XEOMIN, IncobotulinumtoxinA Form

IncobotulinumtoxinA (Xeomin®) is an acetylcholine release inhibitor and a neuromuscular blocking agent. X X X X FDA Approved Indication(s) Indication Sialorrhea Upper limb spasticity (includes CP)
Cervical dystonia (focal dystonia) Blepharospasm (focal dystonia) Off-Label Uses Lower limb spasticity Overactive bladder Urinary incontinence Migraine Axillary hyperhidrosis Oromandibular dystonia* Upper extremity dystonia Upper extremity essential tremor Abbreviations: cerebral palsy (CP)
See criteria set entitled Upper and Lower Limb Spasticity *See criteria set entitled Focal Dystonia and Essential Tremor X X X X X X X X Adults Pediatrics Treatment Prophylaxis X X X X X X X X X X X X X X Xeomin is indicated for the treatment or improvement of: • Chronic sialorrhea in patients 2 years of age and older • Upper limb spasticity in adults • Upper limb spasticity in pediatric patients 2 to 17 years of age, excluding spasticity caused by cerebral palsy • Cervical dystonia in adults • Blepharospasm in adults • Temporary improvement in the appearance of moderate to severe glabellar lines with corrugator and/or procerus muscle activity in adults
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 IncobotulinumtoxinA Index I. Initial Approval Criteria A. Chronic Sialorrhea B. Upper and Lower Limb Spasticity (includes cerebral palsy) C. Cervical Dystonia (focal dystonia) D. Blepharospasm (focal dystonia - abnormal eyelid muscle contraction) E. Overactive Bladder and Urinary Incontinence (off-label) F. Chronic Migraine (off-label) G. Axillary Hyperhidrosis (excessive underarm sweating) (off-label) H. Focal Dystonia and Essential Tremor (off-label) I. Other diagnoses/indications II. Continued Approval Criteria A. Chronic Migraine B. All Other Indications in Section I C. 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 Xeomin is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Sialorrhea (must meet all):

1. 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);
2. Prescribed by or in consultation with a neurologist or physiatrist;
   3. Age ≥ 2 years;
   4. Failure of at least one anticholinergic drug (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated;
3. Xeomin 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;
4. Treatment plan provided detailing number of Units per indication and treatment session;

5. Request is for one of the following (a or b): a. For age ≥ 18 years, dose does not exceed 30 Units per parotid gland, 20 Units per submandibular gland, 100 Units per treatment session; b. For age ≥ 2 years, dose does not exceed any of the following (i, ii, iii, iv, v, or vi): i. For body weight 12 kg to < 15 kg, 6 Units per parotid gland, 4 Units per submandibular gland, 20 Units per treatment session; Page 2 of 20

   CLINICAL POLICY IncobotulinumtoxinA ii. For body weight 15 kg to < 19 kg, 9 Units per parotid gland, 6 Units per submandibular gland, 30 Units per treatment session; iii. For body weight 19 kg to < 23 kg, 12 Units per parotid gland, 8 Units per submandibular gland, 40 Units per treatment session; iv. For body weight 23 kg to < 27 kg, 15 Units per parotid gland, 10 Units per submandibular gland, 50 Units per treatment session; v. For body weight 27 kg to < 30 kg, 18 Units per parotid gland, 12 Units per submandibular gland, 60 Units per treatment session; vi. For body weight ≥ 30 kg, 22.5 Units per parotid gland, 15 Units per submandibular gland, 75 Units per treatment session. Approval duration: Medicaid/HIM – 16 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer
   B. Upper and Lower Limb Spasticity (includes cerebral palsy) (must meet all):

6. Diagnosis of upper limb spasticity or lower limb spasticity (e.g., associated with paralysis, central nervous system demyelinating diseases such as multiple sclerosis, cerebral palsy, stroke);
7. Prescribed by or in consultation with a neurologist, orthopedist, or physiatrist;
   3. Member meets one of the following (a or b): a. For upper limb spasticity, age ≥ 2 years; b. For lower limb spasticity, age ≥ 18 years (off-label);
8. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);
9. Xeomin 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;
10. Treatment plan provided detailing number of Units per indication and treatment session;
11. Dose does not exceed 400 Units per treatment session. Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer
    C. Cervical Dystonia (must meet all):
12. 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, shoulder or head;
13. Contractions are causing pain and functional impairment;
    
    6. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);

14. Xeomin is not prescribed concurrently with other botulinum toxin products;
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    CLINICAL POLICY IncobotulinumtoxinA

15. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
16. Treatment plan provided detailing number of Units per indication and treatment session;
17. Dose does not exceed one of the following (a or b): a. Treatment-naïve: 120 Units per treatment session; b. Treatment-experienced: 300 Units per treatment session. Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer
    D. Blepharospasm (focal dystonia - abnormal eyelid muscle contraction) (must meet all):
18. 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. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);
20. Xeomin 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;
21. Treatment plan provided detailing number of Units per indication and treatment session;
22. Dose does not exceed 50 Units per eye per treatment session. Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer
    E. Overactive Bladder and Urinary Incontinence (off-label) (must meet all):
23. 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);
24. Prescribed by or in consultation with a neurologist or urologist;
    3. Age ≥ 18 years;
    4. Failure of a trial of both of the following (a and b), each used for at least 30 days, unless clinically significant adverse effects are experienced or all are contraindicated (see Appendix B); a. At least 2 anticholinergic agents;
       b. Oral beta-3 agonist medication;
25. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);

26. Xeomin is not prescribed concurrently with other botulinum toxin products;
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    CLINICAL POLICY IncobotulinumtoxinA

27. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
28. Treatment plan provided detailing number of Units per indication and treatment session;
29. Dose does not exceed 200 Units per treatment session. Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer F. Chronic Migraine (off-label) (must meet all):
30. 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);
31. 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);
32. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);
33. Xeomin is not prescribed concurrently with injectable calcitonin gene-related peptide (CGRP) inhibitors (e.g., Aimovig®, Ajovy®, Emgality®);
34. Xeomin is not prescribed concurrently with other botulinum toxin products;
    
    8. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 weeks;
35. Treatment plan provided detailing number of Units per indication and treatment session;
36. Dose does not exceed 155 Units per treatment session. Approval duration: Medicaid/HIM – 24 weeks (two 12-week treatment sessions) Commercial – 6 months or to member’s renewal date, whichever is longer G. Primary Axillary Hyperhidrosis (excessive underarm sweating) (off-label) (must meet all):
    
    1. Diagnosis of primary axillary hyperhidrosis;
    2. Prescribed by or in consultation with a neurologist or dermatologist;
    3. Age ≥ 18 years;
    4. Failure of a 6-month trial of topical aluminum chloride, unless contraindicated or clinically significant adverse effects are experienced;
37. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);

38. Xeomin 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; Page 5 of 20

    CLINICAL POLICY IncobotulinumtoxinA

39. Treatment plan provided detailing number of Units per indication and treatment session;
40. Dose does not exceed 100 Units per treatment session. Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer H. Focal Dystonia and Essential Tremor (off-label) (must meet all):
41. 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;
42. Prescribed by or in consultation with a neurologist, ENT specialist, orthopedist, or physiatrist;
43. 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;
44. For upper extremity dystonia: Failure of a trial of carbidopa/levodopa or trihexyphenidyl (see Appendix B), unless clinically significant adverse effects are experienced or both are contraindicated;
45. Failure of Botox® and Dysport®, unless clinically significant adverse effects are experienced or both are contraindicated (see Appendix B);
46. Xeomin 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;
47. Treatment plan provided detailing number of Units per indication and treatment session;
48. Request meets one of the following (a or b): a. OMD: Dose does not exceed 25 Units per treatment session; b. 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 400 Units per treatment session). Approval duration: Medicaid/HIM – 12 weeks (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer I. Other diagnoses/indications (must meet 1 or 2):

49. 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 Page 6 of 20

    CLINICAL POLICY IncobotulinumtoxinA 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

50. 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):
51. 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);
52. If receipt of ≥ 2 Xeomin treatment sessions, member has experienced and maintained a 30% reduction in monthly migraine headache frequency from baseline;
    3. Xeomin is not prescribed concurrently with injectable CGRP inhibitors (e.g., Aimovig, Ajovy, Emgality);
53. Xeomin 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;
54. Treatment plan details number of Units per indication and treatment session;
    7. If request is for a dose increase, new dose does not exceed 155 Units per treatment session. Approval duration: Medicaid/HIM – 24 weeks (two 12-week treatment sessions) Commercial – 6 months or to member’s renewal date, whichever is longer B. All Other Indications in Section I (must meet all):
    8. 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);
    9. Member is responding positively to therapy;
    10. Xeomin is not prescribed concurrently with other botulinum toxin products;
    11. Botulinum toxin therapy for cosmetic or medical conditions has not been administered within the last 12 week (16 weeks if sialorrhea);

