olanzapine samidorphan

Antipsychotic

Brands: Lybalvi

Last reviewed 2025-12-29

Reviewed by PsychMed Editorial Team.

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Quick answers

What is olanzapine samidorphan?
Maintains olanzapine’s antipsychotic efficacy with approximately 2–3 kg less weight gain versus olanzapine alone, yet still requires full metabolic monitoring.
What is Lybalvi?
Lybalvi is a brand name for olanzapine samidorphan.
What is Lybalvi (olanzapine samidorphan) used for?
Label indications include: Schizophrenia (adults); Bipolar I disorder (acute/maintenance).
What drug class is Lybalvi (olanzapine samidorphan)?
Antipsychotic.
What is the mechanism of action of Lybalvi (olanzapine samidorphan)?
Combines olanzapine (D2/5-HT2A antagonist) with samidorphan, an opioid receptor antagonist intended to blunt olanzapine-associated weight gain.
What strengths does Lybalvi (olanzapine samidorphan) come in?
Oral tablets: 5/10 mg, 10/10 mg, 15/10 mg, 20/10 mg (olanzapine/samidorphan).
Is Lybalvi (olanzapine samidorphan) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.

Snapshot

Class: Antipsychotic
Common US brands: Lybalvi
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-29

Clinical Highlights

Maintains olanzapine’s antipsychotic efficacy with approximately 2–3 kg less weight gain versus olanzapine alone, yet still requires full metabolic monitoring. FDA-approved (2021) for adult schizophrenia and bipolar I disorder (acute manic/mixed episodes and maintenance); brand-only tablets combine 5–20 mg olanzapine with 10 mg samidorphan.

Often considered when olanzapine is clinically optimal but metabolic risk is high; payer authorization and structured metabolic counseling are common.
Not compatible with opioid therapy (pain treatment or opioid use disorder): alternatives are typically planned before initiation, and coordination with pain or addiction teams is common when future opioid needs are likely.
The compare view and the Lybalvi evidence feed can help when discussing metabolic trade-offs with teams or payers.
Schizophrenia (adults) (FDA 2021)
Bipolar I disorder (acute/maintenance) (FDA 2021)
Generic: No generic equivalent; wallet card supplied to communicate opioid contraindication.

Dosing & Formulations

Oral tablets: 5/10 mg, 10/10 mg, 15/10 mg, 20/10 mg (olanzapine/samidorphan). Switching from olanzapine typically matches the prior oral olanzapine dose (e.g., 10 mg → 10/10 mg); olanzapine-naïve patients commonly start 5/10 mg or 10/10 mg once daily.

Titration is typically in 5 mg olanzapine increments at ≥1-week intervals within the 5/10–20/10 mg daily range.
An opioid-free interval ≥7 days is required pre-initiation and post-discontinuation; perioperative pain plans and emergency protocols are typically coordinated in advance.
Strong CYP3A4 inhibitors/inducers are avoided; dose adjustments with moderate CYP3A4 or strong CYP1A2 inhibitors are often needed, and dosing is typically reassessed when smoking status changes.

Monitoring & Risks

Boxed warning: Increased mortality in elderly patients with dementia-related psychosis. Weight gain: Relative attenuation but ≥7% gain persists in ~17% of patients.

Somnolence: Approximately 20–25%; driving and fall precautions are commonly discussed.
Dry mouth/constipation: Anticholinergic effects similar to olanzapine.
Increased appetite: Reported in ~9–10% of patients.
Opioid withdrawal or analgesic failure if opioids are administered; provide wallet card and emergency guidance.
Patients should carry the wallet card and tell all clinicians (ER, dentists, surgeons) about Lybalvi before receiving any opioid or cough medicine with opioid ingredients.

Drug Interactions

Opioid agonists (analgesics, MAT) contraindicated—coordinate alternative analgesia. Strong CYP3A4 inhibitors/inducers markedly alter samidorphan exposure; combinations are generally avoided.

Strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) increase olanzapine exposure; dose reduction and monitoring for sedation/orthostasis are common.
Additive CNS depression with alcohol, benzodiazepines, sedative hypnotics.

Practice Notes

Pain management plans are typically documented, and wallet-card use is emphasized to communicate the opioid contraindication. Expect insurance hurdles: keep prior-authorization documentation on hand (olanzapine response, metabolic concern, opioid contraindication) and re-check coverage before dose changes.

Metabolic labs (baseline, 3 months, 6 months, annually) and lifestyle counseling are typically comparable to olanzapine.
Dosing is often re-evaluated when patients start/stop smoking or add metabolic inhibitors.
Coordinate long-term bipolar planning with the bipolar disorder hub and consult the LAI Navigator if depot switchbacks are under consideration.