# Clinical Policy: IncobotulinumtoxinA (Xeomin)
Reference Number: CP.PHAR.231  
Effective Date: 07.01.16  
Last Review Date: 05.26  
Line of Business: Commercial, HIM/ICHRA, Medicaid  

[Coding Implications](Coding Implications)  
[Revision Log](Revision Log)  

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.  

## Description  
IncobotulinumtoxinA (Xeomin®) is an acetylcholine release inhibitor and a neuromuscular blocking agent.  

### FDA Approved Indication(s)  
| Indication | Adults | Pediatrics | Treatment | Prophylaxis |  
|------------|--------|------------|-----------|-------------|  
| Sialorrhea | X | X | X |  |  
| Upper limb spasticity | X | X | X |  |  
| Cervical dystonia (focal dystonia) | X |  | X |  |  
| Blepharospasm (focal dystonia) | X |  | X |  |  
| Upper facial lines [benefit exclusion] | X |  | X |  |  

### Off-Label Uses  
| Indication | Adults | Pediatrics | Treatment | Prophylaxis |  
|------------|--------|------------|-----------|-------------|  
| Lower limb spasticity\* | X |  | X |  |  
| Overactive bladder | X |  | X |  |  
| Urinary incontinence | X |  | X |  |  
| Migraine | X |  | X | X |  
| Axillary hyperhidrosis | X |  | X |  |  
| Laryngeal dystonia\*\* | X |  | X |  |  
| Oromandibular dystonia\*\* | X |  | X |  |  
| Upper extremity dystonia\*\* | X |  | X |  |  
| Upper extremity essential tremor\*\*\* | X |  | X |  |  

\*See criteria set entitled Upper and Lower Limb Spasticity  
\*\*See criteria set entitled Focal Dystonia and Essential Tremor  

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  
- The appearance of upper facial lines [benefit exclusion]:  
  - Moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity  
  - Moderate to severe horizontal forehead lines associated with frontalis muscle activity  
  - Moderate to severe lateral canthal lines associated with orbicularis oculi muscle activity  


# CLINICAL POLICY  
IncobotulinumtoxinA  

  
8. 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;  
      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/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
8. Dose does not exceed 400 Units per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
10. 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/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
9. Dose does not exceed 50 Units per eye per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
9. Dose does not exceed 200 Units per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
10. Dose does not exceed 155 Units per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
9. Dose does not exceed 100 Units per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
9. Request meets one of the following (a or b):  
   a. Laryngeal dystonia: Dose does not exceed 25 Units per treatment session;  
   b. UE essential tremor, OMD: 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/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  

### II. Continued Approval  
  
7. If request is for a dose increase, new dose does not exceed 155 Units per treatment session.  

**Approval duration:**  
Medicaid/HIM/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  
   a. Chronic sialorrhea (i or ii):  
      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. Focal dystonia and essential tremor (i and ii):  
      i. Laryngeal dystonia: 25 Units per treatment session;  
      ii. UE dystonia, UE essential tremor, OMD: 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);  
   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/ICHRA – 12 months  
Commercial – 6 months or to member’s renewal date, whichever is longer  

  

### III.Diagnoses/Indications for which coverage is NOT authorized:  
#### A. Non-FDA documented 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/ICHRA, 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  
#### Appendix A: Abbreviation/Acronym Key  
CD: cervical dystonia  
CGRP: calcitonin gene-related peptide  
ER: extended release  
FDA: Food and Drug Administration  
IR: immediate release  
MS: multiple sclerosis  

OAB: overactive bladder  
SCI: spinal cord injury  
UE: upper extremity  
OMD: oromandibular dystonia  

#### 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 |  
|-----------|---------------|------------------------|  
| **Sialorrhea: examples of anticholinergic drugs** | | |  
| glycopyrrolate (Glycate® oral tablets, Cuvposa® oral solution) | • Adults: 1 mg PO TID (Off-label: Lakraj 2013) <br> • 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. <br> (FDA labeled) | See regimen information |  
| 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 

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CLINICAL POLICY

IncobotulinumtoxinA

Chronic migraine

| Examples of oral migraine preventive therapies–<br>• Anticonvulsants:<br>• divalproex (Depakote®),<br>• topiramate (Topamax®) | Refer to prescribing information for dosing regimens. | Refer to prescribing information |

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IncobotulinumtoxinA

Primary axillary hyperhidrosis

| Drysol® (aluminum chloride) | Apply topically once daily | One application/day |

| Botox (OnabotulinumtoxinA) | Up to 50 Units IM per axilla per treatment session | See dosing regimens for maximum dose<br><br>Frequency:<br>One treatment session every 12 weeks |

| Dysport (abobotulinumtoxinA) | Up to 200 Units IM per treatment session.<br>(Off-label– Clinical Pharmacology, Heckmann 2001) | See dosing regimens for maximum dose<br><br>Frequency:<br>One treatment session every 12 weeks |

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CLINICAL POLICY

IncobotulinumtoxinA

Dystonia

Upper and lower limb spasticity

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IncobotulinumtoxinA

Cervical Dystonia

Blepharospasm

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):
○ Known hypersensitivity to the active substance botulinum neurotoxin type A or to any of the excipients
○ Infection at the proposed injection sites
• Boxed warning(s): Distant spread of toxin effect

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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

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

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IncobotulinumtoxinA

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IncobotulinumtoxinA

VI. Product Availability
Vials: 50 Units, 100 Units, 200 Units

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Coding Implications
Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

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IncobotulinumtoxinA

Important Reminder
This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

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**CLINICAL POLICY**
IncobotulinumtoxinA

**Note:**
**For Medicaid members, when state Medicaid coverage provisions conflict with the coverage
provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please
refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.**

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