55. If request is for a dose increase, new dose does not exceed the following indication- specific maximums (a, b, c, d, e, f, or g): a. Chronic sialorrhea (i or ii):
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    CLINICAL POLICY IncobotulinumtoxinA i. For age ≥ 18 years, dose does not exceed 30 Units per parotid gland, 20 Units per submandibular gland, 100 Units per treatment session; ii. For age ≥ 2 years, dose does not exceed any of the following (a, b, c, d, e, or f): a) For body weight 12 kg to < 15 kg, 6 Units per parotid gland, 4 Units per submandibular gland, 20 Units per treatment session; b) For body weight 15 kg to < 19 kg, 9 Units per parotid gland, 6 Units per submandibular gland, 30 Units per treatment session; c) For body weight 19 kg to < 23 kg, 12 Units per parotid gland, 8 Units per submandibular gland, 40 Units per treatment session; d) For body weight 23 kg to < 27 kg, 15 Units per parotid gland, 10 Units per submandibular gland, 50 Units per treatment session; e) For body weight 27 kg to < 30 kg, 18 Units per parotid gland, 12 Units per submandibular gland, 60 Units per treatment session; f) For body weight ≥ 30 kg, 22.5 Units per parotid gland, 15 Units per submandibular gland, 75 Units per treatment session. b. Upper/lower limb spasticity, UE dystonia, UE essential tremor: 400 Units per treatment session;
    c. OMD: 25 Units per treatment session; d. CD (i or ii):
    i. Treatment-naïve: 120 Units per treatment session; ii. Treatment-experienced: 300 Units per treatment session; e. Blepharospasm: 50 Units per eye per treatment session; f. OAB/urinary incontinence: 200 Units per treatment session; g. Axillary hyperhidrosis: 100 Units per treatment session. Approval duration: Medicaid/HIM – 16 weeks for sialorrhea (single treatment session), 12 weeks for all other indications (single treatment session) Commercial – 6 months or to member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2):

56. 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

57. 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 8 of 20

    CLINICAL POLICY IncobotulinumtoxinA 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 400 Units. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CD: cervical dystonia CGRP: calcitonin gene-related peptide FDA: Food and Drug Administration 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 See regimen information 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) benztropine mesylate (oral tablets - 0.5 mg, 1 mg, 2 mg) 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) See regimen information Page 9 of 20

    CLINICAL POLICY IncobotulinumtoxinA Drug Name Dosing Regimen 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 Dose Limit/ Maximum Dose • 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 once daily 25 mg orally once daily 50 mg/day Myrbetriq (mirabegron)
    (beta-3 agonist) Botox (OnabotulinumtoxinA) Dysport (abobotulinumtoxinA) OAB: Up to 5 Units IM per injection across up to 20 injection sites in the detrusor muscle for a total of up to 100 Units per treatment session Urinary incontinence associated with neurologic condition: Up to approximately 6.7 Units IM per injection across up to 30 injection sites in the detrusor muscle for a total of up to 200 Units per treatment session Up to 250 Units IM in the detrusor muscle per treatment session. (Off-label - Irwin 2013) See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks
    See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks
    Refer to prescribing information Chronic migraine Examples of oral migraine preventive therapies -
    • Anticonvulsants: divalproex (Depakote®), topiramate (Topamax®) Refer to prescribing information for dosing regimens. Page 10 of 20

    CLINICAL POLICY IncobotulinumtoxinA Drug Name Dosing Regimen Dose Limit/ Maximum Dose • Beta blockers: propranolol (Inderal®), metoprolol (Lopressor®), timolol
    • Antidepressants/tricyclic antidepressants: amitriptyline (Elavil®), venlafaxine (Effexor®) Botox (OnabotulinumtoxinA)
    Up to 5 Units IM per injection across up to 7 head/neck muscles for a total of up to 155 Units per treatment session See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks One application/day See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks
    See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks
    Dysport (abobotulinumtoxinA) Up to 250 Units IM per treatment session. (Off-label - Alipour 2016, Menezes 2007) Primary axillary hyperhidrosis Drysol® (aluminum chloride) Botox (OnabotulinumtoxinA) Apply topically once daily Up to 50 Units IM per axilla per treatment session Dysport (abobotulinumtoxinA) Up to 200 Units IM per treatment session. (Off-label - Clinical Pharmacology, Heckmann 2001) Page 11 of 20

    Dose Limit/ Maximum Dose 1,200 mg/day of levodopa 30 mg/day See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks CLINICAL POLICY IncobotulinumtoxinA Drug Name Dosing Regimen Dystonia carbidopa/levodopa (Sinemet®, Duopa®, Rytary®) trihexyphenidyl Upper and lower limb spasticity Botox (OnabotulinumtoxinA) 25 mg/100 mg PO QD, and increase by 1 tablet every 3 to 5 days. 30 mg PO QD Adult: Up to 50 Units IM per injection and up to 400 Units per treatment session Dysport (abobotulinumtoxinA) Pediatric: • Upper limb spasticity: Up to the lower of 6 Units/kg or 200 Units IM per treatment session • Lower limb spasticity: Up to the lower of 8 Units/kg or 300 Units IM per treatment session • Upper and lower limb spasticity: Up to the lower of 10 Units/kg or 340 Units IM per treatment session Adult: 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 Pediatric: Divided among affected muscles every 12 weeks: • Upper limb: Up to the lowr 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 IM or 1,000 Units IM Upper and lower limbs: Up to the lower of 30 Units IM or 1,000 Units IM staying within per limb guidelines Page 12 of 20

