DYSPORT, AbobotulinumtoxinA Form

AbobotulinumtoxinA (Dysport®) is an acetylcholine release inhibitor and a neuromuscular blocking agent. Prophylaxis X X X X X X X X Adults Pediatrics Treatment FDA Approved Indication(s) Indication Cervical dystonia (focal dystonia) Upper/lower limb spasticity (includes CP)
Off-Label Uses Overactive bladder (OAB) Urinary incontinence Migraine Axillary hyperhidrosis Blepharospasm (focal dystonia) Strabismus Sialorrhea Laryngeal dystonia Oromandibular dystonia Upper extremity dystonia Upper extremity essential tremor Esophageal achalasia HD and IAS achalasia Chronic anal fissure Abbreviations: cerebral palsy (CP); Hirschsprung disease (HD), internal anal sphincter (IAS) achalasia. *See criteria set entitled Focal Dystonia and Essential Tremor X X X X X X X X X X X X X X X X X X X X X X X X X X Dysport is indicated: • For the treatment of cervical dystonia (CD) in adults • For the treatment of spasticity in patients 2 years of age and older • For 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 [benefit exclusion] Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
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CLINICAL POLICY
AbobotulinumtoxinA Index I. Initial Approval Criteria A. Cervical Dystonia (focal dystonia) B. Upper and Lower Limb Spasticity (includes cerebral palsy) C. Overactive Bladder and Urinary Incontinence (off-label) D. Chronic Migraine (off-label) E. Axillary Hyperhidrosis (excessive underarm sweating) (off-label) F. Blepharospasm (focal dystonia - abnormal eyelid muscle contraction) (off-label) G. Strabismus (eye misalignment) (off-label) H. Sialorrhea (off-label) I. Focal Dystonia and Essential Tremor (off-label) J. Esophageal Achalasia (off-label) K. Hirschsprung Disease and Internal Anal Sphincter Achalasia (off-label) L. Chronic Anal Fissure (off-label) M. Other diagnoses/indications II. Continued Approval Criteria A. Chronic Migraine B. Esophageal Achalasia C. Cervical Dystonia and Upper/Lower Limb Spasticity D. All Other Indications in Section I E. Other diagnoses/indications III. Diagnoses/Indications for which coverage is NOT authorized:
IV. Appendices V. Dosage and Administration VI. Product Availability VII. References It is the policy of health plans affiliated with Centene Corporation® that Dysport is medically necessary when one of the following criteria are met:
I. Initial Approval Criteria
A. Cervical Dystonia (focal dystonia) (must meet all):

1. Diagnosis of CD;
   2. Prescribed by or in consultation with a neurologist, orthopedist, or physiatrist;
   3. Age ≥ 18 years;
   4. Member is experiencing involuntary contractions of the neck and shoulder muscles (e.g., splenius, sternocleidomastoid, levator scapulae, scalene, trapezius, semispinalis capitis) resulting in abnormal postures or movements of the neck, shoulders or head;
2. Contractions are causing pain and functional impairment;
   
   6. Dysport is not prescribed concurrently with other botulinum toxin products;
   7. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;

3. Treatment plan details number of Units per indication and treatment session;

   9. Dose does not exceed 500 Units per treatment session. Approval duration:
      Medicaid/HIM – 12 months Page 2 of 20

   CLINICAL POLICY
   AbobotulinumtoxinA Commercial – 6 months or to member’s renewal date, whichever is longer B. Upper and Lower Limb Spasticity (includes cerebral palsy) (must meet all):

