TaperCommunityolanzapine
Boxed Warning
Increased mortality in elderly patients with dementia-related psychosis. Post-injection delirium/sedation syndrome with extended-release IM formulation (Zyprexa Relprevv).
Olanzapine is an atypical antipsychotic approved for schizophrenia and bipolar disorder (manic/mixed episodes, maintenance, and bipolar depression in combination with fluoxetine). It is effective but carries the highest metabolic risk among atypical antipsychotics.
2.5mg, 5mg, 10mg, 15mg, 20mg
Tablets: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg; Orally disintegrating tablets (Zydis): 5mg, 10mg, 15mg, 20mg; Intramuscular injection: 10mg; Extended-release injection (Zyprexa Relprevv): 210mg, 300mg, 405mg
Category C (risk cannot be ruled out)
Antagonist at dopamine D1–D4, serotonin 5-HT2A/2C/3/6, histamine H1, muscarinic M1–M5, and alpha-1 adrenergic receptors. The broad receptor profile contributes to efficacy but also drives significant weight gain and metabolic effects.
Tablets can be split. Weight gain reversal during tapering. Rebound insomnia common.
Slow gradual taper essential. Tablets available in small increments (2.5mg). Monitor for supersensitivity symptoms.
Toxicity
Significant metabolic syndrome (weight gain, hyperglycemia, diabetes, dyslipidemia — highest among atypical antipsychotics). Sedation. Orthostatic hypotension. Tardive dyskinesia. NMS rarely.
Pharmacokinetics
Well absorbed after oral administration. Bioavailability ~60% due to first-pass metabolism. Tmax ~6 hours. Food does not significantly affect absorption.
~1000 L (~14 L/kg)
Extensively metabolized hepatically via CYP1A2 (primary) and CYP2D6 via glucuronidation and oxidation. Major metabolites (10-N-glucuronide and 4'-N-desmethyl) are inactive.
Renal (~57%) and fecal (~30%). Approximately 7% excreted unchanged in urine.
~93%
~26 L/hr (apparent oral clearance)
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