Samidorphan

in LYBALVI

Open Samidorphan in the interactive console ↗

Pronunciation: sam-i-DOR-fan

Samidorphan ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Samidorphan ballicule

Samidorphan mascot mnemonic cartoon — Visual mnemonic: Samidorphan mascot
**“Semi-orphan / Semi-door fit-in”**
Ameliorates olanzapine-induced weight gain → helps you fit through doors
Dilated pupils (as with opioid withdrawal) → symbol for mu opioid antagonist

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.

Samidorphan molecular structure (skeletal formula) — Molecular structure: Samidorphan

FDA-approved for

schizophrenia/bipolar (with olanzapine) (2021)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis

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

Available strengths

tab 5/10, 10/10, 15/10, 20/10 mg

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

Cost

Samidorphan (IN LYBALVI)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	brand $/mo	CostPlus
5/10 mg	tab	30 qd	—	$1,656.41	not offered
10/10 mg	tab	30 qd	—	$1,652.91	not offered
15/10 mg	tab	30 qd	—	$1,653.58	not offered
20/10 mg	tab	30 qd	—	$1,649.45	not offered

⚠ BOXED WARNING

Increased mortality in elderly patients with dementia-related psychosis

Principal riskPrecipitated withdrawal in the opioid-dependent

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger1 / 4

Sedation liability2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Defining liabilityPrecipitated opioid withdrawal, opioid blockade and somnolence

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