COMPRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COMPRO (COMPRO).

How it works

Prochlorperazine is a phenothiazine antipsychotic that primarily acts as a dopamine D2 receptor antagonist, with additional antagonism at D3, 5-HT2A, alpha1-adrenergic, and histamine H1 receptors. It also has antiemetic effects via D2 blockade in the chemoreceptor trigger zone.

What the body does with it

Metabolism	Primarily hepatic via CYP2D6, with minor contributions from CYP1A2 and CYP3A4. Prochlorperazine is extensively metabolized by oxidation, N-demethylation, and sulfoxidation.
Excretion	Renal: 70-80% as glucuronide and sulfate conjugates; biliary/fecal: <10% unchanged; <5% as unchanged drug in urine.
Half-life	Terminal elimination half-life: 4-6 hours in adults (prolonged in hepatic impairment, cirrhosis up to 10-12 hours; neonates up to 24 hours).
Protein binding	85-95% bound to alpha1-acid glycoprotein, albumin, and lipoproteins.
Volume of Distribution	Vd: 4-7 L/kg (large, indicating extensive tissue distribution; crosses blood-brain barrier and placenta).
Bioavailability	Oral: 80-95% (first-pass metabolism ~20-30%); IM: 90-100%; Rectal: 60-80% (variable).
Onset of Action	Oral: 30-60 minutes; IM: 10-20 minutes; IV: 2-5 minutes; Rectal: 20-60 minutes.
Duration of Action	Oral/rectal: 4-6 hours; IM: 4-6 hours; IV: 2-4 hours. Clinical notes: Duration may be shorter in children due to faster metabolism.

Classification & Brands

Dosing & administration

5 to 10 mg intramuscularly every 3 to 4 hours as needed; or 5 to 10 mg intravenously at a rate not exceeding 5 mg per minute; or 10 mg orally every 6 to 8 hours; maximum daily dose 40 mg.

Dosage form	SUPPOSITORY
Renal impairment	No specific dose adjustment recommended; use with caution in severe renal impairment.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment, consider dose reduction and monitor closely.
Pediatric use	Children 2 years and older: 0.1 to 0.15 mg/kg intramuscularly every 6 to 8 hours; maximum 10 mg per dose. Oral: 0.5 mg/kg/day in divided doses every 6 to 8 hours. Not recommended in children under 2 years.
Geriatric use	Initiate at lower doses (e.g., 5 mg orally or intramuscularly) with cautious titration due to increased sensitivity; monitor for hypotension and extrapyramidal symptoms.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for COMPRO (COMPRO).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Potential for adverse effects in infant (drowsiness, extrapyramidal signs). Avoid breastfeeding or use with caution, monitor infant for sedation and motor abnormalities.
Teratogenic Risk	COMPRO (prochlorperazine) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies suggest risk of skeletal malformations and cleft palate at high doses. Second and third trimesters: Risk of extrapyramidal signs and neonatal withdrawal if used near term. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Prochlorperazine is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to prochlorperazine or other phenothiazines","Comatose states or severe CNS depression","Pediatric surgery (in children less than 2 years or weighing less than 9 kg)","Pediatric surgery in children with conditions causing Reye's syndrome","Use in children with suspected Reye's syndrome"]

Clinical Precautions

Precautions

["May cause tardive dyskinesia, a potentially irreversible syndrome of involuntary dyskinetic movements","May cause neuroleptic malignant syndrome (NMS), a potentially fatal symptom complex","May cause extrapyramidal symptoms (EPS), including acute dystonia, parkinsonism, and akathisia","May cause sedation, drowsiness, and impaired mental/physical abilities","May lower seizure threshold","May cause orthostatic hypotension","May cause leukopenia, neutropenia, and agranulocytosis","May prolong QT interval and cause cardiac arrhythmias","May cause hyperprolactinemia"]

Clinical Tips & Counseling

Drug interactions

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COMPRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COMPRO (COMPRO).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP2D6, with minor contributions from CYP1A2 and CYP3A4. Prochlorperazine is extensively metabolized by oxidation, N-demethylation, and sulfoxidation.
Excretion	Renal: 70-80% as glucuronide and sulfate conjugates; biliary/fecal: <10% unchanged; <5% as unchanged drug in urine.
Half-life	Terminal elimination half-life: 4-6 hours in adults (prolonged in hepatic impairment, cirrhosis up to 10-12 hours; neonates up to 24 hours).
Protein binding	85-95% bound to alpha1-acid glycoprotein, albumin, and lipoproteins.
Volume of Distribution	Vd: 4-7 L/kg (large, indicating extensive tissue distribution; crosses blood-brain barrier and placenta).
Bioavailability	Oral: 80-95% (first-pass metabolism ~20-30%); IM: 90-100%; Rectal: 60-80% (variable).
Onset of Action	Oral: 30-60 minutes; IM: 10-20 minutes; IV: 2-5 minutes; Rectal: 20-60 minutes.
Duration of Action	Oral/rectal: 4-6 hours; IM: 4-6 hours; IV: 2-4 hours. Clinical notes: Duration may be shorter in children due to faster metabolism.

Classification & Brands

Dosing & administration

5 to 10 mg intramuscularly every 3 to 4 hours as needed; or 5 to 10 mg intravenously at a rate not exceeding 5 mg per minute; or 10 mg orally every 6 to 8 hours; maximum daily dose 40 mg.

Dosage form	SUPPOSITORY
Renal impairment	No specific dose adjustment recommended; use with caution in severe renal impairment.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment, consider dose reduction and monitor closely.
Pediatric use	Children 2 years and older: 0.1 to 0.15 mg/kg intramuscularly every 6 to 8 hours; maximum 10 mg per dose. Oral: 0.5 mg/kg/day in divided doses every 6 to 8 hours. Not recommended in children under 2 years.
Geriatric use	Initiate at lower doses (e.g., 5 mg orally or intramuscularly) with cautious titration due to increased sensitivity; monitor for hypotension and extrapyramidal symptoms.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for COMPRO (COMPRO).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Potential for adverse effects in infant (drowsiness, extrapyramidal signs). Avoid breastfeeding or use with caution, monitor infant for sedation and motor abnormalities.
Teratogenic Risk	COMPRO (prochlorperazine) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies suggest risk of skeletal malformations and cleft palate at high doses. Second and third trimesters: Risk of extrapyramidal signs and neonatal withdrawal if used near term. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Prochlorperazine is not approved for the treatment of dementia-related psychosis.