4. Diagnosis of upper or lower limb spasticity (e.g., associated with paralysis, central nervous system demyelinating diseases such as multiple sclerosis, cerebral palsy, stroke);
5. Prescribed by or in consultation with a neurologist, orthopedist, or physiatrist;
   3. Age ≥ 2 years;
   4. Dysport is not prescribed concurrently with other botulinum toxin products;
   5. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
6. Treatment plan details number of Units per indication and treatment session;
   7. Request meets one of the following (a or b): a. Age ≥ 18 years (i, ii, or iii): i. Upper limb spasticity: Dose does not exceed 1,000 Units per treatment session; ii. Lower limb spasticity: Dose does not exceed 1,500 Units per treatment session; iii. Upper and lower limb spasticity: Dose does not exceed 1,500 Units per treatment session staying within per limb dosing guidelines; b. Age ≥ 2 years to < 18 years (i, ii, or iii): i. Upper limb spasticity: Dose does not exceed the lower of 16 Units/kg or 640 Units; ii. Lower limb spasticity: Dose does not exceed the lower of 15 Units/kg (one limb), 30 Units/kg (two limbs), or 1,000 Units per treatment session; iii. Upper and lower limb spasticity: Dose does not exceed the lower of 30 Units/kg or 1,000 Units per treatment session staying within per limb dosing guidelines. Approval duration:
      Medicaid/HIM – 12 months
      Commercial – 6 months or to member’s renewal date, whichever is longer C. Overactive Bladder and Urinary Incontinence (off-label) (must meet all):
7. Diagnosis of one of the following (a or b): a. OAB and member’s history is positive for urinary urgency, frequency, and nocturia with or without incontinence;
   b. Urinary incontinence and member’s history is positive for an associated neurologic condition (e.g., spinal cord injury, multiple sclerosis);
8. Prescribed by or in consultation with a neurologist or urologist;
   3. Age ≥ 18 years;
   4. Failure of one of the following (a or b), each used for at least 30 days, unless clinically significant adverse effects are experienced or all are contraindicated (see Appendix B); a. Two anticholinergic agents;
      b. One oral beta-3 agonist medication;

9. Dysport is not prescribed concurrently with other botulinum toxin products;
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   CLINICAL POLICY
   AbobotulinumtoxinA

10. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
11. Treatment plan details number of Units per indication and treatment session;
    8. Dose does not exceed 250 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer D. Chronic Migraine (off-label) (must meet all):
12. Diagnosis of chronic migraine (i.e., ≥ 15 headache days per month for at least 3 months with headache lasting 4 hours a day or longer);
13. Prescribed by or in consultation with a neurologist or pain specialist;
    3. Age ≥ 18 years;
    4. Failure of at least 2 of the following oral migraine preventative therapies, each for 8 weeks and from different therapeutic classes, unless clinically significant adverse effects are experienced or all are contraindicated (a, b, or c): a. Antiepileptics (e.g., divalproex sodium, sodium valproate, topiramate); b. Beta-blockers (e.g., metoprolol, propranolol, timolol); c. Antidepressants (e.g., amitriptyline, venlafaxine);
14. Dysport is not prescribed concurrently with injectable calcitonin gene-related peptide (CGRP) inhibitors (e.g., Aimovig®, Ajovy®, Emgality®);
15. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    7. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
16. Treatment plan details number of Units per indication and treatment session;
    9. Dose does not exceed 250 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer E. Primary Axillary Hyperhidrosis (excessive underarm sweating) (off-label) (must meet all):
    10. Diagnosis of primary axillary hyperhidrosis;
    11. Prescribed by or in consultation with a neurologist or dermatologist;
    12. Age ≥ 18 years;
    13. Failure of a 6-month trial of topical aluminum chloride, unless contraindicated or clinically significant adverse effects are experienced;
17. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;

18. Treatment plan details number of Units per indication and treatment session;

    8. Dose does not exceed 200 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer Page 4 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA F. Blepharospasm (focal dystonia - abnormal eyelid muscle contraction) (off-label) (must meet all):

    1. Diagnosis of blepharospasm;
    2. Prescribed by or in consultation with a neurologist or ophthalmologist;
    3. Age ≥ 18 years;
    4. Member is experiencing significant disability in daily functional activities due to interference with vision;
19. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
20. Treatment plan details number of Units per indication and treatment session;
    8. Dose does not exceed 120 Units per treatment session.
       Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer G. Strabismus (eye misalignment) (off-label) (must meet all):
21. Diagnosis of one of the following (a, b, or c): a. Vertical strabismus (superior and inferior rectus muscles, superior and inferior oblique muscles); b. Horizontal strabismus (medial and lateral rectus muscles) (i or ii): i. Horizontal strabismus < 20 prism diopters; ii. Horizontal strabismus 20 to 50 prism diopters; c. Persistent sixth cranial nerve (VI; abducens nerve) palsy of ≥ one month involving the lateral rectus muscle;
22. Prescribed by or in consultation with a neurologist or ophthalmologist;
    3. Age ≥ 12 years;
    4. Dysport is not prescribed concurrently with other botulinum toxin products;
    5. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
23. Treatment plan details number of Units per indication and treatment session;
    7. Dose does not exceed 20 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer H. Chronic Sialorrhea (off-label) (must meet all):
24. Diagnosis of chronic sialorrhea for at least the last three months due to one of the following (a or b): a. Underlying neurologic disorder (e.g., Parkinson disease, atypical parkinsonism, stroke, traumatic brain injury, cerebral palsy, amyotrophic lateral sclerosis); b. Craniofacial abnormality (e.g., Goldenhar syndrome);

