QUETIAPINE FUMARATE
Clinical safety rating: safe
Strong CYP3A4 inhibitors may increase levels Can cause sedation cataracts and metabolic changes.
Antagonist at serotonin 5-HT2A, dopamine D2, histamine H1, alpha1-adrenergic, and muscarinic M1 receptors. Also partial agonist at serotonin 5-HT1A and dopamine D2 receptors (depending on dose).
| Metabolism | Primarily hepatic via CYP3A4; minor via CYP2D6. Active metabolite: norquetiapine. Substrate of P-glycoprotein. |
| Excretion | Renal: 73% (20% unchanged, remainder as metabolites); Fecal: 21%; Approximately 5% excreted in feces as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 6-7 hours (quetiapine) and 9-12 hours for the active metabolite norquetiapine; with extended-release formulation, effective half-life is ~7 hours due to slower absorption. Clinical steady-state achieved within 2 days. |
| Protein binding | Quetiapine: 83% bound to serum proteins (mainly albumin and alpha-1-acid glycoprotein); Norquetiapine: approximately 50% bound. |
| Volume of Distribution | Quetiapine: 10 ± 4 L/kg, indicating extensive tissue distribution; Steady-state Vd is 6-10 L/kg. |
| Bioavailability | Oral: Immediate-release: 100% (well absorbed; extensive first-pass metabolism reduces systemic availability to ~100% due to saturable first-pass? Actually absolute bioavailability is 100% for immediate-release; Extended-release: approximately 100% relative to immediate-release but with different absorption profile. |
| Onset of Action | Immediate-release: Oral: 1-2 hours for sedation; antipsychotic effect takes 1-2 weeks. Extended-release: Oral: 2-3 hours for sedation; antipsychotic effect similarly delayed. |
| Duration of Action | Dosing interval: Immediate-release: 8-12 hours (t.i.d. or b.i.d.); Extended-release: 24 hours (once daily). Antipsychotic effect persists with regular dosing; sedation may last 4-6 hours post-dose. |
Immediate release: 25-100 mg orally twice daily, titrated as needed up to 400-800 mg/day divided twice daily. Extended release: 50-200 mg orally once daily, titrated up to 400-800 mg/day once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, reduce initial dose to 25 mg/day and titrate slowly, maximum 50 mg/day. |
| Liver impairment | Child-Pugh Class A or B: Start at 25 mg/day immediate release, increase by 25-50 mg/day. Child-Pugh Class C: Contraindicated or use with extreme caution, start at 12.5 mg/day immediate release, maximum 50 mg/day. |
| Pediatric use | Schizophrenia (13-17 years): 25 mg twice daily on day 1, then 50 mg twice daily on day 2, then 100 mg twice daily on day 3, target 400-800 mg/day. Bipolar mania (10-17 years): 25 mg twice daily on day 1, increase to 200-400 mg/day by day 5, maximum 600 mg/day. |
| Geriatric use | Start at 12.5-25 mg immediate release twice daily or 25 mg extended release once daily. Titrate slowly, increase by 25-50 mg per day, maximum 400 mg/day for extended release or 200 mg/day for immediate release in patients >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause sedation cataracts and metabolic changes.
| FDA category | Animal |
| Breastfeeding | Limited data: Quetiapine is excreted into human milk; M/P ratio not well established; relative infant dose estimated <1% based on limited cases; monitor infant for sedation, feeding difficulties, and developmental milestones; consider breastfeeding only if benefit outweighs risk. |
| Teratogenic Risk | First trimester: Epidemiologic studies show no consistent increased risk of major malformations, but data are limited; second and third trimesters: Exposure may be associated with extrapyramidal and/or withdrawal symptoms in neonates (e.g., agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress); risk of toxemia of pregnancy is not established. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis due to cardiovascular or infectious events; not approved for dementia-related psychosis. Suicidality and antidepressant drugs: increased risk of suicidal thoughts and behavior in children, adolescents, and young adults.
| Common Effects | bipolar disorder |
| Serious Effects |
["Known hypersensitivity to quetiapine or excipients","Concomitant use with strong CYP3A4 inhibitors or inducers (e.g., ritonavir, ketoconazole, carbamazepine, phenytoin) due to significant drug interactions"]
| Precautions | ["Cerebrovascular events in elderly dementia patients","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Metabolic effects (hyperglycemia, dyslipidemia, weight gain)","Orthostatic hypotension and syncope","Leukopenia/neutropenia/agranulocytosis","Seizures","Cataracts","Hypothyroidism","Hyperprolactinemia","QT prolongation","Dysphagia","Suicidality"] |
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| Fetal Monitoring | Maternal: Weight gain, blood pressure, blood glucose, lipid profile, signs of tardive dyskinesia, extrapyramidal symptoms, and sedation; Fetal/Neonatal: Fetal growth ultrasound (consider baseline and serial if prolonged use), neonatal adaptation monitoring for extrapyramidal/withdrawal symptoms. |
| Fertility Effects | Quetiapine may increase prolactin levels (though less than some antipsychotics), potentially causing galactorrhea, amenorrhea, or gynecomastia, which may transiently reduce fertility; effects reversible upon dose reduction or discontinuation. |