ZYPREXA RELPREVV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYPREXA RELPREVV (ZYPREXA RELPREVV).
Olanzapine pamoate is a second-generation antipsychotic that antagonizes dopamine D2 and serotonin 5-HT2A receptors. It also binds to adrenergic α1, histamine H1, and muscarinic M1 receptors.
| Metabolism | Primarily metabolized by direct glucuronidation (UGT1A4) and oxidative metabolism via CYP1A2, with minor contributions from CYP2D6 and CYP3A4. |
| Excretion | Approximately 57% of the dose is excreted in urine (30% as unchanged drug, 27% as metabolites) and 30% in feces (primarily as metabolites). |
| Half-life | The terminal elimination half-life ranges from 30 to 60 days (mean ~45 days) after intramuscular injection, consistent with extended release from the depot formulation. |
| Protein binding | Approximately 93% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1000–1500 L (14–22 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Bioavailability is 100% for the intramuscular route as it is a parenteral depot formulation; oral olanzapine bioavailability is 60% (not applicable for this formulation). |
| Onset of Action | Therapeutic effect typically begins within 2–3 days following intramuscular injection, with peak plasma concentrations reached at a median of 7 days post-dose. |
| Duration of Action | Duration of action is approximately 2–4 weeks for symptom control, corresponding to the dosing interval (every 2 weeks or monthly). |
210 mg intramuscular injection every 2 weeks; range 150-300 mg; max 300 mg per dose. For olanzapine-naive patients, establish tolerability with oral olanzapine before initiation.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min); use caution. |
| Liver impairment | Child-Pugh Class A or B: no adjustment recommended. Child-Pugh Class C: use caution; lower starting dose may be considered due to potential increased exposure. |
| Pediatric use | Safety and efficacy not established in pediatric patients; not recommended for use under 18 years of age. |
| Geriatric use | Initial dose of 150 mg intramuscularly every 4 weeks; may consider slower titration. Monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. Not recommended for elderly patients with dementia-related psychosis due to increased mortality risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYPREXA RELPREVV (ZYPREXA RELPREVV).
| Breastfeeding | Olanzapine is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.2–0.84. The estimated infant dose via breast milk is about 1-2% of the maternal weight-adjusted dose. Limited data suggest no consistent adverse effects in breastfed infants, but monitoring for sedation, irritability, and poor feeding is recommended. Breastfeeding is generally acceptable with careful infant monitoring. |
| Teratogenic Risk | First trimester: Limited data, but olanzapine is associated with a small increased risk of neural tube defects and possibly other malformations based on some studies; however, the absolute risk remains low. Second and third trimesters: Exposure may lead to extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremors, somnolence, respiratory distress, and feeding difficulties. Overall, risk is considered moderate; benefits may outweigh risks in severe maternal psychiatric illness. |
■ FDA Black Box Warning
Post-injection delirium/sedation syndrome (PDSS): Following injection, patients may experience symptoms consistent with olanzapine overdose, including sedation, coma, and delirium. Patients must be observed for at least 3 hours after each injection in a registered healthcare facility.
| Serious Effects |
["Known hypersensitivity to olanzapine or any component of the formulation"]
| Precautions | ["Post-injection delirium/sedation syndrome (PDSS)","Elderly patients with dementia-related psychosis: increased risk of death","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Metabolic changes: hyperglycemia, dyslipidemia, weight gain","Orthostatic hypotension","Seizures","Leukopenia/neutropenia","Dysphagia","Hyperprolactinemia"] |
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| Fetal Monitoring | Maternal: Weight, body mass index (BMI), blood pressure, blood glucose, lipid profile, and signs of extrapyramidal symptoms or tardive dyskinesia. Fetal/neonatal: Third-trimester exposure necessitates monitoring for neonatal extrapyramidal symptoms and withdrawal syndromes. Consider fetal ultrasound for structural anomalies if first-trimester exposure occurred. |
| Fertility Effects | Olanzapine may increase serum prolactin levels, which can lead to galactorrhea, amenorrhea, and potential reversible infertility in women. In men, hyperprolactinemia may cause decreased libido, erectile dysfunction, and reduced sperm quality. These effects are generally reversible upon dose reduction or discontinuation. |