SUBOXONE, Buprenorphine HCl-Naloxone HCl Dihydrate BUNAVAIL, Buprenorphine HCl-Naloxone HCl Dihydrate Form

Buprenorphine/naloxone (Suboxone® and Zubsolv®) is a partial opioid agonist. FDA Approved Indication(s) Suboxone and Zubsolv are indicated for the treatment of opioid dependence.
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 Suboxone and Zubsolv are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Opioid Dependence (must meet all):

1. Diagnosis of opioid dependence;
2. Member must use generic buprenorphine/naloxone sublingual tablets or film;

3. Dose does not exceed:
   a. Suboxone: 24 mg/6 mg per day; b. Zubsolv: 17.2 mg/4.2 mg per day. Approval duration: 12 months
   B. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   2. 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 1 of 7

   CLINICAL POLICY Buprenorphine-Naloxone 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 Dependence (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);
4. Member is responding positively to therapy;

5. One of the following conditions is met (a or b):
   a. Member has NOT received an opioid analgesic since last approval; b. Prescriber submits documentation acknowledging that the use of opioid during the last approval period was due to a diagnosis of acute pain;

   4. If request is for a dose increase, new dose does not exceed: a. Suboxone: 24 mg/6 mg per day; b. Zubsolv: 17.2 mg/4.2 mg per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
   5. 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
   6. 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. Pain management; B. 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 policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, CP.PMN.53 for Medicaid, or evidence of coverage documents.
      Page 2 of 7

   CLINICAL POLICY Buprenorphine-Naloxone IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration SL: sublingual
   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 24 mg/6 mg per day 24 mg/6 mg per day buprenorphine/ naloxone sublingual (SL) tablets buprenorphine/ naloxone SL film Maintenance: Target dose: buprenorphine 16 mg/naloxone 4 mg SL once daily; dosage should be adjusted in increments or decrements of 2 mg/ 0.5 mg or 4 mg/1 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: 4 mg/1 mg to 24 mg/6 mg per day • DAY 1 DOSING: First induction dose buprenorphine; naloxone 2 mg/0.5 mg or 4 mg/1 mg SL film; may titrate in 2 or 4 mg increments of buprenorphine, at approximately 2-hour increments, under supervision, up to a total dose of buprenorphine/naloxone 8 mg/2 mg SL film.
   • DAY 2 DOSING: A single daily dose of buprenorphine; naloxone up to 16 mg/4 mg SL film is recommended.
   • DAY 3 DOSING AND BEYOND: Progressively adjust dose in increments or decrements of 2 mg/0.5 mg or 4 mg/1 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. 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): hypersensitivity to buprenorphine or naloxone • Boxed warning(s): none reported V. Dosage and Administration
   Drug Name buprenorphine/ naloxone (Suboxone) Dosing Regimen Induction: Titrate to 8 mg/2 mg SL on Day 1 and 16 mg/4 mg SL on Day 2; then start Maximum Dose 24 mg/6 mg per day Page 3 of 7

   CLINICAL POLICY Buprenorphine-Naloxone Drug Name SL or buccal dissolving film buprenorphine/ naloxone (Zubsolv) SL tablet Maximum Dose 17.2 mg/4.2 mg per day Dosing Regimen maintenance treatment Maintenance: Target dose: buprenorphine 16 mg/naloxone 4 mg once daily; dosage should be adjusted in increments or decrements of 2 mg/0.5 mg or 4 mg/1 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: 4 mg/1 mg to 24 mg/6 mg per day Induction: Titrate to 5.7 mg/1.4 mg SL on Day 1 and 11.4 mg/2.9 mg SL on Day 2; then start maintenance treatment
   Maintenance: Target dose: buprenorphine 11.4 mg/naloxone 2.9 mg once daily; dosage should be adjusted in increments or decrements of 2.9 mg/ 0.71 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: 2.9 mg/0.71 mg to 17.2 mg/4.2 mg per day VI. Product Availability
   Drug Name buprenorphine/naloxone (Suboxone) buprenorphine/naloxone (Zubsolv) Availability Sublingual film: buprenorphine/naloxone 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, 12 mg/3 mg Sublingual tablet: buprenorphine/naloxone 0.7 mg/0.18 mg, 1.4 mg/0.36 mg, 2.9 mg /0.71 mg, 5.7 mg/1.4 mg, 8.6 mg/2.1 mg, 11.4 mg/2.9 mg VII.