    CLINICAL POLICY IncobotulinumtoxinA Drug Name Dosing Regimen Cervical Dystonia Botox® (OnabotulinumtoxinA) Up to 50 Units IM per injection, 100 Units total in the sternocleidomastoid (SCM) muscle, and 300 Units per treatment session Dysport (abobotulinumtoxinA) Divided among affected muscles every 12 weeks: Up to 1,000 Units IM Blepharospasm Botox® (OnabotulinumtoxinA) • Botox naive: Up to 2.5 Units IM per muscle, 7.5 Units per eye, and 15 Units per treatment session • Botox experienced: Up to 5 Units IM per muscle, 15 Units per eye, and 30 Units per treatment session Dysport (abobotulinumtoxinA) Up to 120 Units SC per treatment session. (Off-label - Hallet 2009, Micromedex, Truong 2008) Dose Limit/ Maximum Dose See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks See dosing regimens for maximum dose Frequency: One treatment session every 12 weeks 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/Boxed Warnings • Contraindication(s):
    o Known hypersensitivity to the active substance botulinum neurotoxin type A or to any of the excipients o Infection at the proposed injection sites • Boxed warning(s): Distant spread of toxin effect Page 13 of 20

    CLINICAL POLICY IncobotulinumtoxinA Appendix D: Botulinum Toxin Product Interchangeability • Potency Units of Xeomin are not interchangeable with other botulinum toxin product preparations (e.g., Dysport®, Botox®, Myobloc®). 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* Essential tremor - UE Sialorrhea OAB/urinary incontinence 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) American Academy of Neurology (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) Esophageal achalasia HD and IAS achalasia Chronic anal fissure American College of Gastroenterology (2020) American Pediatric Surgical Association (2017) American College of Gastroenterology (2021) 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 Chronic sialorrhea Maximum Dose Adults: 100 Units/16 weeks Pediatrics: 75 Units/16 weeks Dosing Regimen • Adults: up to 30 Units IM per parotid gland, 20 Units IM per submandibular gland, and 100 Units IM per treatment session every 16 weeks. • Pediatrics (by body weight): o 12 kg to < 15 kg, 6 Units per parotid gland, 4 Units per submandibular gland, 20 Units per treatment session; o 15 kg to < 19 kg, 9 Units per parotid gland, 6 Units per submandibular gland, 30 Units per treatment session; Page 14 of 20

    CLINICAL POLICY IncobotulinumtoxinA Indication CD Blepharospasm Upper limb spasticity Off-label uses Adults: Lower limb spasticity Adults: OAB/urinary incontinence associated with neurologic condition Adults: chronic migraine Adults: axillary hyperhidrosis Adults: OMD UE dystonia UE essential tremor
    Dosing Regimen o 19 kg to < 23 kg, 12 Units per parotid gland, 8 Units per submandibular gland, 40 Units per treatment session; o 23 kg to < 27 kg, 15 Units per parotid gland, 10 Units per submandibular gland, 50 Units per treatment session; o 27 kg to < 30 kg, 18 Units per parotid gland, 12 Units per submandibular gland, 60 Units per treatment session; o ≥ 30 kg, 22.5 Units per parotid gland, 15 Units per submandibular gland, 75 Units per treatment session. Up to 120 Units IM per treatment session every 12 weeks for treatment-naïve patients. Up to 300 Units IM per treatment session every 12 weeks for treatment-experienced patients. Up to 50 Units IM per eye per treatment session every 12 weeks. Up to 400 Units IM per treatment session every 12 weeks. Up to 400 Units IM per treatment session every 12 weeks. (Off-label - Bensmail 2020, Santamato 2013) Up to 200 Units IM in the detrusor muscle per treatment session every 12 weeks. (Off-label - Asafu-Adjei 2020) Maximum Dose 300 Units/12 weeks 100 Units/12 weeks 400 Units/12 weeks 400 Units/12 weeks 200 Units/12 weeks Up to 155 Units IM per treatment session every 12 weeks. (Off-label - Salazar 2014, Ion 2018) Up to 100 Units IM per treatment session every 12 weeks. (Off-label - Dressler 2010, Rosell 2013) Up to 25 Units IM per treatment session every 12 weeks. (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 400 155 Units/12 weeks 100 Units/12 weeks 25 Units/12 weeks 400 Units/12 weeks Page 15 of 20

    CLINICAL POLICY IncobotulinumtoxinA Indication Dosing Regimen Units IM per treatment session every 12 weeks). Maximum Dose VI. Product Availability
    Vials: 50 Units, 100 Units, 200 Units VII.