin type A (Oculinum). Arch Otolaryngol Head Neck Surg. 1998; 114(12): 1407-1412. 7. Kalra HK, et al., Side effects of the use of botulinum toxin for treatment of benign essential blepharospasm and . Ophthalmic Surg. 1990;21(5): 335-338. 8. Brisinda et al., A comparison of injections of botulinum toxin and topical hitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 1999; 341: 65-69. 9. Schulte-Mattler WJ, Wieser T, Zierez S. Treatment of tension-type headache with botulinum toxin: a pilot study. Eur J Med Res. 1999; 4(5): 183-186. 10. Wheeler A.H., Botulinum toxin A. adjunctive therapy for refractory headaches associated with pericranical muscle tension. Headache. 1998;38(6):468-471. 11. Domzal TM. Botulinum toxin in the treatment of pain. Neurol Neurochir Pol. 1998;32 Suppl 1:57-60. 12. Hobson DE, Gladish DF. Botulinum toxin injection for cervicogenic headache. Headache. 1997:37(4):253-255. 13. Zwart JA, Bovim G, Sand T, Sjaastad O. : botulinum toxin paralysis of temporal muscles. Headache. 1994; 34 (8): 458-462. 14. Karamfilov T, Konrad H, Karte K, et al., Lower relapse rate of botulinum toxin A therapy for axiallary hyperhidrosis by dose increase. Arch Dermatol. 2000; 136(4): 487-490. 15. Naver H, Swartling C, Aquilonius SM. Palmar and axillary hyperhidrosis treated with botulinum toxin: one-year clinical follow-up. Eur J Neurol. 2000; 7(1): 55-62.

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16. Heckmann M, Breit S, Ceballos-Baumann A, et al., Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis. J Am Acad Dermatol. 1999; 41(6): 987-990. 17. Odderson IR. Hyperhidrosis treated by botulinum A . Dermatol Surg. 1998; 24(11): 1237-1241. 18. Solomon BA, Hayman R. Botulinum toxin type A therapy for palmar and digital hyperhidrosis. J Am Acad Dermatol. 2000; 42(6):1026-1029. 19. USP DI ® Drug Information for the Health Care Professional. 20th ed. “B” Monographs. Botulinum Toxin Type A (Parenteral-Local); 2000. STAT! Ref (Accessed June 30, 2000). 20. Sedano MJ, Trejo JM, Macarron JL, Polo JM, Berciano J, Calleja J. Continuous facial myokymia in multiple sclerosis: treatment with botulinum toxin. Eur Neurol. 2000; 43(3): 137-40. 21. Boghen Dr. Disorders of facial motor function. Curr Opin Ophthalmol. 1996 Dec;7(6): 48- 52. 22. Lou JS, Pleninger P, Kurlan R. Botulinum toxin A is effective in treating trismus associated with postradiation myokymia and muscle spasm. Mov Disord. 1995 Sep; 10(5): 680-681. 23. Ruusuvaara P, Setala K. Long term treatment of involuntary facial using botulinum toxin. Acta Ophthalmol (Copenh). 1990 Jun; 68(3): 331-8. 24. Jordan DR, Anderson RL, Thiese SM. Intractable orbicularis myokymia: treatment alternatives. Ophthalmic Surg. 1989; 20(4): 280-283. 25. Freund B, Schwartz M, Symington JM. Botulinum toxin: new treatment for temporomandibular disorders. Br J Oral Maxillofac Surg. 2000; 38(5): 466-471. 26. Freund B, Schwartz M, Symington JM. The use of botulinum toxin for the treatmetn of temporomandibular disorders: preliminary findings. J Oral Maxillofac Surg. 1999; 57(8): 916-921. 27. Freund B, Schwartz M. The use of botulinum toxin for the treatment of temporomandibular disorder. Oral Health. 1998; 88(2):32-37. 28. Moore AP, Wood GD. Medical treatment of recurrent temporomandibular joint dislocation using botulinum toxin A., Br Dent J. 1997; 183(11-12): 415-417. 29. Daelen B, Thorwirth V, Koch A. Treatment of recurrent dislocation of the temporomandibular joint with type A botulinum toxin. Int J Oral Maxillofac Surg. 1997; 26(6): 458-460. 30. Lew MF, Brashear A, Factor S. The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: summary of three controlled clinical trials. Neurology. 2000;55(12 Suppl 5): S29-35. 31. Munchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ. 2000;320:161-165. 32. Brashear A, Lew MF, Dykstra DD, et al., Safety and efficacy of NeuroBloc (botolinum toxin type B) in type A-responsive cervical dystonia. Neurology. 1999; 53(7): 1439-1446. 33. Brin MF, Lew MF, Adler CH, et al., Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999; 53(7): 1431-1438. 34. Cullis PA, O’Brien CF, Truong DD, et al., Botulinum toxin type B: an open-label, dose- escalation, safety and preliminary efficacy study in cervical dystonia patients. Adv Neurol. 1998;78: 227-230. 35. Pasricha PJ, Ravich WJ, Henrix TR, et al., Intraspincteric botulinum toxin for the treatment of achalasia. N Engl J Med 1995;322: 774-78.

