RELISTOR, Methylnaltrexone Bromide Form

Methylnaltrexone bromide (Relistor®) is an opioid antagonist.
FDA Approved Indication(s) Relistor tablets and injection are indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Relistor injection is indicated for the treatment of OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care. 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.
It is the policy of health plans affiliated with Centene Corporation® that Relistor is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Opioid Induced Constipation (must meet all):

1. Diagnosis of OIC;
   2. Age ≥ 18 years;
   3. Member has been taking opioid(s) for ≥ 4 weeks due to chronic pain not caused by active cancer;
2. Failure of one agent from each of the following classes while on opioid therapy, unless clinically significant adverse effects are experienced or all are contraindicated: a. Stimulant laxative (e.g., bisacodyl, senna); b. Osmotic laxative (e.g., lactulose, polyethylene glycol); c. Stool softener (e.g., docusate);
3. Member has used one of the aforementioned agents in the past 30 days, unless contraindicated;
4. Failure of Movantik®, unless contraindicated or clinically significant adverse effects are experienced;
   *Prior authorization may be required for Movantik

5. Dose does not exceed the following one of the following (a or b): a. For tablets, both of the following (i and ii):
   i. 450 mg per day;
   Page 1 of 7

   CLINICAL POLICY Methylnaltrexone bromide ii. 3 tablets per day; b. Injection: FDA-approved weight-based dosing (see Section V). Approval duration:
   Medicaid/HIM – 6 months
   Commercial – Tablets: 6 months; Injection: 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

6. 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

7. 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 Therapy A. Opioid Induced Constipation (must meet all):

   1. 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 continues to receive opioid therapy;
   3. Member is responding positively to therapy;
   4. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. For tablets, both of the following (i and ii):
      i. 450 mg per day;
      ii. 3 tablets per day; b. Injection: FDA-approved weight-based dosing (see Section V).
      Approval duration:
      Medicaid/HIM – 12 months
      Commercial – Tablets: 6 months; Injection: 6 months or to the member’s renewal date, whichever is longer Page 2 of 7

   CLINICAL POLICY Methylnaltrexone bromide B. Other diagnoses/indications (must meet 1 or 2):

8. 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

9. 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.
   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.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration OIC: opioid induced constipation 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.
   Dosing Regimen Drug Name Dose Limit/ Maximum Dose 15 mg/day PO; 10 mg/day rectally 68.8 mg sennosides/day (8 tablets/day) 40 g/day (60 mL or 2 to 4 packets/day) 34 g/day bisacodyl (Dulcolax®) senna (Senokot®) Oral: 5 to 15 mg QD Rectal: Enema, suppository: 10 mg (1 enema or suppository) QD 1 to 2 tablets (8.6 to 17.2 mg sennosides) PO BID lactulose polyethylene glycol 3350 (MiraLax®) 10 to 20 g (15 to 30 mL or 1 to 2 packets) daily; may increase to 40 g (60 mL or 2 to 4 packets) PO QD if necessary 17 g (approximately 1 heaping tablespoon) of powder in 120 to 240 mL of fluid given PO QD Page 3 of 7

   CLINICAL POLICY Methylnaltrexone bromide Drug Name Dosing Regimen docusate sodium (Colace®) 50-300 mg/day PO given in single or divided doses Dose Limit/ Maximum Dose 360 mg/day Movantik® (naloxegol) 25 mg PO QD, if not tolerated, reduce to 12.5 mg PO QD 25 mg/day 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): patients with known or suspected mechanical gastrointestinal obstruction and at increased risk of recurrent obstruction
   • Boxed warning(s): none reported Appendix D: General Information
   • Advanced illness is defined as life-ending or terminal disease. In Relistor clinical trials, opioid induced constipation was defined as less than three bowel movements in the preceding week or no bowel movement for 2 days. • The use of Relistor beyond four months has not been studied. V. Dosage and Administration
   Indication OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dose escalation for palliative care OIC in adult patients with chronic non- cancer pain Dosing Regimen The recommended dosage regimen is one dose administered SC QOD, as needed. Do not administer more frequently than one dose per 24- hour period. Maximum Dose Refer to dosing regimen Weight-Based Dosing of Relistor Injection Weight of Adult Patient Subcutaneous Dose and Corresponding Injection Volume 0.15 mg/kg 8 mg = 0.4 mL 12 mg = 0.6 mL 0.15 mg/kg Less than 38 kg 38 kg to less than 62 kg 62 kg to 114 kg More than 114 kg *Calculate the injection volume for these patients by multiplying the patient weight in kilograms by 0.0075 and then rounding up the volume to the nearest 0.1 mL. 12 mg SC QD or 450 mg PO QD 12 mg/day SC 450 mg/day PO VI. Product Availability
   • Tablets: 150 mg Page 4 of 7

   CLINICAL POLICY Methylnaltrexone bromide • Injection: o 8 mg/0.4 mL methylnaltrexone bromide in a single-dose pre-filled syringe o 12 mg/0.6 mL methylnaltrexone bromide in a single-dose pre-filled syringe, or single-dose vial VII.