THORAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THORAZINE (THORAZINE).
Antagonist at dopamine D2 receptors in the mesolimbic pathway; also blocks alpha-adrenergic, histaminergic, and muscarinic receptors.
| Metabolism | Primarily hepatic via CYP2D6, with major metabolites including 7-hydroxychlorpromazine and sulfoxide derivatives. |
| Excretion | Renal (biliary/fecal): ~70% renal as metabolites, ~30% biliary/fecal; <1% unchanged in urine. |
| Half-life | Terminal elimination half-life: 15–30 hours (mean ~24 h); may extend to 40+ h in elderly or hepatic impairment. |
| Protein binding | Highly protein-bound: 95–99%, primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd: 10–20 L/kg (approx. 700–1400 L in 70 kg); extensive tissue distribution. |
| Bioavailability | Oral: 10–30% (high first-pass metabolism); IM: 75–90%; IV: 100%. |
| Onset of Action | Oral: 30–60 minutes; IM: 15–30 minutes; IV: 5–10 minutes. |
| Duration of Action | Oral: 4–6 hours (antipsychotic effect persists 6–12 h); IM: 4–8 hours; IV: 3–4 hours. Sedative effects may last up to 24 h. |
| Molecular Weight | 318.86 |
10-25 mg orally 3-4 times daily; maximum 800 mg/day. 25-50 mg intramuscularly every 4-6 hours.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment. |
| Liver impairment | Contraindicated in severe liver disease; mild-moderate impairment: reduce dose by 50%. |
| Pediatric use | 0.5 mg/kg orally every 4-6 hours as needed; maximum 40 mg/day for children under 5 years, 75 mg/day for children 5-12 years. |
| Geriatric use | Initiate at 10-25 mg orally once daily; increase gradually; monitor for hypotension and anticholinergic effects. |
| 1st trimester | Limited human data; risk of congenital malformations not established; avoid if possible. |
| 2nd trimester | Use with caution; may cause maternal hypotension and fetal hypoxia. |
| 3rd trimester | Risk of extrapyramidal symptoms and/or withdrawal syndrome in neonates; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for THORAZINE (THORAZINE).
| Placental transfer | Chlorpromazine crosses the placenta; detectable in fetal plasma and amniotic fluid. |
| Breastfeeding | Chlorpromazine excreted into breast milk in small amounts; monitor infant for drowsiness, poor feeding, or extrapyramidal effects; use with caution. |
| Lactation Rating |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis due to increased risk of cerebrovascular events and infection.
| Serious Effects |
Comatose statesCNS depressionKnown hypersensitivity to phenothiazinesConcomitant use of large amounts of CNS depressants
| Precautions | Tardive dyskinesia with long-term use; neuroleptic malignant syndrome; leukopenia/neutropenia/agranulocytosis; prolonged QT interval; seizure threshold lowering; orthostatic hypotension; anticholinergic effects; hepatic injury; ocular toxicity; photosensitivity. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Grapefruit juice may increase chlorpromazine levels via CYP3A4 inhibition. Concurrent use with caffeine may reduce antipsychotic efficacy. High-fat meals can decrease absorption; take on an empty stomach or with a light meal for consistent effects. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data, but potential for neural tube defects and cardiovascular anomalies based on animal studies. Second/third trimester: Risk of extrapyramidal symptoms and withdrawal in neonates. Avoid in third trimester near delivery due to risk of neonatal jaundice and dystonic reactions. |
| Fetal Monitoring | Maternal: Monitor blood pressure (risk of hypotension), ECG (QTc prolongation), liver function tests, and CBC for agranulocytosis. Fetal: Ultrasound for growth and anatomy, fetal heart rate monitoring near term. |
| Fertility Effects | Chlorpromazine can elevate prolactin levels, leading to galactorrhea, menstrual irregularities, and potential inhibition of ovulation. May impair fertility, but effects are reversible upon discontinuation. |
| Clinical Pearls | Thorazine (chlorpromazine) is a first-generation antipsychotic with strong anticholinergic, antihistaminergic, and antiadrenergic effects. It is particularly useful for hiccups, acute porphyria, and severe nausea/vomiting. Monitor for extrapyramidal symptoms, especially in elderly patients. Avoid concurrent use with other CNS depressants (e.g., alcohol, benzodiazepines) due to additive sedation. QT prolongation is possible; baseline ECG recommended, especially in patients with electrolyte abnormalities or on other QTc-prolonging drugs. Risk of neuroleptic malignant syndrome requires vigilance. Orthostatic hypotension is common; caution when changing positions. Thorazine can lower seizure threshold; use cautiously in epilepsy. |
| 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 you react. · Rise slowly from sitting or lying positions to prevent dizziness. · Avoid alcohol and other sedatives while taking this medication. · Report any unusual muscle stiffness, fever, confusion, or changes in heartbeat immediately. · Protect skin from excessive sun exposure; use sunscreen and wear protective clothing. · Use sugarless candy or gum for dry mouth; maintain good oral hygiene. · Store at room temperature away from light and moisture. |