25. Prescribed by or in consultation with a neurologist or physiatrist;

    3. Age ≥ 18 years;
    4. Failure of at least one anticholinergic drug (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated; Page 5 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA

26. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 16 weeks;
27. Treatment plan provided detailing number of Units per indication and treatment session;
28. Dose does not exceed 250 Units per treatment session; Approval duration:
    Medicaid/HIM – 12 months
    Commercial – 6 months or to member’s renewal date, whichever is longer I. Focal Dystonia and Essential Tremor (off-label) (must meet all):
29. Diagnosis of one of the following (a, b, c, or d): a. Laryngeal dystonia;
    b. Oromandibular dystonia (OMD); c. Upper extremity (UE) dystonia; d. UE essential tremor;
30. Prescribed by or in consultation with a neurologist, ENT specialist, orthopedist, or physiatrist;
31. Age meets one of the following (a or b): a. For upper extremity dystonia: Age ≥ 2 years; b. For all other indications: Age ≥ 18 years;
32. For UE dystonia: Failure of a trial of carbidopa/levodopa or trihexyphenidyl (see Appendix B), unless clinically significant adverse effects are experienced or both are contraindicated;
33. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
34. Treatment plan details number of Units per indication and treatment session;
    8. Request meets one of the following (a, b, or c): a. Laryngeal dystonia: Dose does not exceed 45 Units per treatment session; b. OMD: Dose does not exceed 100 Units per treatment session; c. UE dystonia, UE essential tremor: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use and member age (prescriber must submit supporting evidence; Units per treatment session does not exceed the lower of 16 Units/kg body weight or 640 Units for pediatrics, or 1,000 Units for adults). Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer J. Esophageal Achalasia (off-label) (must meet all):

35. Diagnosis of esophageal achalasia;

    2. Prescribed by or in consultation with a gastroenterologist;
    3. Age ≥ 18 years;
    4. Member is not a candidate for pneumatic dilation or laparoscopic surgical myotomy (e.g., due to age, comorbidity); Page 6 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA

36. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
37. Treatment plan details number of Units per indication and treatment session;
    8. Dose does not exceed 250 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer K. Hirschsprung Disease, Internal Anal Sphincter Achalasia (off-label) (must meet all):
38. Diagnosis of one of the following (a or b):
    a. Hirschsprung disease (HD) and (i or ii): i. Member has an HD subtype known as ultra-short segment HD; ii. Dysport is prescribed for constipation post-surgery; b. Internal anal sphincter (IAS) achalasia;
39. Prescribed by or in consultation with a gastroenterologist;
    3. Age ≥ 3 years;
    4. Failure of a trial of stool softeners and laxatives (see Appendix B), unless clinically adverse effects are experienced or all are contraindicated;
40. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    6. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
41. Treatment plan details number of Units per indication and treatment session;
    8. Dose does not exceed 200 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer L. Chronic Anal Fissure (off-label) (must meet all):
42. Diagnosis of chronic anal fissure;
    2. Prescribed by or in consultation with a gastroenterologist or colorectal surgeon;
    3. Age ≥ 18 years;
    4. Failure of nitroglycerin ointment, unless contraindicated or clinically significant adverse effects are experienced;
43. Failure of one of the following (a or b), unless contraindicated or clinically significant adverse effects are experienced (see Appendix B):
    a. Oral/topical nifedipine; b. Oral/topical diltiazem;
44. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    7. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;

45. Treatment plan details number of Units per indication and treatment session;

    9. Dose does not exceed 100 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer Page 7 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA M. Other diagnoses/indications (must meet 1 or 2):

46. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
47. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Approval
    A. Chronic Migraine (must meet all):
48. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
49. If receipt of ≥ 2 Dysport treatment sessions, member has experienced and maintained a 30% reduction in monthly migraine headache frequency from baseline;
    3. Dysport is not prescribed concurrently with injectable CGRP inhibitors (e.g., Aimovig, Ajovy, Emgality);
50. Dysport is not prescribed concurrently with other botulinum toxin products;
    
    5. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
51. Treatment plan details number of Units per indication and treatment session;
    7. If request is for a dose increase, new dose does not exceed 250 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months
       Commercial – 6 months or to member’s renewal date, whichever is longer B. Esophageal Achalasia (must meet all):

52. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 8 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

    2. Member is responding positively to therapy;
    3. Dysport is not prescribed concurrently with other botulinum toxin products;
    4. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
53. If member has previously received ≥ 2 Dysport treatment sessions for esophageal achalasia, it has been at least 24 weeks since the last treatment session;
    
    6. Treatment plan details number of Units per indication and treatment session;
    7. If request is for a dose increase, new dose does not exceed 250 Units per treatment session. Approval duration:
       Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer C. Cervical Dystonia and Upper/Lower Limb Spasticity (must meet all):
54. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy;
    3. Dysport is not prescribed concurrently with other botulinum toxin products;
    4. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;

55. Treatment plan details number of Units per indication and treatment session;

    6. If request is for a dose increase, request meets one of the following (a or b): a. Age ≥ 18 years (i, ii, iii, or iv): i. CD: Dose does not exceed an increase of 250 Units per treatment session up to a total of 1,000 Units per treatment session; ii. Upper limb spasticity: Dose does not exceed 1,000 Units per treatment session; iii. Lower limb spasticity: Dose does not exceed 1,500 Units per treatment session; iv. Upper and lower limb spasticity: Dose does not exceed 1,500 Units per treatment session staying within per limb dosing guidelines; b. Age ≥ 2 years to < 18 years (i, ii, or iii): i. Upper limb spasticity: Dose does not exceed the lower of 16 Units/kg or 640 Units; ii. Lower limb spasticity: Dose does not exceed the lower of 15 Units/kg (one limb), 30 Units/kg (two limbs), or 1,000 Units per treatment session; iii. Upper and lower limb spasticity: Dose does not exceed the lower of 30 Units/kg or 1,000 Units per treatment session staying within per limb dosing guidelines. Page 9 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA Approval duration:
    Medicaid/HIM – 12 months
    Commercial – 6 months or to member’s renewal date, whichever is longer
    D. All Other Indications in Section I (off-label) (must meet all):

56. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy;
    3. Dysport is not prescribed concurrently with other botulinum toxin products;
    4. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
57. Treatment plan details number of Units per indication and treatment session;
    6. If request is for a dose increase, request meets one of the following: a. OAB/urinary incontinence, sialorrhea: Dose does not exceed 250 Units per treatment session; b. Axillary hyperhidrosis, HD, IAS achalasia: Dose does not exceed 200 Units per treatment session; c. Blepharospasm: Dose does not exceed 120 Units per treatment session; d. Strabismus: Dose does not exceed 20 Units per treatment session; e. Laryngeal dystonia: Dose does not exceed 45 Units per treatment session; f. OMD, chronic anal fissure: Dose does not exceed 100 Units per treatment session; Approval duration:
       Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer
       E. Other diagnoses/indications (must meet 1 or 2):
58. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

59. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line Page 10 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    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 policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Cosmetic treatment of hyperfunctional wrinkles of the upper face including glabellar frown lines, deep forehead wrinkles and periorbital wrinkles (crow’s feet); C. Episodic migraine (≤ 14 headache days per month): Safety and efficacy have not been established per the package insert;
    D. Total treatment dose per session does not exceed the lower of 30 Units/kg body weight or 1,000 Units for pediatrics and 1,500 Units for adults. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CD: cervical dystonia CGRP: calcitonin gene-related peptide FDA: Food and Drug Administration HD: Hirschsprung disease IAS: internal anal sphincter MS: multiple sclerosis OAB: overactive bladder OMD: oromandibular dystonia SCI: spinal cord injury UE: upper extremity Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Overactive bladder, urinary incontinence oxybutynin (Ditropan/XL, Gelnique) (anticholinergic agent) • Immediate-release tablets: 5 mg orally two to three times daily • Extended-release tablets: 5-10 mg orally once daily • Topical gel: Apply contents of one sachet topically once daily • Immediate- release: 20 mg/day • Extended- release: 30 mg/day • Gel: one sachet/day tolterodine tartrate (Detrol/LA) (anticholinergic agent) • Immediate-release tablets: 2 mg orally 4 mg/day twice daily • Extended-release tablets: 4 mg orally Myrbetriq (mirabegron)
    (beta-3 agonist) once daily 25 mg orally once daily 50 mg/day Page 11 of 20

