Botulinum Toxin
DESCRIPTION
Botulinum toxin, produced by the bacterium Clostridium botulinum, is one of the most potent naturally occurring neurotoxins known. It induces chemodenervation by binding to acceptors on motor nerve terminals, entering the terminals and blocking the release of acetylcholine and other neurotransmitters at the neuromuscular junction. This renders smooth and striated muscles incapable of contraction. Additionally, as sympathetic innervation of the sweat glands is mediated by acetylcholine, botulinum toxin disrupts the cholinergic outflow to the skin and halts glandular secretion.
The minute amount of toxin used clinically produces only partial, localized chemical denervation with transient results. Axons generate temporary sprouts which release acetylcholine and the original nerve terminal is eventually re-established, ending the toxin’s therapeutic activity.
Seven antigenic-specific serotypes of botulinum toxin have been identified, types A, B, C-1, D, E, F and G, but only botulinum toxin types A and B are commercially available. These commercial preparations of the two serotypes (two of serotype A and one of serotype B) vary widely in potency and dosage. They have been given different names to reinforce these differences and to prevent medication errors. It is emphasized that the use of the different formulations of botulinum toxin is not interchangeable.
Examples of preparations of type A botulinum toxin are abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®) and onabotulinumtoxinA (Botox®).
An example of a preparation of type B botulinum toxin is rimabotulintoxinB (Myobloc®).
REFER TO DECISION SUPPORT TREE
POLICY
Botulinum toxin type A (e.g., onabotulinumtoxinA [Botox®], incobotulinumtoxinA [Xeomin®] or abobotulinumtoxinA [Dysport®]) for the treatment of the following conditions is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Strabismus
Severe primary axillary hyperhidrosis
Severe primary palmar hyperhidrosis
Urinary incontinence
Botulinum toxin type A (e.g., onabotulinumtoxinA [Botox) for the prevention of migraine headaches is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Botulinum toxin type A (e.g., onabotulinumtoxinA [Botox®] or abobotulinumtoxinA [Dysport®]) for the treatment of the following is considered medically necessary:
Blepharospasm
Cranial nerve VII disorders (e.g., hemifacial spasms)
Upper limb spasticity
Botulinum toxin types A (onabotulinumtoxinA [Botox®] and abobotulinumtoxinA [Dysport®]) and B (rimabotulintoxinB [Myobloc®]), for the treatment of the following conditions, are considered medically necessary:
Achalasia
Cervical dystonia
Chronic anal fissure
Hereditary spastic paraplegia
Idiopathic torsion dystonia
Infantile cerebral palsy, spastic
Organic writer's cramp
Orofacial dyskinesia
Oromandibular dystonia
Spasmodic dysphonia
Spasmodic torticollis
Spastic hemiplegia
Symptomatic torsion dystonia
Botulinum toxin types A (onabotulinumtoxinA [Botox®] or abobotulinumtoxinA [Dysport®]) and B (rimabotulintoxinB [Myobloc®]), for the treatment of other conditions/diseases, including, but not limited to, the following, are considered investigational:
Anismus
Chronic motor tic disorder; (e.g., de la Tourette syndrome)
Chronic paralytic strabismus except when used with surgical repair to reduce antagonist contracture
Conditions in an individual who is pregnant or nursing
Duane's syndrome with lateral rectus weakness
Gastroparesis
Hirschsprung’s disease
Myofascial pain syndrome
Occipital neuralgia
Prevention of pain associated with breast reconstruction after mastectomy
Restrictive strabismus
Secondary strabismus caused by prior surgical over-recession of the antagonist
Strabismus deviations over 50 prism diopters
Stuttering and/or any other vocal tremors
Temporomandibular joint disease
Treatment of headache or migraine
Treatment of hyperhidrosis adequately managed with topical agents and without associated functional impairment or medical complications
Botulinum toxin types A (onabotulinumtoxinA [Botox®] or abobotulinumtoxinA [Dysport®]) and B (rimabotulintoxinB [Myobloc®]), for the treatment of facial wrinkles, are considered cosmetic.
