Botulinum Toxin Agents – BOTOX (onabotulinumtoxinA), DAXXIFY (daxibotulinumtoxinA-Ianm), DYSPORT (abobotulinumtoxinA), MYBLOC (rimabotulinumtoxinB), XEOMIN (incobotulinumtoxinA)

Medical Administration 

Diagnosis considered for coverage:

Botox

  1. Overactive Bladder: Indicated for the treatment of overactive bladder (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.
  2. Detrusor Overactivity associated with a Neurologic Condition: Indicated 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 anticholinergic medication.
  3. Neurogenic Detrusor Overactivity (NDO): Indicated for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients 5 years of age and older who have an inadequate response to or are intolerant of anticholinergic medication.
  4. Chronic Migraine: Indicated for prophylaxis of headaches in adult patients with chronic migraine (≥ 15 days per month with headaches lasting 4 hours a day or longer).
  5. Spasticity: Indicated for the treatment of spasticity in patients 2 years of age and older.
  6. Cervical Dystonia (Spasmodic Torticollis): Indicated for the treatment of cervical dystonia in adult patients, to reduce the severity of abnormal head position and neck pain.
  7. Primary Axillary Hyperhidrosis: Indicated for the treatment of severe axillary hyperhidrosis that is inadequately managed by topical agents in adult patients.
  8. Blepharospasm: Indicated for the treatment of blepharospasm associated with dystonia in patients 12 years of age and older.
  9. Strabismus: Indicated for the treatment of strabismus in patients 12 years of age and older.

*Limitations of Use:

  • Safety and effectiveness of BOTOX have not been established for:
    • Prophylaxis of episodic migraine (14 headache days or fewer per month)
    • Treatment of hyperhidrosis in body areas other than axillary

Daxxify

  1. Cervical Dystonia: Indicated for the treatment of cervical dystonia in adult patients. 

Dysport

  1. Cervical Dystonia: Indicated for the treatment of adults with cervical dystonia
  2. Spasticity: Indicated for the treatment of spasticity in patients 2 years of age and older.

Myobloc

  1. Cervical Dystonia: Indicated for treating cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia in adults
  2. Sialorrhea: Indicated for the treatment of chronic sialorrhea in adults

Xeomin

  1. Blepharospasm: Indicated for the treatment of blepharospasm in adults
  2. Cervical Dystonia: Indicated for the treatment of cervical dystonia in adults
  3. Sialorrhea: Indicated for the treatment of chronic sialorrhea in patients 2 years of age and older
  4. Upper Limb Spasticity: Indicated for the treatment of upper limb spasticity in adults and pediatric patients 2 to 17 years of age, excluding spasticity caused by cerebral palsy
Coverage Criteria:
  1. For the diagnosis of neuromuscular or autonomic disorders:

    • Dose does not exceed the FDA max; AND

    • Diagnosis of one of the following:

      • For Botox, Xeomin: Blepharospasm associated with dystonia (e.g., benign essential blepharospasm)

      • For Botox, Daxxify, Dysport, Myobloc, Xeomin: Cervical dystonia

      • For Botox, Dysport, Xeomin: Spasticity (Xeomin only: excluding spasticity caused by cerebral palsy)

      • For Botox: Strabismus

      • For Botox: VII cranial nerve disorders (hemifacial spasms)

  2. For the diagnosis of primary axillary hyperhidrosis (Botox only):

    • Dose does not exceed the FDA max; AND

    • Diagnosis of primary axillary hyperhidrosis; AND

    • One of the following:

      • Score of 3 or 4 on the Hyperhidrosis Disease Severity Scale (HDSS)

      • Skin maceration with secondary infection; AND

    • Trial and failure, contraindication, or intolerance to topical prescription strength drying agents [e.g., Drysol, Xerac AC (aluminum chloride hexahydrate)]; AND

    • Botox will not be used in combination with Qbrexa

  3. For the diagnosis of chronic migraine (Botox only):

    • Dose does not exceed the FDA max; AND

    • Diagnosis of chronic migraines; AND

    • Prescribed by or in consultation with a Neurologist, Pain specialist, or Headache specialist; AND

    • Patient is 18 years of age or older; AND

    • Patient has greater than or equal to 15 headache days a month, of which at least 8 must be migraine days for at least 3 months; AND

    • Documented inadequate response (minimum two-month trial) to at least TWO prophylactic medications used for migraine headaches, each from a different pharmacologic class supported by the American Academy of Neurology, American Headache Society (AAN/AHS), or a contraindication to all medications listed for migraine headache prophylaxis:

      • Antiepileptic drugs (i.e., divalproex sodium, sodium valproate, topiramate, carbamazepine)

      • Beta-blockers (i.e., metoprolol, propranolol, timolol, atenolol, nadolol, nebivolol, pindolol)