    Dose Limit/ Maximum Dose Refer to prescribing information One application/day See regimen information See regimen information CLINICAL POLICY
    AbobotulinumtoxinA Drug Name Dosing Regimen Refer to prescribing information for dosing regimens. Chronic migraine Examples of oral migraine preventive therapies -
    • Anticonvulsants: divalproex (Depakote®), topiramate (Topamax®) • Beta blockers: propranolol (Inderal®), metoprolol (Lopressor®), timolol
    • Antidepressants/tricyclic antidepressants: amitriptyline (Elavil®), venlafaxine (Effexor®) Apply topically once daily Primary axillary hyperhidrosis Drysol® (aluminum chloride) Sialorrhea: examples of anticholinergic drugs glycopyrrolate (Glycate® oral tablets, Cuvposa® oral solution) • Adults: 1 mg PO TID
    (Off-label: Lakraj 2013) • Pediatrics: chronic drooling: children ≥ 3 years and adolescents ≤ 16 years: oral solution (Cuvposa): 20 mcg/kg/dose 3 times daily, titrate in increments of 20 mcg/kg/dose every 5 to 7 days as tolerated to response up to a maximum dose of 100 mcg/kg/dose 3 times daily; not to exceed 1,500 to 3,000 mcg/dose. (FDA labeled) Mean doses of 3.8 mg/day have been used in adults and pediatrics ≥ 4 years. Benztropine typically is administered in divided doses titrating up as needed.
    (Off-label - Sridharan 2018, Lakraj 2013; Micromedex, package insert) 25 mg/100 mg PO QD, and increase by 1 tablet every 3 to 5 days. 1,200 mg/day of levodopa 30 mg PO QD 30 mg/day 5 to 15 mg PO or 10 mg PR QD 30 mg/day Page 12 of 20 benztropine mesylate (oral tablets - 0.5 mg, 1 mg, 2 mg) Dystonia carbidopa/levodopa (Sinemet®, Duopa®, Rytary®) trihexyphenidyl HD, IAS achalasia Dulcolax® (bisacodyl)

    CLINICAL POLICY
    AbobotulinumtoxinA Drug Name Dosing Regimen MiraLax® (Polyethylene glycol 3350) Colace® (Docusate sodium) Chronic anal fissure nitroglycerin 0.2% ointment (Rectiv®) nifedipine or diltiazem (oral or topical ointment/gel-compounded) 17 grams of polyethylene glycol 3350 in 4-8 oz water by mouth once daily 50-200 mg PO QD-QID 15 to 30 mg (2.5 to 5 cm as squeezed from the tube, about 1 to 2 inches), applied topically to skin every 8 hours while awake and at bedtime; application frequency may be increased to every 6 hours if needed; alternatively, a regimen providing a 12-hour nitrate-free interval may be used; apply dosage once each morning, then 6 hours later PO: At provider discretion
    Intra-anal: 0.2% ointment or gel, applied around fissure(s) 2 times daily for 6-8 weeks Dose Limit/ Maximum Dose 17 grams/day 200 mg/day 75 mg (12.5 cm as squeezed from the tube)/day Varies 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. Appendix C: Contraindications and Boxed Warnings • Contraindication(s): o Hypersensitivity to any botulinum toxin preparation or excipients o Hypersensitivity to cow’s milk protein o Infection at the proposed injection site • Boxed warning(s): distant spread of toxin effect Appendix D: Botulinum Toxin Product Interchangeability • Potency Units of Dysport are not interchangeable with other botulinum toxin product preparations (e.g., Botox®, Myobloc®, Xeomin®). Appendix E: Guideline Support for Botulinum Toxin Use Indication Focal Dystonia and Essential Tremor, and Headache
    Blepharospasm, cervical dystonia, adult spasticity, and headache Migraine prevention Guideline Academy of Neurology (2016) Laryngeal dystonia Oromandibular dystonia Focal limb dystonia - UE* American Academy of Neurology and the American Headache Society (Neurology 2012, Headache 2021) American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNS 2018) American Academy of Oral Medicine (2018) American Academy of Neurology (2008) Page 13 of 20

