CONTRAVE, Naltrexone HCl-Bupropion HCl Form

Bupropion/naltrexone (Contrave®) is a combination of naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant. FDA Approved Indication(s) Contrave is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of:
• 30 kg/m2 or greater (obese), or
• 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia. Limitation(s) of use:
• The effect of Contrave on cardiovascular morbidity and mortality has not been established. • The safety and effectiveness of Contrave in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established. 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 Contrave is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Weight Management (must meet all):

1. Member meets one of the following (a or b):
   a. BMI ≥ 30 kg/m2; b. BMI ≥ 27 kg/m2 with at least one indicator of increased cardiovascular risk (e.g., coronary artery/heart disease, hypertension, dyslipidemia, diabetes, elevated waist circumference) or other obesity-related medical condition (e.g., sleep apnea);
2. Age ≥ 18 years;
   3. Documentation that member is actively enrolled in a weight loss program that involves a reduced calorie diet and increased physical activity adjunct to therapy;

3. Contrave is not prescribed concurrently with bupropion containing products;

   5. Dose does not exceed 32 mg naltrexone/360 mg bupropion per day (4 tablets per day). Page 1 of 6

   CLINICAL POLICY Bupropion/Naltrexone Approval duration: 12 weeks B. Other diagnoses/indications (must meet 1 or 2):

4. 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or
5. 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 and HIM.PA.154 for health insurance marketplace.
   II. Continued Therapy A. Weight Management (must meet all):
6. 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);
7. Member is responding positively to therapy as evidenced by one of the following (a or b):
   a. If this is the first renewal request, member has lost ≥ 5% of baseline body weight; b. If this is a second or subsequent renewal request, member has lost weight and/or maintained weight loss on therapy;
8. Documentation that member is actively enrolled in a weight loss program that involves a reduced calorie diet and increased physical activity adjunct to therapy;
9. Contrave is not prescribed concurrently with bupropion containing products;
   5. If request is for a dose increase, new dose does not exceed 32 mg naltrexone/360 mg bupropion per day (4 tablets per day). Approval duration:
      First reauthorization – 12 weeks Subsequent reauthorizations – 6 months B. Other diagnoses/indications (must meet 1 or 2):

10. 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): Page 2 of 6

    CLINICAL POLICY Bupropion/Naltrexone 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or

11. 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 and HIM.PA.154 for health insurance marketplace.
    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 and HIM.PA.154 for health insurance marketplace or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BMI: body mass index FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed warnings • Contraindication(s): uncontrolled hypertension, seizure disorder, concomitant use or use within 14 days of a monoamine oxidase inhibitor, chronic opioid use, use of other bupropion-containing products, bulimia or anorexia nervosa, abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, and hypersensitivity to any of the ingredients in Contrave • Boxed warning(s): increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Monitor for worsening and emergence of suicidal thoughts and behaviors. Contrave has not been studied in pediatric patients Appendix D: General Information
    • BMI = 703 x [weight (lbs)/height (inches)2] • Examples of coronary artery/heart disease include: coronary artery bypass graft, angina, history of myocardial infarction or stroke. • Per Contrave’s prescribing information, response to therapy should be evaluated after 12 weeks at the maintenance dosage. If a patient has not lost at least 5% of baseline body weight, Contrave should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. This is in line with Page 3 of 6

    CLINICAL POLICY Bupropion/Naltrexone the Endocrine Society’s definition of an effective response to a weight loss medication (2015).
    V. Dosage and Administration Indication Weight management Dosing Regimen Week 1: One tablet PO QAM Week 2: One tablet PO BID Week 3: Two tablets PO QAM and 1 tablet PO QPM Week 4 and onward: 2 tablets PO BID Maximum Dose 32/360 mg per day VI. Product Availability Extended-release tablet: 8 mg naltrexone/90 mg bupropion VII.