Samidorphan
in LYBALVI
What it isMu opioid antagonist combined with olanzapine; schizophrenia and bipolar disorder.
Why this oneIt blunts olanzapine-associated weight gain while preserving efficacy.
What limits itIt precipitates withdrawal in opioid-dependent patients and blocks opioid analgesia. Olanzapine metabolic risk is reduced, not removed.
FDA-approved for
- schizophrenia/bipolar (with olanzapine) (2021)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Schizophrenia | Adult | 5/10 or 10/10 mg QD | 10/10–20/10 mg QD | 20/10 mg QD |
| Bipolar I (manic/mixed), monotherapy | Adult | 10/10 or 15/10 mg QD | 10/10–20/10 mg QD | 20/10 mg QD |
| Bipolar I, adjunct to lithium or valproate | Adult | 10/10 mg QD | 10/10–20/10 mg QD | 20/10 mg QD |
Titration Schizophrenia: adjust at weekly intervals; Bipolar I: intervals ≥24 h (5 mg olanzapine increments)
Renal Use not recommended in end-stage renal disease
Hepatic Undefined
Instructions
- Once daily with or without food
- Do not divide tablets or combine strengths
- Contraindicated with opioids: delay initiation ≥7 days after last short-acting and ≥14 days after last long-acting opioid
Contraindications
- Patients using opioids
- Patients undergoing acute opioid withdrawal
Cautions
- Cerebrovascular reactions (stroke) in elderly with dementia-related psychosis
- Precipitation of opioid withdrawal in opioid-dependent patients
- Vulnerability to life-threatening opioid overdose when attempting to override blockade
- Neuroleptic malignant syndrome
- DRESS
- Metabolic changes (hyperglycemia, dyslipidemia, weight gain)
- Tardive dyskinesia
- Orthostatic hypotension and syncope
- Falls
- Leukopenia, neutropenia, agranulocytosis
- Dysphagia
- Seizures
- Cognitive and motor impairment
Adverse reactions
- Common olanzapine-associated reactions include weight gain, somnolence, dry mouth, increased appetite (see label — not enumerated in captured section)
Pregnancy Pregnancy registry; third-trimester exposure risks EPS/withdrawal in neonate; olanzapine not associated with major birth defect risk
Lactation Olanzapine and samidorphan present in milk at low levels; reports of sedation, irritability, poor feeding, EPS in olanzapine-exposed infants
⚠ BOXED WARNING
- Increased mortality in elderly patients with dementia-related psychosis
Principal riskPrecipitated withdrawal in the opioid-dependent
Classes and tags
Clinical profile
Mechanism of action: Samidorphan ballicule
Open Samidorphan in the interactive console ↗
Memory aids: mascots and interaction avatars
Ameliorates olanzapine-induced weight gain → helps you fit through doors
Dilated pupils (as with opioid withdrawal) → symbol for mu opioid antagonist