ZYPREXA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYPREXA (ZYPREXA).
Olanzapine is an atypical antipsychotic that antagonizes dopamine D2 and serotonin 5-HT2A receptors, with higher affinity for 5-HT2A than D2. It also blocks histamine H1, alpha-1 adrenergic, and muscarinic M1 receptors.
| Metabolism | Primarily metabolized by direct glucuronidation and oxidation via CYP1A2; minor pathways involve CYP2D6 and flavin-containing monooxygenase. |
| Excretion | Primarily hepatic metabolism via CYP1A2 and CYP2D6; ~7% excreted unchanged in urine, ~57% in urine as metabolites, ~30% in feces (mostly metabolites). |
| Half-life | Terminal elimination half-life ~30 hours (range 21–54 h) in adults, allowing once-daily dosing; steady-state reached in ~5–7 days. Half-life prolonged in elderly, females, and hepatic impairment. |
| Protein binding | ~93% bound, mainly to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Vd ~1000–1500 L (14–21 L/kg), indicating extensive extravascular distribution (large tissue binding). |
| Bioavailability | Oral: ~60% (due to first-pass metabolism); IM: 100%. |
| Onset of Action | IM injection: therapeutic effect within 15–30 minutes for acute agitation; oral: symptomatic improvement may begin within 1–2 weeks, full antipsychotic effect often requires 4–6 weeks. |
| Duration of Action | IM: duration of sedation 2–4 hours; oral: duration of action ~24 hours due to long half-life, supporting once-daily dosing. |
5-10 mg orally once daily; may increase by 5 mg/day at intervals of at least 1 week; maximum 20 mg/day.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for renal impairment; not removed by hemodialysis. |
| Liver impairment | Child-Pugh A or B: initiate 5 mg once daily, increase with caution. Child-Pugh C: no data. |
| Pediatric use | Adolescents (13-17 years): initiate 2.5-5 mg orally once daily; target 10-12.5 mg/day based on response and tolerability. |
| Geriatric use | Initiate at 5 mg once daily; increase cautiously; monitor for orthostatic hypotension and sedation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYPREXA (ZYPREXA).
| Breastfeeding | Olanzapine is excreted in human milk; estimated infant dose is about 1.8% of maternal weight-adjusted dose. Milk-to-plasma ratio approximately 0.2. Use with caution, monitor infant for sedation, irritability, and poor feeding. |
| Teratogenic Risk | First trimester: Limited data, no consistent association with major malformations. Second/Third trimesters: Risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates after third trimester exposure, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Olanzapine is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to olanzapine or any component of the formulation"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Suicidal thoughts or behaviors (monitor closely)","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Hyperglycemia and diabetes mellitus","Dyslipidemia","Weight gain","Orthostatic hypotension","Leukopenia/neutropenia/agranulocytosis","Seizures","Body temperature dysregulation","Dysphagia","Cognitive and motor impairment"] |
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| Fetal Monitoring |
| Monitor maternal blood glucose, lipid profile, weight gain, and blood pressure; assess for gestational diabetes and excessive weight gain. Fetal monitoring: standard prenatal care; consider ultrasound for growth if concerns. Neonatal monitoring for extrapyramidal symptoms and withdrawal after delivery. |
| Fertility Effects | May cause hyperprolactinemia, which can lead to menstrual irregularities, galactorrhea, and reduced fertility. Restores normal prolactin levels upon discontinuation. |