CHLORPROMAZINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).
Antagonizes dopamine D2 receptors in the mesolimbic pathway; also blocks alpha-adrenergic, histamine H1, muscarinic, and serotonin receptors.
| Metabolism | Hepatic via CYP2D6 (major) and CYP1A2; undergoes glucuronidation and sulfation. |
| Excretion | Primarily hepatic metabolism; renal excretion accounts for ~20% as unchanged drug and metabolites, with ~6% unchanged; biliary/fecal excretion ~80%, mainly as metabolites. |
| Half-life | Terminal elimination half-life 30 ± 14 hours (range 20–70 hours); clinical context: requires multiple daily dosing in acute agitation, but long-acting IM formulations (not chlorpromazine) available; half-life increases with age and hepatic impairment. |
| Protein binding | 92–97% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Vd 10–15 L/kg (range 7–20 L/kg); clinical meaning: extensive tissue distribution, high binding to tissues, slow equilibration, long duration. |
| Bioavailability | Oral: 20–30% due to extensive first-pass metabolism; IM: 100% (absolute); IV: 100%. |
| Onset of Action | Oral: 30–60 minutes; IM: 15–30 minutes; IV: 5–10 minutes. |
| Duration of Action | Oral: 4–6 hours for antipsychotic effect, up to 24 hours for sedation; IM: 4–8 hours; IV: 2–4 hours; clinical notes: sedative effects may persist longer than antipsychotic effects. |
| Molecular Weight | 318.86 |
| Action Class | Typical Antipsychotics |
| Brand Substitutes | Clozine 100mg Tablet, Prozine 100mg Tablet, Sun Prazin 100mg Tablet, Zinetil 100mg Tablet, Chlopro 100mg Tablet |
25-100 mg orally or intramuscularly every 4-6 hours; maximum 2 g/day orally or 1 g/day intramuscularly.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment necessary for GFR ≥10 mL/min; for GFR <10 mL/min, administer 75% of normal dose at same intervals. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduced dose should be individualized; use with caution. |
| Pediatric use | 0.5-1 mg/kg orally or intramuscularly every 4-6 hours; maximum daily dose 100 mg for <5 years, 200 mg for 5-12 years, 500 mg for >12 years. |
| Geriatric use | Initiate at 10-25 mg orally once daily; increase slowly to minimum effective dose; maximum 200 mg/day; monitor for hypotension and sedation. |
| 1st trimester | Avoid in first trimester unless essential; risk of congenital malformations, particularly neural tube defects and cardiovascular anomalies, based on human data. |
| 2nd trimester | Use only if clearly needed; potential for maternal hypotension and fetal hypoxia. Monitor for neonatal effects. |
| 3rd trimester | Avoid near term; risk of maternal hypotension, neonatal respiratory depression, extrapyramidal symptoms, and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).
| Placental transfer | Chlorpromazine readily crosses the placenta; fetal serum concentrations are approximately 50-70% of maternal levels. |
| Breastfeeding | Chlorpromazine is excreted into breast milk in low concentrations. Monitor infant for sedation, poor feeding, and extrapyramidal reactions. The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised, especially in preterm or ill infants. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Not approved for the treatment of dementia-related psychosis.
| Serious Effects |
ComaSevere CNS depressionBone marrow suppressionPheochromocytomaHypersensitivity to phenothiazinesSubcortical brain damage
| Precautions | Tardive dyskinesia, Neuroleptic malignant syndrome, QT prolongation and sudden cardiac death, Leukopenia/neutropenia/agranulocytosis, Seizures (lower threshold), Orthostatic hypotension, Increased risk of falls due to sedation and hypotension, Anticholinergic effects (dry mouth, constipation, blurred vision) |
| Food/Dietary | Avoid excessive caffeine as it may exacerbate anxiety or agitation. Grapefruit juice may increase chlorpromazine levels; limit or avoid concurrent intake. Tyramine-rich foods (aged cheeses, cured meats) have no well-established interaction but caution is advised due to potential blood pressure effects. Maintain adequate hydration to counteract anticholinergic effects. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Limited data suggest a small increased risk of congenital malformations, particularly neural tube defects and limb anomalies, based on retrospective studies. Second and third trimesters: Chronic use may lead to neonatal extrapyramidal symptoms, jaundice, and CNS depression; neonatal withdrawal syndrome reported. Risk of maternal hypotension and decreased placental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure, extrapyramidal symptoms, and mental status. Fetal monitoring: assess growth and development, particularly if chronic therapy. Neonatal monitoring: watch for extrapyramidal signs, jaundice, and respiratory depression after delivery. |
| Fertility Effects | May cause hyperprolactinemia due to dopamine blockade, leading to menstrual irregularities, anovulation, galactorrhea, and reduced fertility. Effects are reversible upon dose reduction or discontinuation. |
| Clinical Pearls | Chlorpromazine is a low-potency typical antipsychotic with strong anticholinergic and alpha-adrenergic blocking effects. Use with caution in elderly patients due to increased risk of falls, orthostatic hypotension, and anticholinergic adverse effects. Monitor for QTc prolongation and extrapyramidal symptoms, though EPS risk is lower than with high-potency agents. May lower seizure threshold. Can cause photosensitivity; advise sun protection. Depot formulations exist, but oral is more common. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly without consulting your doctor. · Avoid alcohol and other CNS depressants as they can increase sedation and dizziness. · Rise slowly from sitting or lying positions to prevent falls due to low blood pressure. · Use sunscreen and protective clothing to prevent severe sunburn. · Report any uncontrolled muscle movements, restlessness, or stiffness. · May cause drowsiness; avoid driving or operating heavy machinery until you know how the drug affects you. · Dry mouth can be managed with sugarless gum or candy; if persistent, inform your doctor. · Do not take with other medications without approval, especially those affecting heart rhythm. |