BlueCross BlueShield of Tennessee Medical Policy Manual

OnabotulinumtoxinA (Botox®)

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

POLICY

INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications

• Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication

• Treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis) in adults or pediatric patients 5 years of age or older who have an inadequate response to or are intolerant of an anticholinergic medication

• Prophylaxis of headaches in adult patients with chronic migraine (≥15 days per month with headache lasting 4 hours a day or longer)

• Treatment of spasticity in patients 2 years of age and older

• Treatment of cervical dystonia in adults, to reduce the severity of abnormal head position and neck pain associated with cervical dystonia

• Treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents. Safety and effectiveness have not been established in patients under age 18.

• Treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and older

Compendial Uses

• Achalasia
• Chronic anal fissures
• Essential tremor
• Excessive salivation (ptyalism)
• Hemifacial spasm
• Spasmodic dysphonia (laryngeal dystonia)
• Oromandibular dystonia
• Myofascial pain syndrome
• Focal hand dystonia
• Facial myokymia
• Hirschsprung disease with internal sphincter achalasia
• Orofacial tardive dyskinesia
• Painful bruxism
• Palatal myoclonus
• First bite syndrome
• Palmar or gustatory (Frey’s syndrome) hyperhidrosis

All other indications are considered experimental/investigational and not medically necessary.

EXCLUSIONS

Coverage will not be provided for cosmetic use.

COVERAGE CRITERIA

Blepharospasm

Authorization of 12 months may be granted for treatment of blepharospasm when all of the following are met:

• Member is 12 years of age or older
• Member is diagnosed with blepharospasm including blepharospasm associated with dystonia, benign essential blepharospasm or VII nerve disorder.

Cervical Dystonia

Authorization of 12 months may be granted for the treatment of adults with cervical dystonia (e.g., torticollis) when all of the following are met: 

• There is abnormal placement of the head with limited range of motion in the neck
• Member is 18 year of age and older.

Chronic Migraine Prophylaxis

Authorization of 6 months (two injection cycles) may be granted for treatment of chronic migraine prophylaxis when all of the following criteria are met:

• Member experiences headaches 15 days or more per month.
• Member experiences headaches lasting 4 hours or longer on at least 8 days per month.
• Member completed an adequate trial of (or has a contraindication to) two migraine preventative therapies coming from at least 2 of the following classes with a trial of each medication at least 60 days in duration:

• Antidepressants (e.g., amitriptyline, venlafaxine)
• Antiepileptic drugs (AEDs) (e.g., divalproex sodium, topiramate, valproate sodium)
• Beta-adrenergic blocking agents (e.g., metoprolol, propranolol, timolol, atenolol, nadolol)
• Calcitonin gene-related peptide (CGRP)-targeting therapies (e.g., fremanezumab, galcanezumab, epitinezumab, rimegepant, atogepant).

• Member has signs and symptoms consistent with chronic migraine diagnostic criteria as defined by the International Headache Society (IHS).

• Member is 18 years of age or older

Overactive Bladder with Urinary Incontinence

Authorization of 12 months may be granted for treatment of overactive bladder with urinary incontinence, urgency, and frequency when all of the following criteria are met:

• The member has tried and failed behavioral therapy.

• The member has had an inadequate response or experienced intolerance to two agents from either of the following classes:

• Anticholinergic medication (e.g., Vesicare [solifenacin], Enablex [darifenacin], Toviaz [fesoterodine], Detrol/Detrol LA [tolterodine], Sanctura/Sanctura XR [trospium], Ditropan XL [oxybutynin]).

• Beta-3 adrenergic agonist (e.g., Myrbetriq [mirabegron], Gemtesa [vibegron]).

• Member is 18 years of age or older.

Primary Axillary, Palmar, and Gustatory (Frey’s Syndrome) Hyperhidrosis

Authorization of 12 months may be granted for treatment of primary axillary, palmar, or gustatory (Frey’s syndrome) hyperhidrosis when all of the following criteria are met:

• Significant disruption of professional and/or social life has occurred because of excessive sweating.
• Topical aluminum chloride or other extra-strength antiperspirants are ineffective or result in a severe rash.
• Member is 18 years of age or older.

Strabismus

Authorization of 12 months may be granted for treatment of strabismus when all of the following criteria are met:

• Strabismus interference with normal visual system development is likely to occur and spontaneous recovery is unlikely.
• Member is 12 years of age or older.
• Note: Strabismus repair is considered cosmetic in adults with uncorrected congenital strabismus and no binocular fusion.

