SEROQUEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEROQUEL (SEROQUEL).
Antagonist at dopamine D2 and serotonin 5-HT2A receptors; also blocks histamine H1 and adrenergic α1 receptors.
| Metabolism | Primarily hepatic via CYP3A4; minor pathways via CYP2D6; active metabolite norquetiapine. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged renally. Metabolites excreted in urine (73%) and feces (20%). |
| Half-life | Terminal elimination half-life approximately 7 hours for quetiapine; for metabolite N-desalkylquetiapine (norquetiapine), approximately 12 hours. Steady-state reached within 2 days. |
| Protein binding | Quetiapine: 83% bound to serum proteins; active metabolite norquetiapine: similar binding. |
| Volume of Distribution | Mean Vd: 10 ± 4 L/kg; large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability: ~100% (immediate-release); food does not significantly affect absorption. Relative bioavailability of extended-release compared to immediate-release: approximately 85% at same daily dose. |
| Onset of Action | Oral: Sedative effects within 1-2 hours; antipsychotic effects may take days to weeks; antidepressant action (adjunctive) may be observed within 1-2 weeks. |
| Duration of Action | Dosing typically twice daily due to short half-life; extended-release formulation (Seroquel XR) allows once-daily dosing. Duration of sedative effect: 4-6 hours immediate-release. |
Initial: 25 mg twice daily; titrate by 25-50 mg twice daily on day 2 and 3 to target 300-400 mg daily in 2-3 divided doses. Maintenance: 400-800 mg daily. Maximum: 800 mg daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, start at 25 mg daily, titrate by 25 mg/day increments at 3-4 day intervals. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B or C: Start at 25 mg daily, increase by 25 mg/day to a maximum of 150 mg daily. |
| Pediatric use | Adolescents (13-17 years): Initial 25 mg twice daily; titrate to target 400-600 mg daily in 2-3 divided doses. Maximum 800 mg daily. |
| Geriatric use | Initial: 25 mg daily; increase by 25 mg/day at 2-3 day intervals to target dose. Usual effective dose: 100-200 mg daily. Maximum 400 mg daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEROQUEL (SEROQUEL).
| Breastfeeding | Quetiapine is excreted into breast milk with a mean infant plasma concentration about 18% of maternal (M/P ratio ~0.3-0.5). Limited reports of drowsiness, poor feeding; monitor for sedation, weight gain. The benefits of breastfeeding likely outweigh low risk; use lowest effective maternal dose. |
| Teratogenic Risk | First trimester: Limited data; possible increased risk of congenital malformations, particularly cardiac defects, from a single large study (OR 2.1 for major malformations). Second/third trimester: Risk of extrapyramidal symptoms, withdrawal (e.g., agitation, hypertonia), and neonatal adaptation syndrome. Animal studies show fetal toxicity at high doses. Causality not confirmed; risk-benefit required. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis; increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Known hypersensitivity to quetiapine or any excipients"]
| Precautions | ["Cerebrovascular adverse events in elderly dementia patients","neuroleptic malignant syndrome","tardive dyskinesia","metabolic changes (hyperglycemia, dyslipidemia, weight gain)","orthostatic hypotension","seizures","leukopenia/neutropenia","cataracts","body temperature dysregulation","dysphagia"] |
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| Fetal Monitoring | Gestational diabetes screening at 24-28 weeks due to weight gain risk. Monitor for extrapyramidal symptoms, sedation, blood pressure, weight. Fetal: growth ultrasound (prenatal, third trimester) for possible macrosomia or growth restriction. Neonatal: Observe for extrapyramidal signs, withdrawal, respiratory distress, feeding difficulties. |
| Fertility Effects | Elevated prolactin levels may cause menstrual irregularities, anovulation, galactorrhea, and reduce fertility. Effect is dose-dependent; hyperprolactinemia can be managed by dose reduction or switching. Reversible upon discontinuation. |