CHLORPROMAZINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).

How it works

Antagonizes dopamine D2 receptors in the mesolimbic pathway; also blocks alpha-adrenergic, histamine H1, muscarinic, and serotonin receptors.

What the body does with it

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.

Classification & Brands

Action Class	Typical Antipsychotics
Brand Substitutes	Clozine 100mg Tablet, Prozine 100mg Tablet, Sun Prazin 100mg Tablet, Zinetil 100mg Tablet, Chlopro 100mg Tablet

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).

Breastfeeding	Excreted in breast milk; M/P ratio approximately 0.5. Infant exposure is low but may cause sedation, irritability, and poor feeding. Use with caution, monitor infant for adverse effects; consider alternative agents if high maternal doses required.
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.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis. Not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","CNS depression (alcohol, barbiturates, opioids)","Known hypersensitivity to chlorpromazine","Concurrent use with high doses of CNS depressants","Pediatric patients with conditions such as Reye's syndrome or recent head trauma (relative)","Severe bone marrow suppression (relative)"]

Clinical Precautions

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)"]

Clinical Tips & Counseling

Drug interactions

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CHLORPROMAZINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).

How it works

Antagonizes dopamine D2 receptors in the mesolimbic pathway; also blocks alpha-adrenergic, histamine H1, muscarinic, and serotonin receptors.

What the body does with it

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.

Classification & Brands

Action Class	Typical Antipsychotics
Brand Substitutes	Clozine 100mg Tablet, Prozine 100mg Tablet, Sun Prazin 100mg Tablet, Zinetil 100mg Tablet, Chlopro 100mg Tablet

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CHLORPROMAZINE HYDROCHLORIDE (CHLORPROMAZINE HYDROCHLORIDE).

Breastfeeding	Excreted in breast milk; M/P ratio approximately 0.5. Infant exposure is low but may cause sedation, irritability, and poor feeding. Use with caution, monitor infant for adverse effects; consider alternative agents if high maternal doses required.
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.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis. Not approved for the treatment of dementia-related psychosis.