Naldemedine (Symproic) Form

Naldemedine (Symproic®) is an opioid antagonist. Naldemedine functions as a peripherally- acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. FDA Approved Indication(s) Symproic is 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. 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 Symproic 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, b, and c): 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 both of the following (a and b):
   a. 0.2 mg per day; b. 1 tablet per day. Page 1 of 6

   CLINICAL POLICY Naldemedine Approval duration: 6 months
   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 both of the following (a and b):
      a. 0.2 mg per day;
      b. 1 tablet per day. Approval duration: 12 months
      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: Page 2 of 6

   CLINICAL POLICY Naldemedine 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 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 10 to 20 g (15 to 30 mL or 1 to 2 packets) PO QD; 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 50-300 mg/day PO given in single or divided doses lactulose polyethylene glycol 3350 (MiraLax®) docusate sodium (Colace®) Movantik® (naloxegol) 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 360 mg/day 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. Page 3 of 6

   CLINICAL POLICY Naldemedine Appendix C: Contraindications/Boxed Warnings • Contraindication(s): patients with known or suspected gastrointestinal obstruction or at increased risk of recurrent obstruction, patients with a history of a hypersensitivity reaction to naldemedine • Boxed warning(s): none reported V. Dosage and Administration
   Indication OIC Dosing Regimen 0.2 mg PO QD with or without food Maximum Dose 0.2 mg /day VI. Product Availability
   Tablet: 0.2 mg VII.