MEDICAL APPROPRIATENESS
Botulinum toxin A (onabotulinumtoxinA [Botox®] or abobotulinumtoxinA [Dysport®]), for the treatment of ANY ONE of the following conditions, is considered medically appropriate if the following criteria are met:
Strabismus with ALL of the following:
Conditions associated with dystonia
ABSENCE of ALL of the following:
Duane’s syndrome with lateral rectus weakness
Restrictive strabismus
Strabismus secondary to prior surgical over-recession of the antagonist
Strabismus deviations more than 50 prism diopters
Chronic paralytic strabismus except when used with surgical repair to reduce antagonist contracture
Severe primary hyperhidrosis with ALL of the following:
Location is ANY ONE of the following:
Axillary
Palmar
Treatment is not adequately managed with topical agents
The condition causes ANY ONE of the following:
Functional impairment
Medical complications
Urinary incontinence with ALL of the following:
Individual has undergone urodynamic studies with diagnosis of idiopathic detrusor overactivity (IDO)
Anticholinergic therapy has failed to provide adequate control
Botulinum toxin type A (e.g., onabotulinumtoxinA [Botox®]) for the prevention of migraine headaches is considered medically appropriate if the headaches are chronic with ANY ONE the following criteria met:
Initial 6-month trial for migraine headaches with ALL the following:
Occur fifteen days or more per month
Last four hours a day or longer
Experienced for 3 months or more
Symptoms persist despite adequate trials of a minimum of 2 agents from different classes used in the treatment of chronic migraines (e.g., ergot alkaloids, antidepressants, antihypertensives, antiepileptics), unless the individual has contraindications to such medications
Continuation of therapy after 6-month trial for the prevention of migraines with ANY ONE of the following:
Frequency reduced by at least 7 days per month
Duration of headache reduced by at least 100 hours per month
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
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, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
Refer to Dystonia definition located in the Glossary section of this manual.
Use of the four commercially available preparations of botulinum toxin is not interchangeable in potency, dosage or indication. Important safety information concerning the use of these agents is available from the FDA Risk Evaluation and Mitigation Strategy (REMS) program located at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
No controlled studies were found in the published literature that validate the use of botulinum toxin in the treatment/prevention of any other conditions/diseases.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2011). Botulinum toxin (5.01.05). Retrieved June 1, 2011 from BlueWeb.
BlueCross BlueShield Association. Medical Policy Reference Manual. (4:2011). Treatment of hyperhidrosis (8.01.19). Retrieved June 1, 2011 from BlueWeb.
Brubaker, L., Richter, H. E., Visco, A., Mahajan, S., Nygaard, I., Braun, T. M., et al. (2008). Refractory idiopathic urge urinary incontinence and botulinum A injection. The Journal of Urology, 180 (1), 217-222. (Level 1 Evidence)
Lexi-Comp Online. (2011, May). AHFS DI. Botulinum toxin. Retrieved May 31, 2011 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). AbobotulinumtoxinA. Retrieved March 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). OnabotulinumtoxinA. Retrieved March 17, 2010 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). RimabotulinumtoxinB. Retrieved March 17, 2010 from MICROMEDEX Healthcare Series.
Naumann, M, So, Y, Argoff, C. E, Childers, M. K., Dykstra, D. D., Gronseth, G. S., et al,. (2008). Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (An evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70(19), 1707-1714.
U. S. Food and Drug Administration. (2009, July). Center for Drug Evaluation and Research. Myobloc® (RimabotulinumtoxinB) injection. Retrieved March 22, 10 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/103846s5120lbl.pdf.
U. S. Food and Drug Administration. (2010, July). Center for Drug Evaluation and Research. Xeomin (incobotulinumtoxinA) for injection, intramuscular use. Retrieved August 26, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125360lbl.pdf.
U. S. Food and Drug Administration. (2010, March). Center for Drug Evaluation and Research. Botox® (onabotulinumtoxinA). Retrieved March 17, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103000s5189lbl.pdf.
