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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THORAZINE (THORAZINE).
| Breastfeeding | Chlorpromazine is excreted into breast milk. M/P ratio unknown. Potential for infant drowsiness, hypotonia, and developmental delay. Use caution, especially in premature infants. Monitor infant for adverse effects. |
| 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. |
■ 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 states; severe CNS depression; bone marrow depression; hypersensitivity to chlorpromazine or other phenothiazines; concurrent use with large doses of CNS depressants (e.g., alcohol, barbiturates).
| 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. |
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| 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. |