ZYPREXA ZYDIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).
Olanzapine is an atypical antipsychotic with high affinity for serotonin 5-HT2A and 5-HT2C receptors, dopamine D1-D4 receptors, muscarinic M1-M5 receptors, histamine H1 receptors, and alpha1-adrenergic receptors. Antagonism at D2 and 5-HT2A receptors is primarily responsible for its antipsychotic effects.
| Metabolism | Primarily metabolized by liver via direct glucuronidation and CYP1A2-mediated oxidation. Minor pathways include CYP2D6 and flavin-containing monooxygenase 3 (FMO3). |
| Excretion | Renal: ~57% (as metabolites); Fecal: ~30% (as metabolites); Unchanged olanzapine in urine <7%. |
| Half-life | Terminal elimination half-life: ~30 hours (range 21–54 hours) in healthy adults; prolonged in elderly (mean 51.8 h) and hepatic impairment. |
| Protein binding | ~93% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Mean Vd: 14–18 L/kg (1000–1200 L), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability: ~60–80% (first-pass metabolism). ODT has similar bioavailability to standard olanzapine tablets. |
| Onset of Action | Orally disintegrating tablet (ODT): Peak plasma concentration reached in ~5–6 hours; antipsychotic effect onset may be observed within 1–2 weeks. |
| Duration of Action | Dosing interval is typically once daily due to long half-life; steady-state achieved after ~1 week. Duration of clinical effect persists for at least 24 hours. |
| Molecular Weight | 312.43 |
| Action Class | Atypical Antipsychotic; Thienobenzodiazepine |
10 mg orally once daily; range 5-20 mg once daily. Initial dose 5-10 mg, titrate by 5 mg weekly. Maximum 20 mg/day. Orally disintegrating tablet.
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | No dose adjustment required for renal impairment. For severe renal impairment (CrCl <10 mL/min), use with caution and consider lower initial dose of 5 mg. |
| Liver impairment | Child-Pugh Class A or B: Use with caution, consider lower initial dose (5 mg) and slower titration. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Adolescents (13-17 years) with schizophrenia or bipolar I disorder: initial 2.5-5 mg orally once daily; target 10 mg/day; range 2.5-20 mg/day. For manic or mixed episodes: start 2.5 mg, increase by 2.5-5 mg daily to target 10 mg. Weight-based: not applicable. |
| Geriatric use | Elderly patients: lower initial dose of 5 mg orally once daily; titrate cautiously. Increased sensitivity to orthostatic hypotension, sedation, and anticholinergic effects. Monitor for falls and extrapyramidal symptoms. |
| 1st trimester | Olanzapine crosses the placenta. First-trimester exposure data are limited but do not suggest a major teratogenic risk; however, increased risk of neural tube defects and other malformations cannot be excluded. Use only if potential benefit justifies risk. |
| 2nd trimester | Mid-trimester exposure may be associated with maternal metabolic effects (weight gain, hyperglycemia) and should be monitored. Risk-benefit assessment required. |
| 3rd trimester | Third-trimester use may cause neonatal extrapyramidal symptoms, withdrawal, or sedation (irritability, hypertonia, feeding difficulties). Taper if possible before delivery. |
Clinical note
Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).
| Placental transfer | Olanzapine crosses the placenta extensively; fetal concentrations approximate maternal levels. Molecular weight (312.43 Da) and lipophilicity facilitate transfer. |
| Breastfeeding |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ZYPREXA ZYDIS is not approved for the treatment of dementia-related psychosis.
| Common Effects | Somnolence, Weight gain, Increased appetite, Dry mouth, Constipation, Dizziness, Akathisia, Asthenia, Peripheral edema, Dyspepsia |
| Serious Effects | Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia, Hyperglycemia and Diabetes Mellitus, Hyperlipidemia, Weight gain (significant), Orthostatic hypotension, Seizures, Leukopenia/Neutropenia/Agranulocytosis, QT prolongation (rare), Venous thromboembolism, Cerebrovascular adverse events in elderly dementia patients, Increased mortality in elderly patients with dementia-related psychosis |
Known hypersensitivity to olanzapine or any excipientsHistory of neuroleptic malignant syndrome (NMS)Severe central nervous system depressionComatose statesNarrow-angle glaucoma
| Precautions | Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Hyperglycemia and diabetes mellitus, Dyslipidemia, Weight gain, Orthostatic hypotension, Seizures, Leukopenia/neutropenia/agranulocytosis, Cognitive and motor impairment, Suicide risk, Dysphagia, Anticholinergic effects, Body temperature dysregulation |
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| Olanzapine is excreted into breast milk in low levels (infant dose ~2% of maternal weight-adjusted dose). Case reports of somnolence, irritability, and poor feeding. Monitor infant for sedation and weight gain. Preferred over other atypicals in breastfeeding due to lower risk, but consider alternative if maternal psychosis requires high doses. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category C. First trimester: limited data; potential risk of neural tube defects? Second and third trimesters: exposure may lead to extrapyramidal symptoms and/or withdrawal symptoms in neonates including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders. Risk of gestational diabetes, weight gain, and hypertension. |
| Fetal Monitoring | Maternal: weight, blood pressure, blood glucose, lipid profile, signs of extrapyramidal symptoms, sedation, and metabolic syndrome. Fetal/neonatal: growth parameters via ultrasound, monitoring for neonatal abstinence syndrome after birth. |
| Fertility Effects | May cause hyperprolactinemia, potentially impairing fertility via inhibition of gonadotropin-releasing hormone. Reversible upon discontinuation. |
| Food/Dietary | No specific food restrictions reported. However, olanzapine may cause increased appetite and weight gain; monitor caloric intake. Grapefruit juice may slightly increase olanzapine concentration (not considered clinically significant). Avoid alcohol due to additive CNS depression. |
| Clinical Pearls | ZYPREXA ZYDIS (olanzapine orally disintegrating tablet) is indicated for schizophrenia and bipolar I disorder (acute mixed/manic episodes, maintenance). Rapidly dissolves on tongue; no water needed. Bioequivalent to standard olanzapine tablets. Monitor for metabolic syndrome (weight gain, hyperglycemia, dyslipidemia). Highest risk of weight gain among atypicals. Also for treatment-resistant depression in combination with fluoxetine. Avoid use with other anticholinergics (paralytic ileus). QT prolongation risk; avoid in electrolyte imbalance. Extrapyramidal symptoms less than haloperidol but can cause akathisia. Tardive dyskinesia possible with long-term use. Neuroleptic malignant syndrome rare but serious. Orthostatic hypotension, especially during titration. Caution in elderly with dementia-related psychosis (increased mortality). |
| Patient Advice | Do not push the tablet through the foil; peel back the foil and gently remove the tablet. · Place the tablet on your tongue; it will dissolve rapidly and can be swallowed with saliva. · Do not chew or crush the tablet; no water is needed to take it. · May cause drowsiness; avoid driving or operating machinery until you know how the medicine affects you. · Avoid alcohol as it may increase drowsiness and dizziness. · Report any significant weight gain, increased thirst or urination (signs of high blood sugar), or muscle stiffness and fever (NMS symptoms). · Do not stop taking this medication suddenly; withdrawal symptoms may occur. · Keep out of reach of children; store at room temperature in a dry place. |