Upper or Lower Limb Spasticity

Authorization of 12 months may be granted for treatment of upper or lower limb spasticity when all of the following are met

• Member is 2 years of age or older
• Member has a primary diagnosis of upper or lower limb spasticity or as a symptom of a condition causing limb spasticity (including focal spasticity or equinus gait due to cerebral palsy).

Urinary Incontinence  Due to Detrusor Overactivity Associated with a Neurologic Condition (e.g., Spinal Cord Injury, Multiple Sclerosis)

Authorization of 12 months may be granted for treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis) when all of the following criteria are met:

• The member has tried and failed behavioral therapy
• The member has had an inadequate response or experienced intolerance to one agent from either of the following classes:

• Anticholinergic medication (e.g., Vesicare [solifenacin], Enablex [darifenacin], Toviaz [fesoterodine], Detrol/Detrol LA [tolterodine], Sanctura/Sanctura XR [trospium], Ditropan XL [oxybutynin]).

• Beta-3 adrenergic agonist (e.g., Myrbetriq [mirabegron] 

• Member is 5 years of age or older.

Achalasia

Authorization of 12 months may be granted for treatment of achalasia when the member has tried and failed or is a poor candidate for conventional therapy such as pneumatic dilation and surgical myotomy.

Chronic Anal Fissures

Authorization of 12 months may be granted for treatment of chronic anal fissures when the member has not responded to first line therapy such as topical calcium channel blockers or topical nitrates.

Essential Tremor

Authorization of 12 months may be granted for treatment of essential tremor.

Excessive Salivation

Authorization of 12 months may be granted for treatment of excessive salivation (chronic sialorrhea or ptyalism) when the member has been refractory to pharmacotherapy (e.g., anticholinergics).

Hemifacial Spasm

Authorization of 12 months may be granted for treatment of hemifacial spasm.

Spasmodic Dysphonia (laryngeal dystonia)

Authorization of 12 months may be granted for treatment of spasmodic dysphonia (laryngeal dystonia).

Oromandibular Dystonia

Authorization of 12 months may be granted for treatment of oromandibular dystonia.

Myofascial Pain Syndrome

Authorization of 12 months may be granted for treatment of myofascial pain syndrome when the member has tried and failed all of the following:

• Physical therapy
• Injection of local anesthetics into trigger points
• Injection of corticosteroids into trigger points

Focal Hand Dystonia

Authorization of 12 months may be granted for the treatment of focal hand dystonias.

Facial Myokymia

Authorization of 12 months may be granted for the treatment of facial myokymia.

Hirschsprung Disease with Internal Sphincter Achalasia

Authorization of 12 months may be granted for the treatment of Hirschsprung’s disease with internal sphincter achalasia following endorectal pull through and the member is refractory to laxative therapy.

Orofacial Tardive Dyskinesia

Authorization of 12 months may be granted for the treatment of orofacial tardive dyskinesia when conventional therapies have been tried and failed (e.g., benzodiazepines, clozapine, or tetrabenazine).

Painful Bruxism

Authorization of 12 months may be granted for the treatment of painful bruxism when the member has had an inadequate response to a night guard and has had an inadequate response to pharmacologic therapy such as diazepam.

Palatal Myoclonus

Authorization of 12 months may be granted for the treatment of palatal myoclonus when the member has disabling symptoms (e.g., intrusive clicking tinnitus) who had an inadequate response to clonazepam, lamotrigine, carbamazepine or valproate.

First Bite Syndrome

Authorization of 12 months may be granted for the treatment of first bite syndrome when the member has failed relief from analgesics, antidepressants or anticonvulsants.

CONTINUATION OF THERAPY  

• All members (including new members) requesting authorization for continuation of therapy for approvable conditions other than migraine prophylaxis must meet all requirements in coverage criteria and be experiencing benefit from therapy.

• Authorization of 12 months may be granted for treatment of chronic migraine prophylaxis when the member has achieved or maintained a reduction in monthly headache frequency since starting therapy with Botox.

DOSAGE AND ADMINISTRATION

Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines.

Adults: Dosing should not exceed a cumulative dose of 400 units every 84 days

Pediatric (patients less than 18 years of age): Dosing should not exceed the lessor of 10 units/kg or 340 units every 84 days.

