PROBUPHINE IMPLANT KIT, Buprenorphine HCl SUBLOCADE, Buprenorphine PROBUPHINE IMPLANT KIT, Buprenorphine HCl SUBLOCADE, Buprenorphine Form

Buprenorphine (Sublocade®, Brixadi®) is a partial opioid agonist.
FDA Approved Indication(s) Sublocade is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a buprenorphine adjustment for a minimum of 7 days. containing product, followed by dose ‐ Brixadi is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of transmucosal buprenorphine product or who are already being treated with buprenorphine.
Sublocade and Brixadi should be used as part of a complete treatment program that includes counseling and psychosocial support. _ Sublocade and Brixadi are administered only by healthcare providers in a healthcare setting
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 Sublocade and Brixadi 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. Age ≥ 18 years;

3. Member meets one of the following (a, b, or c):
   a. Member is switching from another non-transmucosal buprenorphine-containing product (e.g., Sublocade, Brixadi); b. For Sublocade requests, member is currently on a transmucosal buprenorphine- containing product, delivering the equivalent of 8 mg to 24 mg of buprenorphine daily, for 7 days or longer; c. For Brixadi requests, member meets one of the following (i or ii):
   i. Has tolerated a single 4 mg dose of transmucosal buprenorphine-containing product; Page 1 of 10

   CLINICAL POLICY Buprenorphine Injection ii. Currently is being treated with a transmucosal buprenorphine-containing product;

   4. Medical justification supports inability to continue to use transmucosal (e.g., sublingual, buccal) formulations of buprenorphine as evidenced by one of the following (a, b, c, or d): a. Documentation of non-compliance to transmucosal formulations of buprenorphine;
      b. Treatment failure with transmucosal formulations of buprenorphine;
      c. History of diversion with buprenorphine medication-assisted treatment (MAT) products;
      d. Contraindication(s) or clinically significant adverse effects to the excipients of transmucosal formulations of buprenorphine;
   5. Dose does not exceed any of the following (a or b):
      a. Sublocade: 300 mg per month;
      b. Brixadi (i or ii):
      i. 32 mg per week;
      ii. 128 mg every 28 days.
      Approval duration:
      Medicaid/Commercial – 6 months (12 months for New Hampshire) HIM – 12 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 Dependence (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; Page 2 of 10

   CLINICAL POLICY Buprenorphine Injection 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 any of the following (a or b): a. Sublocade: 300 mg per month;
      b. Brixadi (i or ii):
      i. 32 mg per week;
      ii. 128 mg every 28 days. Approval duration: Medicaid/Commercial – 6 months (12 months for New Hampshire) HIM – 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. 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 MAT: medication-assisted treatment REMS: Risk Evaluation and Mitigation Strategy Page 3 of 10

   CLINICAL POLICY Buprenorphine Injection 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.
   Drug Name Dosing Regimen buprenorphine (Subutex) sublingual (SL) tablet buprenorphine/ naloxone (Suboxone) SL or buccal dissolving film, SL tablet Bunavail® (buprenorphine/ naloxone) buccal film Zubsolv® (buprenorphine/ naloxone) SL tablet Maintenance: Target dose: 16 mg PO once daily; dosage should be adjusted in increments or decrements of 2 mg or 4 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: 4 mg to 24 mg per day Maintenance: Target dose: buprenorphine 16 mg/naloxone 4 mg PO 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 Maintenance: Target dose: buprenorphine 8.4 mg/naloxone 1.4 mg PO once daily; dosage should be adjusted in increments or decrements of 2.1 mg/ 0.3 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: 2.1 mg/0.3 mg to 12.6 mg/2.1 mg per day Maintenance: Target dose: buprenorphine 11.4 mg/naloxone 2.9 mg PO 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 Dose Limit/ Maximum Dose 24 mg per day 24 mg/6 mg per day 12.6 mg/2.1 mg per day 17.2 mg/4.2 mg per 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): hypersensitivity to buprenorphine or any other ingredients in Sublocade or Brixadi • Boxed warning(s): risk of serious harm or death with intravenous administration; available only through a restricted program called the Sublocade or Brixadi REMS Program Page 4 of 10