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36. Pasricha PJ, Rai R, Ravich WJ, et al., Botulinum toxin for achalasia: Long term outcome and predictors of response. Gastroenterol 1996; 110: 1410-1415. 37. Vaezi MF, Richter JE, Wilcox M, et al., Botulinum toxin versus pneumatic dilation in the treatment of achalasia: A randomized trial. Gut 1999, 44: 231-239. 38. Prakash C, Freedland KE, Chan MF, et al., Botulinum toxin injections for achalasia symptoms can approximate the short-term efficacy of a single pneumatic dilation: A survival analysis approach. Am J Gastroenterol 1999; 94: 328-333. 39. Gordon JMI, Eager ELY. Prospective study of esophageal botulinum toxin in high-risk achalasia patients. Am J Gastroenterol; 1997; 92: 1812-1817. 40. Richter MF. American College of Gastroenterology Practice. Diagnosis and Management of Achalasia. Practice Guidelines. Am J of Gastroenterol 1999; 94(12): 3406-3412. 41. Kolbasnik J, Waterfall WE, Fachnie B, Chen Y, et al., Long term efficacy of botulinum toxin in classical achalasia: a prospective study. Am J Gastroenterol 1999; 94(12): 3434- 39. 42. Muehldorfer SM, Schneider TH, et al., Esophageal achalasia: intrasphincteric injection of botulinum toxin, A versus balloon dilation. Endoscopy 1999; 31(7): 231-34. 43. Dysport [Prescribing Information] Wrexham, UK, Ipsen Biopharm Ltd.; July 2015. 44. Botox [Prescribing Information] Irvine, CA , Allergan; January 2016. 45. Myobloc [package insert] South San Francisco, CA; Solstice Neurosciences: June 2012. 46. Mathew NT et al. A double-blind comparison of onabotulinumtoxin A (Botox) and topiramate (Topamax) for the prophylactic treatment of chronic migraine: A pilot study. Headache November 2009 49:1466-1478. 47. Blumenfeld AM et al. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache February 2008 48:210-220. 48. Petri S et al. Botulinum toxin as preventative treatment for migraine: A randomized double-blind study. Euro Neurol 2009 62:204-211. 49. Aurora SK et al. Botulinum toxin type A as prophylactic treatment of episodic migraine headache: A randomized, placebo controlled, exploratory trial. Headache April 2007 47:486-499. 50. Xeomin [Prescribing Information] Franksville, WI. Merz Pharmaceuticals; December 2015. 51. American Society of Temporomandibular Joint Surgeons. Guidelines for diagnosis and management of disorders involving the temporomandibular joint and related musculoskeletal structures. Accessed June 3, 2016 at http://astmjs.org/guidelines.html 52. Hoque A, McAndrew M. Use of Botulinum Toxin in Dentistry. NY State Dent J, 2009; 75(6):52-5. 53. Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain, 2002; 99:465-73. 54. Ernberg M, Hedenberg-Magnusson B, List T, Svensson P. Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study. Pain, 2011; 152:1988-96. 55. Guarda-Nardini L, Manfredini D, Salamone M, et al. TMD Clinic, Cranio. 2008 Apr;26(2):126-35. 56. Karacalar A, Yilmaz N, Bilgici A, Bas B, Akan H. Botulinum toxin for the treatment of temporomandibular joint disk disfigurement: clinical experience. J Craniofac Surg. 2005 May;16(3):476-81.

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57. Friedmacher F and Puri P. Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis. Pediatr Surg Int. Aug 2012 28;8: 765-771. 58. Doodnath R and Puri P. Long-term outcome of internal sphincter myectomy in patients with internal anal sphincter achalasia. Pediatr Surg Int October 2009 25;10: 869-871. 59. Estemalik E and Tepper S. Preventive treatment in migraine and the new US guidelines. Neuropsychiatric Disease and Treatment 2013;9:709-20. 60. Silberstein SD, Holland S, Freitag F et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Neurology 2012;78:1337-45. 61. Perry WB, Dykes SL, Buie WD et al. Practice parameters for the management of anal fissures (3rd revision). Dis Colon Rectum 2010;53:1110-15. 62. Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of complexing for treatment of cervical dystonia. Neurology. 2005;64(11):1949-1951. 63. Fernandez HH, Pagan F, Danisi F, Greeley D, Jankovic J, Verma A, Sethi K, Pappert EJ; XCiDaBLE Study Group. Prospective Study Evaluating IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm: Interim Results from the First 145 subjects with Cervical Dystonia. Tremor and Other Hyperkinet Mov. 2013;17(3). pii:tre-03-139-2924-1. Print 2013. 64. Dressler D. Routine use of Xeomin in patients previously treated with Botox: long term results. Eur J Neurol. Dec 2009;16 Suppl 2:2-5.

Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template. Minor changes to verbiage 07.12.17 11.17 and grammar. References updated.

Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of

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insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. ©2017 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene® and Centene Corporation® are registered trademarks exclusively owned by Centene Corporation.

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