BOXED WARNING Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis.
FDA dosing
Population
Start
Target
Max
Schizophrenia
Adults
5/10 or 10/10 mg QD
10/10, 15/10, or 20/10 mg QD
20/10 mg QD
Bipolar I mania/mixed, monotherapy
Adults
10/10 or 15/10 mg QD
10/10–20/10 mg QD (maintenance 5/10–20/10)
20/10 mg QD
Bipolar I mania/mixed, adjunct to lithium/valproate
Adults
10/10 mg QD
10/10, 15/10, or 20/10 mg QD
20/10 mg QD
Titration Schizophrenia & adjunct: adjust at weekly intervals (5-mg olanzapine steps). Bipolar monotherapy (acute): ≥24 h between adjustments.
Renal Not recommended in end-stage renal disease.
Hepatic No adjustment needed - exposure is higher in moderate hepatic impairment but not expected to be clinically relevant; severe hepatic impairment not studied
Opioid-free interval required before starting: ≥7 days (short-acting) / ≥14 days (long-acting opioids).
Instructions
Once daily with or without food, as a single tablet — do not divide tablets or combine strengths
Opioid users: delay initiation ≥7 days after last short-acting opioid, ≥14 days after last long-acting opioid
Start 5/10 mg QD and escalate slowly if hypotension-prone, slower olanzapine metabolism, or olanzapine-sensitive
Available strengths
tab 5/10, 10/10, 15/10, 20/10 mg
Contraindications
Patients using opioids — samidorphan (opioid antagonist) precipitates withdrawal; blockade also invites fatal overdose from attempts to override it
Patients undergoing acute opioid withdrawal
Cautions
Precipitation of severe opioid withdrawal in opioid-dependent patients (may require hospitalization)
Vulnerability to life-threatening opioid overdose: overriding the blockade with high/repeated opioid doses can be fatal, especially as blockade wanes after stopping; prior chronic users lose tolerance — emergency opioid anesthesia/analgesia requires discontinuing Lybalvi with trained monitoring
Cerebrovascular events incl. fatal stroke in elderly dementia patients
Adjunct to lithium/valproate: dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia
Pregnancy Third-trimester exposure → neonatal EPS/withdrawal; no established olanzapine birth-defect risk; no human samidorphan data; pregnancy registry 1-866-961-2388.
Lactation Present in milk at low levels (<1% weight-adjusted maternal dose); monitor infant for sedation, irritability, poor feeding, EPS.