   CLINICAL POLICY Buprenorphine Injection Appendix D: Brand/Generic Transmucosal Formulations Equivalent to Subutex or Suboxone Sublingual Tablets Containing ≤ 8 mg of Buprenorphine Drug Transmucosal Formulation Brand/ Generic† Tablet, sublingual Tablet, sublingual buprenorphine HCL buprenorphine HCL/ naloxone HCL Generic Generic Zubsolv Film, buccal
   Bunavail Film, sublingual or buccal Suboxone Brand/ Generic Strength Subutex/Suboxone‡ Sublingual Tablet Strength Buprenorphine/Naloxone§ Equivalency 2 mg 8 mg 2 mg/0.5 mg 8 mg/2 mg 1.4 mg/0.36 mg 2.9 mg/0.71 mg 5.7 mg/1.4 mg 2.1 mg/0.3 mg 4.2 mg/0.7 mg 2 mg/0.5 mg 4 mg/1 mg 8 mg/2 mg 2 mg (Subutex) 8 mg (Subutex) 2 mg/0.5 mg (Suboxone) 8 mg/2 mg (Suboxone) 2 mg/0.5mg (Suboxone) 4 mg/1 mg (Suboxone) 8 mg/2 mg (Suboxone) 4 mg/1 mg (Suboxone) 8 mg/2 mg (Suboxone) 2 mg/0.5 mg (Suboxone) 4 mg/1 mg (Suboxone) 8 mg/2 mg (Suboxone) Transmucosal formulations include buprenorphine and buprenorphine/naloxone sublingual tablets and buccal/sublingual films. †For a more comprehensive listing of brand/generic sublingual/buccal transmucosal formulations see the U.S. Food & Drug Administration Orange Book: Approved drug products with therapeutic equivalence evaluations at http://www.accessdata.fda.gov/scripts/cder/ob/search_product.cfm. ‡Subutex (buprenorphine) and Suboxone (buprenorphine/naloxone) sublingual tablets, while used as buprenorphine equivalency references, are no longer available in the U.S. §Naloxone (an opioid antagonist) is minimally absorbed in sublingual/buccal transmucosal formulations and rather is added to discourage diversion or misuse. V. Dosage and Administration
   Drug Name Buprenorphine (Sublocade) Dosing Regimen Two monthly initial doses of 300 mg subcutaneously followed by 100 mg monthly maintenance doses Maximum Dose 300 mg per month Buprenorphine (Brixadi) Increasing the maintenance to 300 mg monthly may be considered for patients in which the benefits outweigh the risks Patients not currently receiving buprenorphine treatment • The recommended weekly dose is 24 mg subcutaneously weekly titrated over the first week. If needed, during this week of treatment, administer an additional 8 mg dose of Brixadi (weekly), waiting at least 24 hours after the previous injection, for a total weekly dose of 32 mg.
   32 mg per week or 128 mg per 28 days Page 5 of 10

   CLINICAL POLICY Buprenorphine Injection Drug Name Maximum Dose Dosing Regimen • Administer subsequent weekly injections based on the total weekly dose that was established in week one. Dose adjustments can be made at weekly appointments with the maximum weekly dose being 32 mg.
   Patients switching from transmucosal buprenorphine-containing products
   Patients currently treated with a transmucosal buprenorphine-containing product may be switched directly to either weekly or monthly Brixadi. Refer to Prescribing Information for suggested corresponding weekly or monthly Brixadi.
   Patients transitioning between weekly and monthly Brixadi
   Refer to Prescribing Information for recommended dose when transitioning between weekly and monthly Brixadi. Dose adjustments of Brixadi
   An additional 8 mg of Brixadi (weekly) may be administered, based on clinical judgement during a dosing interval, up to a maximum dose of 32 mg per week or 128 mg per month.
   Other Brixadi (weekly) should be administered in 7- day intervals. Brixadi (monthly) should be administered in 28-day intervals. Weekly doses of Brixadi cannot be combined to yield a monthly dose. Administer Brixadi as a single injection, and do not divide VI. Product Availability
   Drug Name Buprenorphine (Sublocade) Buprenorphine (Brixadi)
   Availability Prefilled syringes: 100 mg/0.5 mL and 300 mg/1.5 mL • Prefilled single-dose syringes – weekly: 8 mg/0.16 mL, 16 mg/0.32 mL, 24 mg/0.48 mL, and 32 mg/0.64 mL • Prefilled single-dose syringes – monthly: 64 mg/0.18 mL, 96 mg/0.27 mL, and 128 mg/0.36 mL Page 6 of 10

   CLINICAL POLICY Buprenorphine Injection VII.