      • Antidepressants (i.e., amitriptyline, venlafaxine)

      • Blood pressure drugs (i.e., lisinopril, candesartan)

      • Alpha-agonists (i.e., clonidine, guanfacine)

      • Antihistamines (i.e., cyproheptadine)

  4. For the diagnosis of urinary incontinence associated with a neurologic condition or overactive bladder with symptoms or neurogenic detrusor overactivity (Botox only):

    • Dose does not exceed the FDA max; AND

    • Prescribed by or in consultation with a urologist; AND

    • One of the following conditions:

      • Urinary incontinence that is associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis)

      • Overactive bladder with symptoms (e.g., urge urinary incontinence, urgency, and frequency)

      • Neurogenic detrusor overactivity (NDO); AND

    • Trial and failure, contraindication, or intolerance to at least one oral anticholinergic (antispasmodic or antimuscarinic) agent [e.g., Bentyl (dicyclomine), Donnatal (atropine/ scopolamine/ hyoscyamine/ phenobarbital), Levsin/Levsinex (hyoscyamine), Ditropan (oxybutynin), Enablex (darifenacin), or VESIcare (solifenacin)]; AND

    • Patient is routinely performing clean intermittent self-catheterization (CIC) or is willing/able to perform CIC if the patient has post-void residual (PVR) urine volume greater than 200 mL

  5. For the diagnosis of chronic sialorrhea (Myobloc and Xeomin only)

    • Dose does not exceed the FDA max; AND

    • Diagnosis of chronic sialorrhea

Reauthorization Criteria:
  1. For the diagnosis of neuromuscular or autonomic disorders (Botox, Daxxify, Dysport, Myobloc, Xeomin):

    • Dose does not exceed the FDA max; AND

    • Documentation of positive clinical response to therapy; AND

    • At least 3 months have or will have elapsed since the last treatment

  2. For the diagnosis of primary axillary hyperhidrosis (Botox only):

    • Dose does not exceed the FDA max; AND

    • At least a 2-point improvement in HDSS; AND

    • At least 3 months have or will have elapsed since the last series of injections

  3. For the diagnosis of chronic migraine (Botox only):

    • Dose does not exceed the FDA max; AND

    • Patient has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity; AND

    • Use of acute migraine medications (e.g., NSAIDs, triptans) has decreased since the start of therapy; AND

    • Patient continues to be monitored for medication overuse headache (MOH)

  4. For the diagnosis of urinary incontinence associated with a neurologic condition or overactive bladder with symptoms or neurogenic detrusor overactivity (Botox only):

    • Dose does not exceed the FDA max; AND

    • Documentation of positive clinical response to therapy; AND

    • At least 3 months have or will have elapsed since the last treatment

  5. For the diagnosis of chronic sialorrhea (Myobloc and Xeomin only)

    • Dose does not exceed the FDA max; AND

    • Documentation of positive clinical response to therapy

    • At least 3 months have or will have elapsed since the last treatment

Coverage Duration:
  1. For the diagnosis of neuromuscular or autonomic disorders (Botox, Daxxify, Dysport, Myobloc, Xeomin):

    • Initial: 3 months

    • Reauthorization: 3 months

  2. For the diagnosis of primary axillary hyperhidrosis (Botox only):

    • Initial: 1 treatment

    • Reauthorization: 1 treatment

  3. For the diagnosis of chronic migraines (Botox only):

    • Initial: 3 months

    • Reauthorization: 3 months

  4. For the diagnosis of urinary incontinence associated with a neurologic condition or overactive bladder with symptoms or neurogenic detrusor overactivity (Botox only):

    • Initial: 3 months

    • Reauthorization: 3 months

  5. For the diagnosis of chronic sialorrhea (Myobloc and Xeomin only)

Authorization is not covered for the following:

The following conditions, and other uses of this drug for indications not listed in this policy, do not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

  • Cosmetic - wrinkles
  • Chronic motor tic disorders
  • Tics associated with Tourette’s Syndrome
  • Temporomandibular joint disorder (TMJD or TMD), or TMJ syndrome
  • Parkinson's Disease
  • Focal Lower Limb Dystonia
  • Tardive Dyskinesia
  • Other forms of smooth muscle spasms not specifically addressed in the policy
Additional Information:
  • Dosing:

    • Indications-specific dosage and administration recommendations should be followed

    • When initiating treatment, the lowest recommended dose should be used

    • In treating adult patients for one or more indications, the maximum cumulative dose should not exceed 400 Units, in a 3-month interval

    • In treating pediatric patients, the total dose should not exceed the lower of 10 Units/kg body weight or 340 Units, in a 3-month interval

  • Administration:

    • Potency units of Botox for injection are specific to the preparation and assay method utilized.  They are not interchangeable with other preparations of botulinum toxin products

