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. |
| Molecular Weight | 383.51 |
| Action Class | Atypical Antipsychotic |
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 | Limited human data; animal studies show some adverse effects. Use only if potential benefit justifies risk to fetus. May increase risk of congenital anomalies, especially if used with other antipsychotics. |
| 2nd trimester | Limited human data; animal studies show some adverse effects. Use only if potential benefit justifies risk to fetus. Monitor for gestational diabetes and excessive weight gain. |
| 3rd trimester | Exposure may cause extrapyramidal and/or withdrawal symptoms in neonates. Avoid use near term unless necessary. Monitor neonate for agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder. |
Clinical note
Comprehensive clinical and safety monograph for SEROQUEL (SEROQUEL).
| Placental transfer | Quetiapine crosses the placenta; detectable in cord blood. Fetal plasma levels may reach up to 50% of maternal levels. |
| Breastfeeding | Quetiapine is excreted into human milk in low amounts. Relative infant dose is approximately 0.1% of maternal weight-adjusted dose. Monitor infant for drowsiness, poor feeding, and developmental milestones. Benefits of breastfeeding generally outweigh low risk; however, caution recommended in infants with compromised renal or hepatic function. |
■ 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.
| Common Effects | Somnolence, Dizziness, Dry mouth, Constipation, Dyspepsia, Weight gain, Increased appetite, Asthenia, Headache, Orthostatic hypotension |
| Serious Effects | Increased mortality in elderly patients with dementia-related psychosis, Suicidal thoughts or behaviors, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Metabolic changes: hyperglycemia, diabetes mellitus, dyslipidemia, weight gain, Orthostatic hypotension and syncope, Seizures, Leukopenia, neutropenia, agranulocytosis, QT interval prolongation, Cataracts (lens changes) |
Hypersensitivity to quetiapine or any excipientsConcomitant use with CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, St. John's wort) decreases quetiapine levels
| 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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| Lactation Rating | L2 (Limited data, probably compatible) |
| 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. |
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase quetiapine serum levels via CYP3A4 inhibition. High-fat meals can increase the absorption of the XR formulation and should be avoided; take XR on an empty stomach or with a light meal. Alcohol can potentiate sedative effects and should be avoided. Caffeine may reduce the sedative effect; advise limiting caffeine intake if excessive sedation is problematic. |
| Clinical Pearls | Quetiapine (Seroquel) is unique among atypical antipsychotics for its dose-dependent receptor profile: at low doses (25–200 mg/day), strong H1 and α1 antagonism produces sedation and antihistaminic effects; at moderate doses (300–600 mg/day), 5-HT2A and D2 antagonism contributes to antipsychotic efficacy; at high doses (600–800 mg/day), D2 occupancy becomes sufficient to treat psychosis. The extended-release (XR) formulation should be used for once-daily dosing and may cause less peak-related sedation. Monitor for metabolic side effects—weight gain, hyperglycemia, dyslipidemia—and orthostatic hypotension, especially during dose titration. Due to risk of cataracts, baseline and follow-up eye exams are recommended. QT prolongation is possible; avoid in patients with uncorrected hypokalemia or hypomagnesemia. Taper gradually to avoid withdrawal symptoms. |
| Patient Advice | Take exactly as prescribed; do not increase or stop abruptly without talking to your doctor. · This medication can cause drowsiness; avoid driving or operating machinery until you know how it affects you. · XR tablets should be swallowed whole, not crushed or chewed, and taken without food or with a light meal preferably in the evening. · Report any unusual movements, muscle stiffness, fever, or confusion to your doctor immediately as these could be signs of neuroleptic malignant syndrome. · Check blood pressure regularly; rise slowly from sitting or lying to prevent dizziness. · Regular blood tests may be needed to monitor blood sugar, cholesterol, and liver function. · Avoid alcohol and grapefruit juice while on this medication. · Use effective contraception if of childbearing age; inform your doctor if pregnant or breastfeeding. · Do not take other medications without consulting your doctor, especially those that affect heart rhythm. |