U. S. Food and Drug Administration. (2010, March). Center for Drug Evaluation and Research. Dysport™ for Injection (abobotulinumtoxinA). Retrieved March 18, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125274s0000s0001lbl.pdf.
ORIGINAL EFFECTIVE DATE: 12/1998
MOST RECENT REVIEW DATE: 11/12/2011
ID_BT
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.
Pharmaceutical Decision Support Tree
Botulinum Toxin [abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®), onabotulinumtoxinA (Botox®) and rimabotulintoxinB (Myobloc®)]
Note: Use of the four commercially available preparations of botulinum toxin is not interchangeable in potency, dosage or indication. Important safety information concerning the use of these agents is available from the FDA Risk Evaluation and Mitigation Strategy (REMS) program located at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.
Is the requested medication being used to treat ANY ONE of the following?
Anismus
Chronic motor tic disorder; (e.g., de la Tourette syndrome)
Chronic paralytic strabismus except when used with surgical repair to reduce antagonist contracture
Conditions in an individual who is pregnant or nursing
Duane's syndrome with lateral rectus weakness
Facial wrinkles
Gastroparesis
Hirschsprung’s disease
Myofascial pain syndrome
Occipital neuralgia
Prevention of pain associated with breast reconstruction after mastectomy
Restrictive strabismus
Secondary strabismus caused by prior surgical over-recession of the antagonist
Strabismus deviations over 50 prism diopters
Stuttering and/or any other vocal tremors
Temporomandibular joint disease
Treatment of headache or migraine
Treatment of hyperhidrosis adequately managed with topical agents and without associated functional impairment or medical complications
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Does the individual have a diagnosis of ANY ONE of the following?
Achalasia
Cervical dystonia
Chronic anal fissure
Hereditary spastic paraplegia
Idiopathic torsion dystonia
Infantile cerebral palsy, spastic
Organic writer's cramp
Orofacial dyskinesia
Oromandibular dystonia
Spasmodic dysphonia
Spasmodic torticollis
Spastic hemiplegia
Symptomatic torsion dystonia
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Is the agent requested botulinum toxin type A (e.g., onabotulinumtoxinA [Botox®], abobotulinumtoxinA [Dysport®], incobotulinumtoxinA [Xeomin®])?
If yes, go to question #4
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of blepharospasm, upper limb spasticity or a cranial nerve VII disorder (e.g., hemifacial spasms)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Does the individual have a diagnosis of strabismus with ALL of the following?
Conditions associated with dystonia
ABSENCE of ALL of the following:
Duane’s syndrome with lateral rectus weakness
Restrictive strabismus
Strabismus secondary to prior surgical over-recession of the antagonist
Strabismus deviations more than 50 prism diopters
Chronic paralytic strabismus except when used with surgical repair to reduce antagonist contracture
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Does the individual have a diagnosis of severe primary axillary or palmar hyperhidrosis with ALL of the following?
Treatment is not adequately managed with topical agents
The condition causes ANY ONE of the following:
Functional impairment
Medical complications
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have a diagnosis of urinary incontinence with ALL of the following?
Individual has undergone urodynamic studies with diagnosis of idiopathic detrusor overactivity (IDO)
Anticholinergic therapy has failed to provide adequate control
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #8
Does the individual have a diagnosis of chronic migraine headaches with ALL of the following?
No prior treatment with botulinum toxin
Headaches occur fifteen days or more per month
Headaches last four hours a day or longer
Headaches are experienced for 3 months or more
Symptoms persist despite adequate trials of a minimum of 2 agents from different classes used in the treatment of chronic migraines (e.g., ergot alkaloids, antidepressants, antihypertensives, antiepileptics), unless the individual has contraindications to such medications
If yes, this satisfies medical necessity and medical appropriateness criteria for a 6 month trial of therapy
If no, go to question #9
Is the request for continuation of therapy after a 6-month trial of botulinum toxin for the prevention of chronic migraines with ANY ONE the following outcomes?
Frequency reduced by at least 7 days per month
Duration of headache reduced by at least 100 hours per month
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.