COMPAZINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COMPAZINE (COMPAZINE).

How it works

Dopamine D2 receptor antagonist in the chemoreceptor trigger zone; also blocks alpha-1 adrenergic, histamine H1, and muscarinic M1 receptors.

What the body does with it

Metabolism	Primarily hepatic via CYP2D6; also involves CYP3A4 and flavin-containing monooxygenase (FMO3).
Excretion	Renal (approximately 70% as metabolites, <1% unchanged), biliary/fecal (approximately 30%).
Half-life	Terminal elimination half-life is approximately 23 hours (range 15-30 hours) after oral or intramuscular administration. Clinical context: requires multiple daily dosing for steady state.
Protein binding	Approximately 91-99% bound, primarily to albumin.
Volume of Distribution	Approximately 12-15 L/kg. Large Vd indicates extensive tissue distribution, including penetration into the CNS.
Bioavailability	Oral: approximately 30% due to first-pass metabolism; Intramuscular: approximately 100%; Rectal: approximately 70-80%.
Onset of Action	Oral: 30-40 minutes; Intramuscular: 10-20 minutes; Intravenous: 1-5 minutes; Rectal: 30-60 minutes.
Duration of Action	Oral: 3-4 hours; Intramuscular: 3-4 hours; Intravenous: 1-2 hours; Rectal: 3-4 hours. Extended use may lead to tolerance.

Classification & Brands

Dosing & administration

5-10 mg IM/IV every 3-4 hours as needed; or 25 mg PO/PR twice daily for severe nausea/vomiting.

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <10 mL/min) due to increased risk of sedation and hypotension.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or use 25% of normal dose.
Pediatric use	0.1-0.15 mg/kg/dose PO/IM/IV every 4-6 hours as needed; maximum 10 mg/day for <5 years, 15 mg/day for 5-12 years.
Geriatric use	Initiate at lowest effective dose (2.5 mg PO/PR or IM); titrate cautiously due to increased sensitivity to extrapyramidal effects, orthostatic 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 COMPAZINE (COMPAZINE).

Breastfeeding	Prochlorperazine is excreted into breast milk. The milk-to-plasma ratio is approximately 1.0. Limited data suggest low infant doses (<1% of maternal weight-adjusted dose). However, potential adverse effects include drowsiness and extrapyramidal symptoms. Caution is advised; monitor infant for sedation, irritability, and motor abnormalities.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: No adequate studies; potential risk based on animal data (cleft palate, skeletal anomalies). Second/third trimesters: Risk of extrapyramidal symptoms and neonatal withdrawal with chronic use. Avoid use near term due to risk of maternal hypotension and neonatal respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of death in elderly patients with dementia-related psychosis, similar to other antipsychotics.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","CNS depression (alcohol, barbiturates, opioids)","Bone marrow suppression","Pheochromocytoma","Pediatric surgery or children <2 years","Hypersensitivity to phenothiazines"]

Clinical Precautions

Precautions

["Tardive dyskinesia","Neuroleptic malignant syndrome","Extrapyramidal symptoms","Falls and fractures in elderly","Bone marrow suppression","QT prolongation","Hepatic impairment"]

Clinical Tips & Counseling

Drug interactions

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COMPAZINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COMPAZINE (COMPAZINE).

How it works

Dopamine D2 receptor antagonist in the chemoreceptor trigger zone; also blocks alpha-1 adrenergic, histamine H1, and muscarinic M1 receptors.

What the body does with it

Metabolism	Primarily hepatic via CYP2D6; also involves CYP3A4 and flavin-containing monooxygenase (FMO3).
Excretion	Renal (approximately 70% as metabolites, <1% unchanged), biliary/fecal (approximately 30%).
Half-life	Terminal elimination half-life is approximately 23 hours (range 15-30 hours) after oral or intramuscular administration. Clinical context: requires multiple daily dosing for steady state.
Protein binding	Approximately 91-99% bound, primarily to albumin.
Volume of Distribution	Approximately 12-15 L/kg. Large Vd indicates extensive tissue distribution, including penetration into the CNS.
Bioavailability	Oral: approximately 30% due to first-pass metabolism; Intramuscular: approximately 100%; Rectal: approximately 70-80%.
Onset of Action	Oral: 30-40 minutes; Intramuscular: 10-20 minutes; Intravenous: 1-5 minutes; Rectal: 30-60 minutes.
Duration of Action	Oral: 3-4 hours; Intramuscular: 3-4 hours; Intravenous: 1-2 hours; Rectal: 3-4 hours. Extended use may lead to tolerance.

Classification & Brands

Dosing & administration

5-10 mg IM/IV every 3-4 hours as needed; or 25 mg PO/PR twice daily for severe nausea/vomiting.

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <10 mL/min) due to increased risk of sedation and hypotension.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or use 25% of normal dose.
Pediatric use	0.1-0.15 mg/kg/dose PO/IM/IV every 4-6 hours as needed; maximum 10 mg/day for <5 years, 15 mg/day for 5-12 years.
Geriatric use	Initiate at lowest effective dose (2.5 mg PO/PR or IM); titrate cautiously due to increased sensitivity to extrapyramidal effects, orthostatic 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 COMPAZINE (COMPAZINE).

Breastfeeding	Prochlorperazine is excreted into breast milk. The milk-to-plasma ratio is approximately 1.0. Limited data suggest low infant doses (<1% of maternal weight-adjusted dose). However, potential adverse effects include drowsiness and extrapyramidal symptoms. Caution is advised; monitor infant for sedation, irritability, and motor abnormalities.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: No adequate studies; potential risk based on animal data (cleft palate, skeletal anomalies). Second/third trimesters: Risk of extrapyramidal symptoms and neonatal withdrawal with chronic use. Avoid use near term due to risk of maternal hypotension and neonatal respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of death in elderly patients with dementia-related psychosis, similar to other antipsychotics.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","CNS depression (alcohol, barbiturates, opioids)","Bone marrow suppression","Pheochromocytoma","Pediatric surgery or children <2 years","Hypersensitivity to phenothiazines"]

Clinical Precautions

Precautions

["Tardive dyskinesia","Neuroleptic malignant syndrome","Extrapyramidal symptoms","Falls and fractures in elderly","Bone marrow suppression","QT prolongation","Hepatic impairment"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…