    CLINICAL POLICY
    AbobotulinumtoxinA Indication Essential tremor - UE Sialorrhea OAB/urinary incontinence Guideline American Academy of Neurology (2008, 2011) American Academy of Cerebral Palsy and Developmental Medicine (AACPDM, 2018); International Parkinson and Movement Disorder Society (2018) American Urological Association Society of Urodynamics (2019) Gastrointestinal Conditions (see guidelines for required oral medication information) American College of Gastroenterology (2020) Esophageal achalasia American Pediatric Surgical Association (2017) HD and IAS achalasia American College of Gastroenterology (2021) Chronic anal fissure American Academy of Neurology (AAN) classifies Botox use for hemifacial spasm and motor tics as category C, and notes that data are inadequate to make a recommendation for lower limb dystonia. All other AAN Botox recommendations above are classified as category B - probably effective.
    *Policy criteria requiring failure of oral medication for dystonias are limited to dystonias affecting the limbs (see Cloud and Jinnah, 2010). V. Dosage and Administration
    Indication CD Adult upper and lower limb spasticity Pediatric upper and lower limb spasticity Off-label uses Adults: OAB/ urinary incontinence associated with neurologic condition Adults: chronic migraine Dosing Regimen Divided among affected muscles every 12 weeks: Up to 1,000 Units IM
    Divided among affected muscles every 12 weeks: • Upper limb: Up to 1,000 Units IM
    • Lower limb: Up to 1,500 Units IM
    Upper and lower limbs: Up to 1,500 Units IM staying within per limb guidelines Divided among affected muscles every 12 weeks: • Upper limb: Up to the lower of 16 Units/kg/limb IM or 640 Units IM • Lower limb: Up to the lower of 15 Units/kg/limb IM or 1,000 Units IM • Bilateral lower limb: Up to the lower of 30 Units/kg IM or 1,000 Units IM Upper and lower limbs: Up to the lower of 30 Units/kg IM or 1,000 Units IM staying within per limb guidelines Up to 250 Units IM in the detrusor muscle per treatment session. (Off-label - Irwin 2013) Maximum Dose See dosing regimens for maximum dose Frequency: • Esophageal achalasia: one treatment session every 24 weeks. • All other indications: one treatment session every 12 weeks. Up to 250 Units IM per treatment session. (Off-label - Alipour 2016, Menezes 2007) Page 14 of 20

    Maximum Dose CLINICAL POLICY
    AbobotulinumtoxinA Indication Adults: axillary hyperhidrosis Adults: blepharospasm Adults: strabismus Adults: chronic sialorrhea Adults: laryngeal dystonia Adults: OMD Adults and pediatrics: UE dystonia Adults: UE essential tremor
    Adults: esophageal achalasia Adults and pediatrics: HD, IAS achalasia Adults: chronic anal fissure Dosing Regimen Up to 200 Units IM per treatment session. (Off-label - Clinical Pharmacology, Heckmann 2001) Up to 120 Units SC per treatment session. (Off-label - Hallet 2009, Micromedex, Truong 2008) Up to 20 Units IM per treatment session. (Off-label - Bunting 2013, Talebnejad 2008) Up to 250 Units IM per treatment session. (Off-label - Guidubaldi 2011) Up to 45 Units IM per treatment session. (Off-label - Truong 2006, Guglielmino 2018) Up to 100 Units IM per treatment session. (Off-label - Hallet 2009) Dose is supported by practice guidelines or peer- reviewed literature for the relevant off-label use and member age (prescriber must submit supporting evidence; number of Units per treatment session does not exceed the lower of 16 Units/kg body weight or 640 Units IM for pediatrics, or 1,000 Units IM for adults). Up to 250 Units IM per treatment session. (Off-label - Annese 1999) Up to 200 Units IM per treatment session. (Off-label - Han-Geurts 2014, Roorda 2019) Up to 100 Units IM per treatment session. (Off-label - Pilkington 2018) VI. Product Availability
    Vials: 300 units, 500 units VII.