ModifiedHealth NetPolicy N/A

Clinical Policy: Olanzapine/Samidorphan (Lybalvi)

Defines medical necessity, prior authorization, step therapy, dosing limits, and exclusions for Lybalvi (olanzapine/samidorphan) for commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerHealth Net

PolicyOlanzapine/Samidorphan (Lybalvi) clinical coverage criteria

Policy CodePolicy N/A

Change TypeMaterial amendments to step therapy and exclusions

Effective DateSep 1, 2021

Next Review DateN/A

Key ActionSubmit prior authorization with diagnosis, age ≥18, required documentation, evidence of prior therapy or applicable state bypass, and dosing within 20 mg/10 mg per day.

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for Illinois HIM requests per IL HB 5395 effective 1/1/2026.

Added Appendix D listing states with limitations on redirections in certain mental health settings (including AR, NV, TX, IL additions noted).

Added dementia-related psychosis to the list of diagnoses for which coverage is not authorized.

Added step therapy bypass for Illinois Health Insurance Marketplace (HIM) per IL HB 5395.

Added redirection bypass for members in states with limitations on step therapy and updated Appendix D to include Arkansas, Texas, and Nevada with specific redirection requirements.

Annual reviews through 2025 noted; references reviewed and updated with no significant changes to clinical policy content.

20 mg/10 mgMaximum daily dose

12 months

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

Initial Therapy

Covered when ALL of the following are met for initial therapy:

Initial Approval - Bipolar Disorder and Schizophrenia: 1) Diagnosis of bipolar disorder or schizophrenia; 2) Age ≥ 18 years; 3) Member meets ONE of: (a) request is for treatment of a member in a state with limitations on therapy in certain mental health settings (see Appendix D) allowing bypass, OR (b) member has diabetes mellitus or body mass index (BMI) > 30 kg/m^2, OR (c) 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 contraindicated or clinically significant adverse effects were experienced; 4) Dose does not exceed 20 mg olanzapine/10 mg samidorphan per day.dose <=20/10

Approval duration: 12 months

Continuation Therapy

Covered when ALL of the following are met for continued therapy:

Continued Therapy - Bipolar Disorder and Schizophrenia: 1) Member is currently receiving medication via the Centene benefit or documentation supports that the member has been receiving Lybalvi for at least 30 days; 2) Member is responding positively to therapy; 3) If a dose increase is requested, the new dose does not exceed 20 mg olanzapine/10 mg samidorphan per day.dose <=20/10

Approval duration: 12 months

Diagnoses or indications not addressed in this policy are not authorized unless supported by documentation consistent with applicable off‑label use policies or evidence of coverage. Dementia‑related psychosis is explicitly listed as a diagnosis for which coverage is NOT authorized, consistent with the product boxed warning regarding increased mortality in elderly patients with dementia‑related psychosis.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers should consult the applicable state Medicaid manual and the member's coverage documents for any state‑specific requirements.

Use of Lybalvi for dementia‑related psychosis is not authorized due to the increased mortality observed in elderly patients with dementia‑related psychosis, as noted in the boxed warning. Requests for this indication will not meet coverage criteria.

Coding and Dosing

Product availability (NDCs/details not provided)NDC

NDCs not listed

Product availability: tablets 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, 20 mg/10 mg

inv-07: Maximum daily dose — 20 mg olanzapine / 10 mg samidorphan per day

Maximum daily dose (combined)20 mg olanzapine / 10 mg samidorphan per day

Per-tablet dosingEach tablet equals 10 mg samidorphan with olanzapine strengths of 5, 10, 15, or 20 mg (product available as 5/10, 10/10, 15/10, 20/10 mg)

Approval duration tied to dosingApproval duration listed as 12 months when dosing does not exceed 20 mg/10 mg per day

Provider Actions and Prior Authorization

Documentation Required

Documentation Required and Indication‑Related Denials

Prior authorization is required. Provider must submit documentation (such as chart notes, lab results or other clinical information) supporting that the member has met all approval criteria. Requests that lack required documentation or are for excluded indications (for example, dementia-related psychosis or other non‑FDA approved uses without sufficient supporting evidence) may be denied.

Required documentation: chart notes, labs, other clinical information supporting criteria met
Excluded indications: dementia-related psychosis; non‑FDA approved indications without sufficient documentation per applicable off‑label policies

Denial Risk

Denial Risk from Contractual or Regulatory Non‑Compliance

Coverage decisions are subject to the member's contract terms, Evidence of Coverage, state and federal requirements, and Health Plan administrative policies. Failure to comply with contractual or regulatory requirements (including state Medicaid rules when applicable) may result in denial of the request.

Background

Lybalvi is a fixed‑dose combination of olanzapine (an atypical antipsychotic) and samidorphan (an opioid antagonist) approved for the treatment of schizophrenia and bipolar I disorder in adults. Samidorphan is included to mitigate olanzapine‑associated weight gain through opioid receptor antagonism. Prescribing information includes dosing options (tablets containing olanzapine/samidorphan in several strengths) and contraindications; in particular, Lybalvi is contraindicated in patients using opioids or undergoing acute opioid withdrawal, and clinicians should consult lithium and valproate prescribing information if co‑administration is considered.

Definitions

inv-17: Olanzapine/samidorphan combination product — Lybalvi key definition

Product name (term)Lybalvi (olanzapine/samidorphan combination product)

ComponentsOlanzapine (atypical antipsychotic) + samidorphan (opioid antagonist)

Indications (documented)Approved for treatment of schizophrenia and bipolar I disorder in adults (per background/usage notes)

Key safety noteContraindicated in patients using opioids or undergoing acute opioid withdrawal; boxed warning: increased mortality in elderly patients with dementia-related psychosis

Level of Care — Outpatient/Pharmacologic

Treatment Modalities

Pharmacotherapy (antipsychotic with opioid antagonist)

Contraindications: Do not administer Lybalvi to patients using opioids or undergoing acute opioid withdrawal; when administered with lithium or valproate, refer to the lithium or valproate prescribing information for contraindications.

Policy Summary

PayerHealth Net

PolicyOlanzapine/Samidorphan (Lybalvi) clinical coverage criteria

Policy CodePolicy N/A

Change TypeMaterial amendments to step therapy and exclusions

Effective DateSep 1, 2021

Next Review DateN/A

Key ActionSubmit prior authorization with diagnosis, age ≥18, required documentation, evidence of prior therapy or applicable state bypass, and dosing within 20 mg/10 mg per day.

SourceLink

On This Page

Step Therapy

Step Therapy Requirements and State Exceptions

Step therapy is required unless an exception or state‑level restriction applies. Usual requirement: failure of a 4‑week trial of olanzapine or a 4‑week trial of one preferred atypical antipsychotic (e.g., aripiprazole, ziprasidone, quetiapine, risperidone) at up to maximally indicated doses, unless clinically significant adverse effects occur or all are contraindicated. Dose limit: do not exceed olanzapine 20 mg / samidorphan 10 mg (1 tablet) per day. Approval duration: typically 12 months.

Typical step: 4‑week trial of olanzapine OR 4‑week trial of one preferred atypical antipsychotic at therapeutic doses
Dose limit: olanzapine/samidorphan ≤ 20 mg/10 mg per day
Approval duration: 12 months