Olanzapine/Samidorphan (Lybalvi) Form

Olanzapine/samidorphan (Lybalvi™) is combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist. FDA Approved Indication(s) Lybalvi is indicated for the treatment of: • Schizophrenia in adults • Bipolar I disorder in adults o Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate o Maintenance monotherapy treatment 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 Lybalvi is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Bipolar Disorder and Schizophrenia (must meet all):

1. Diagnosis of bipolar disorder or schizophrenia;
2. Age ≥ 18 years;

3. Member meets one of the following (a, b, or c):
   a. Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D); b. Member must use olanzapine at up to maximally indicated doses, unless contraindicated to excipients, clinically significant adverse effects are experienced; c. Member has diabetes mellitus or body mass index (BMI) > 30 kg/m2;

   4. Member meets one of the following (a or b):
      a. Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D); b. Failure of a 4-week trial of one additional preferred atypical antipsychotic (e.g., aripiprazole, ziprasidone, quetiapine, risperidone) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated; Page 1 of 7

   CLINICAL POLICY Olazanpine/Samidorphan

   5. Dose does not exceed 20 mg olanzapine/10 mg samidorphan (1 tablet) per day. Approval duration: 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. Bipolar Disorder and Schizophrenia (must meet all):
   8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Lybalvi for bipolar disorder or schizophrenia and has received this medication for at least 30 days;
4. Member is responding positively to therapy;

5. If request is for a dose increase, new dose does not exceed 20 mg olanzapine/10 mg samidorphan (1 tablet) 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 2 of 7

   CLINICAL POLICY Olazanpine/Samidorphan 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.
   B. Dementia-related psychosis.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BMI: body mass index FDA: Food and Drug Administration 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 30 mg/day 20 mg/day 800 mg/day Schizophrenia: 16 mg/day Bipolar Disorder: 6 mg/day 160 mg/day aripiprazole (Abilify®) olanzapine (Zyprexa®) Bipolar Disorder and Schizophrenia Adults: 10 to 15 mg PO QD Schizophrenia Initial: 5 to 10 mg PO QD; target: 10 mg PO QD quetiapine (Seroquel®) risperidone (Risperdal®) Bipolar Disorder Monotherapy: 10 to 15 mg PO QD; adjunct to lithium or valproate: 10 mg PO QD
   Schizophrenia Initial: 25 mg PO BID; target: 400 to 800 mg/day Bipolar Disorder Initial: 50 mg PO BID; target: 400 to 800 mg/day Schizophrenia Initial: 1 mg PO BID or 2 mg PO QD; target: 4 to 8 mg PO QD ziprasidone (Geodon®) Bipolar Disorder 2 to 3 mg PO QD Schizophrenia 20 mg PO BID Bipolar Disorder Initial: 40 mg PO BID; target: 40 to 80 mg PO BID Page 3 of 7

   CLINICAL POLICY Olazanpine/Samidorphan 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 using opioids; patients undergoing acute opioid withdrawal; if Lybalvi is administered with lithium or valproate, refer to the lithium or valproate prescribing information for the contraindications for those products • Boxed warning(s): increased mortality in elderly patients with dementia-related psychosis Appendix D: States with Limitations against Redirections in Certain Mental Health Settings State Step Therapy Prohibited? Yes Notes AR NV No TX No Applies to HIM requests only For the treatment of psychosis and serious mental illness through antipsychotic prescription drugs, no step therapies allowed. Applies to Medicaid requests only Failure of a 4-week trial of olanzapine or one preferred atypical antipsychotic (e.g., aripiprazole, ziprasidone, quetiapine, risperidone) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated. Applies to HIM requests only Failure of a 4-week trial of olanzapine or one preferred atypical antipsychotic (e.g., aripiprazole, ziprasidone, quetiapine, risperidone) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated. V. Dosage and Administration
   Indication Schizophrenia Bipolar I disorder Dosing Regimen Initiate at 5 mg/10 mg or 10 mg/10 mg PO QD. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg. Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component) depending upon clinical response and tolerability. Monotherapy: Initiate at 10 mg/10 mg or 15 mg/10 mg PO QD. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg PO QD. Dosage adjustments should occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments/decrements of 5 mg (based on the olanzapine component) are recommended.
   Maximum Dose 20 mg/10 mg/day 20 mg/10 mg/day Page 4 of 7

   CLINICAL POLICY Olazanpine/Samidorphan Indication Dosing Regimen Maintenance monotherapy: Administer at 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg PO QD.
   Maximum Dose Adjunctive to lithium or valproate: Initiate at 10 mg/10 mg PO QD. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg or 20 mg/10 mg PO QD. Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component), depending upon clinical response and tolerability. VI. Product Availability
   Tablets (olanzapine/samidorphan): 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, 20 mg/10 mg VII.