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. |
| Molecular Weight | 383.51 |
| Action Class | Atypical Antipsychotic |
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 | Limited human data; animal studies show developmental toxicity at high doses. Risk cannot be excluded. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for adverse effects on fetal growth and neurodevelopment. Use only if clearly needed. |
| 3rd trimester | Risk of neonatal withdrawal symptoms (agitation, hypertonia, tremors, feeding difficulty) and extrapyramidal signs. Use only if benefit outweighs risk. |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause sedation cataracts and metabolic changes.
| FDA category | Animal |
| Placental transfer | Quetiapine crosses the placenta; fetal plasma concentrations are approximately 50% of maternal concentrations. |
| Breastfeeding |
■ 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 | Tardive dyskinesia, Neuroleptic malignant syndrome, Hyperglycemia and diabetes mellitus, Dyslipidemia, Weight gain, Orthostatic hypotension, Seizures, Leukopenia/neutropenia, Cataracts (lens changes), QT prolongation, Increased mortality in elderly patients with dementia-related psychosis |
Hypersensitivity to quetiapine or any component of the formulationConcurrent use with dofetilide or other drugs that prolong QT interval
| 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 |
Loading safety data…
| Quetiapine is excreted into human breast milk in low amounts. Relative infant dose is estimated <1%. Monitor infant for drowsiness, poor feeding, and developmental milestones. Avoid if infant has hepatic impairment or if mother requires high doses. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| 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. |
| 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. |
| Food/Dietary | Grapefruit and grapefruit juice may increase quetiapine levels; avoid concurrent use. Alcohol can potentiate sedative effects; avoid or limit. The extended-release tablets should be taken without food or with a light meal (less than 300 calories) to ensure consistent absorption. |
| Clinical Pearls | Titrate slowly to minimize orthostatic hypotension and sedation. Monitor for QTc prolongation, especially when combined with other QT-prolonging agents. Blood glucose and lipid panels should be assessed at baseline and regularly during therapy. Extrapyramidal symptoms are less common than with typical antipsychotics but may occur at higher doses. This drug has high affinity for histamine H1 receptors, causing significant sedation; administer at bedtime when possible. Avoid abrupt discontinuation; taper gradually to prevent withdrawal symptoms including nausea, insomnia, and anxiety. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · May cause drowsiness; avoid driving or operating heavy machinery until you know how this medicine affects you. · Rise slowly from sitting or lying positions to prevent dizziness. · Notify your doctor immediately if you experience rapid heartbeat, fainting, or unusual movements of the face, tongue, or jaw. · Avoid alcohol and grapefruit juice while taking this medication. · Regular blood tests are necessary to monitor blood sugar, cholesterol, and weight. |