MEDICATION QUANTITY LIMITS

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

1. Botox [package insert]. Madison, NJ: Allergan USA, Inc; November 2023.
2. DRUGDEX® System (electronic version). Truven Health Analytics, Ann Arbor, MI. Available at http://www.micromedexsolutions.com. Accessed July 10, 2024.
3. AHFS Drug Information. http://online.lexi.com/lco. Accessed July 10, 2024.
4. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-45.
5. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137(10):840-849. 
6. Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009;16(9):968-981.
7. Pringsheim T, Davenport W, Mackie G, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2):S1-59.
8. Zesiewics TA, Elble RJ, Louis ED et al. Evidence-based guideline update: Treatment of essential tremor: Report of the Quality Standards Subcommittee of the American Academy of Neurology: Neurology 2011; 77: 1752-1755.
9. Restivo D, Panebianco M, Casabona A et al.  Botulinum Toxin A for Sialorrhea Associated with Neurological Disorders: Evaluation of the Relationship between Effect of Treatment and the Number of Glands Treated. Toxins 2018;55:1-10.
10. Lakraj AA, Moghimi N, Jabbari B. Sialorrhea: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins. Toxins 2013, 5, 1010-1031
11. Zoons E, Dijkgraaf M, Dijk J et al.  Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.  J Neurol 2012;259: 2519-2526.
12. Conrin L, Karp BI, Alter K et al. Long Term Follow-up Botulinum Toxin Therapy for Focal Hand Dystonia: Outcome at 10 or More Years: Mov Disord. 2011 Mar; 26(4): 750–753.
13. Daele D, Finnegan E, Rodnitzky R et al.  Head and Neck Muscle Spasm After Radiotherapy.  Otolaryngol Head and Neck Surg 2002;128:956-959.
14. Han-Guerts I, Hendrix V, Blaauw I et al.  Outcome after Anal Intrasphincteric Botox Injection in Children with Surgically Treated Hirschsprung Disease. JPGN 2014; 59: 604-607.
15. Asutay F, Atalay Y, Asutay H, Huseyin Acar A.  The Evaluation of the clinical effects of Botulinum Toxin on Nocturnal Bruxism.  Pain Research and Management 2017;1-5.
16. Gosain A, Frykman PK, Cowles RA, et al. Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis. Pediatr Surg Int. 2017; 33(5):517–521.
17. Thuruthiath N, Arayamparambil R.   Essential palatal myoclonus: A rare cause of objective tinnitus.  J Adv Med Heath Res 2016;3:1-3.
18. Laccourreye O, Werner A, Garcia D, Malinvaud D, Tran Ba Huy P, Bonfils P.  First bite syndrome.  Euro Ann Otolaryngol Head Neck Diseases. 2013; 130:269-273.
19. Linkov G et al. First bite syndrome: incidence, risk factors, treatment, and outcomes. The Laryngoscope. 2012; 122: 1773-1778.
20. Slotema CW;van Harten PN;Bruggeman R;Hoek HW. Botulinum toxin in the treatment of orofacial tardive dyskinesia: a single blind study.  Prog Neuropsychopharmacol Biol Psychiatry 2008;32(2):507-509.
21. Odderson IR. Hyperhidrosis treated by botulinum A exotoxin. Dermatol Surg. 1998;24(11):1237-1241.
22. Solomon BA, Hayman R. Botulinum toxin type A therapy for palmar and digital hyperhidrosis. J Am Acad Dermatol. 2000;42(6):1026-1029.
23. 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.
24. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders: 3rd edition. Cephalalgia. 2018;Vol. 38(1) 1–211.
25. Glader L, Delsing C, Hughes A et al. Sialorrhea in cerebral palsy. American Academy for Cerebral Palsy and Developmental Medicine Care Pathways. https://www.aacpdm.org/publications/care-pathways/sialorrhea. Accessed August 3, 2021.
26. Garuti G, Rao F, Ribuffo V et al. Sialorrhea in patients with ALS: current treatment options. Degener Neurol Neuromuscul Dis. 2019; 9: 19–26.
27. Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A; American Headache Society. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache. Published online March 11, 2024.
28. Cameron AP, Chung DE, Dielubanza EJ, et al. The AUA/SUFU Guideline on the Diagnosis and Treatment of Idiopathic Overactive Bladder. J Urol. 2024;212(1):11-20.
29. Smith C, Pariser D. Primary Focal Hyperhidrosis. Waltham, MA. UpToDate. Last Modified May 13, 2024. https://www.uptodate.com/contents/primary-focal-hyperhidrosis. Accessed July 22, 2024.

ORIGINAL EFFECTIVE DATE: 12/98

MOST RECENT REVIEW DATE: 4/2/2025

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information