  • Drug-Drug Interactions:

    • Patients receiving concomitant treatment of Botox and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of Botox may be potentiated

Policy Updates:
  • 06/1/2024 - Updated policy to include Daxxify for diagnosis of cervical dystonia
  • 11/15/2022 – Updated policy and format.
  • 10/19/2021 - Criteria now allowing combination with calcitonin gene-related peptide (CGRP) antagonist therapy removed
  • 06/08/2017 - Initial policy entry
References:
  1. Botox Prescribing Information. Allergan, Inc. Madison, NJ. February 2021.
  2. AHFS Drug Information (2005) website. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/pdh_f/130028?searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3DBotox%26t%3Dname%26va%3DBotox. Accessed August 14, 2020.
  3. DRUGDEX System [Internet database]. Greenwood Village, CO: Thomson Micromedex. Updated periodically. Accessed August 14, 2020.
  4. Lowe NJ, Glaser DA, Eadie N, Daggett S, Kowalski JW, Lai PY. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol. 2007;56:604-611.
  5. 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;323:596-9.
  6. Vaezi MF, Pandolfino JE, Vela MF. American College of Gastroenterology Practice Parameter Committee. Diagnosis and management of achalasia. Am J Gastroenterol advance online publication, 23 July 2013.
  7. Pasricha PJ, et al. Intrasphincteric botulinum toxin for the treatment of achalasia. N Engl J Med 1995;332:774-8.
  8. American Society of Colon and Rectal Surgeons. Practice Parameters for the Management of Anal Fissures (3rd Revision). Dis Colon Rectum 2010; 53: 1110–1115.
  9. Brisinda G, et al. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 1999;341:65-9.
  10. Ney JP, Difazio M, Sichani A, Monacci W, Foster L, Jabbari B. Treatment of chronic low back pain with successive injections of botulinum toxin A over 6 months: a prospective trial of 60 patients. Clin J Pain 2006;22(4):363-369.
  11. MayoClinic. Back pain. Available at: www.mayoclinic.com. Accessed August 14, 2020.
  12. Naumann M, So Y, Argoff CE et al. Assessment: botulinum neurotoxin in the treatment of autonomic disorder and pain (an evidence-based review): report of the Therapeutics and Assessment Subcommittee of the American Academy of Neurology. Neurology 2008;70:1707-1714.
  13. Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalagia. 2010;30:793-803.
  14. Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalagia. 2010;30:804-814.
  15. Dodick DW, Turkel CC, DeGryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50:921-936.
  16. Per clinical consultation with neurologist, January 7, 2011.
  17. Silberstein SD, Holland S, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. 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 Apr 24;78(17):1337-45.
  18. Loder E, Burch R, Rizzoli P.The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison With Other Recent Clinical Practice Guidelines. Headache 2012;52:930-945.
  19. Per clinical consultation with neurologist, July 20, 2015.
  20. International Headache Society (IHS); Headache Classification Committee. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33: 629-808.
  21. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10;86(19):1818-26.
  22. Per Clinical Consultation with a Neurologist. January 24th, 2018.
  23. National Institute for Health and Care Excellence. Management of migraine (with or without aura). April 17th, 2018. Available at: https://pathways.nice.org.uk/pathways/headaches/management-of-migraine-with-or-without-aura#path=view%3A/pathways/headaches/management-of-migraine-with-or-without-aura.xml&content=view-node%3Anodes-prophylactic-treatment. Accessed August 14, 2020.
  24. Botox Cosmetic Prescribing Information. Allergan, Inc. Irvine, CA. July 2020.
  25. Dysport Prescribing Information. Ipsen Biopharmaceuticals, Inc. Cambridge, MA. July 2020.
  26. Truong D, Duane DD, Jankovic J, et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study. Mov Disord. 2005;20(7):783-791.
  27. Simpson D, Hallett M, Ashman E et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. Neurology. 2016;86(19):1818-1826.
  28. Myobloc Prescribing Information. Solstice Neurosciences, LLC. Louisville, KY. March 2021.
  29. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May;86(19):1818-26.
  30. Xeomin prescribing information. Merz Pharmaceuticals, LLC. Raleigh, NC. August 2021.
  31. Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64:1949-1951.
  32. Kanovsky P, Slawek J, Denes Z, et al. Efficacy and safety of treatment with incobotulinum toxin A (botulinum neurotoxin type A free from complexing proteins; NT 201) in post-stroke upper limb spasticity. J Rehabil Med 2011; 43(6):486-492.
  33. Jankovic J, Comella C, Hanschmann A, et al. Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm-a randomized trial. Mov Disord 2011; 26(8):1521-1528.
  34. Daxxify Prescribing Information. Revance Therapeutics, Inc. Newark, CA. August 2023

   

Last review date: June 1, 2024