PROCHLORPERAZINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Prochlorperazine is a phenothiazine antipsychotic that acts as a dopamine D2 receptor antagonist in the chemoreceptor trigger zone (CTZ) and at high doses in the mesolimbic system. It also has anticholinergic and antiemetic effects.

What the body does with it

Metabolism	Primarily metabolized via CYP2D6 and other CYP450 isoenzymes. Active metabolites include prochlorperazine sulfoxide, N-desmethylprochlorperazine, and others.
Excretion	Renal: 70-80% (as metabolites), Fecal: 20-30% (unchanged and metabolites), Biliary: 10-15% of dose excreted in bile.
Half-life	Terminal elimination half-life: 23-25 hours, with prolonged elimination in hepatic impairment.
Protein binding	91-93% bound, primarily to albumin.
Volume of Distribution	12.9-17.5 L/kg, indicating extensive tissue distribution and penetration into CSF.
Bioavailability	Oral: 50-60% (due to first-pass metabolism); Intramuscular: 100%; Rectal: 80-90% (compared to IM).
Onset of Action	Oral: 30-60 minutes; Intramuscular: 10-20 minutes; Intravenous: 1-5 minutes; Rectal: 15-30 minutes.
Duration of Action	Oral: 4-6 hours; Intramuscular: 4-6 hours; Intravenous: 3-4 hours; Rectal: 4-6 hours. Antiemetic effect may persist longer.

Classification & Brands

Dosing & administration

5-10 mg IM/IV every 3-4 hours as needed; or 5-10 mg PO 3-4 times daily; or 25 mg PR twice daily. Maximum IM/IV: 40 mg/day; PO: 40 mg/day.

Dosage form	SUPPOSITORY
Renal impairment	No specific dose adjustment required for renal impairment. Use with caution in severe renal impairment due to potential accumulation of metabolites.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment (Child-Pugh A or B), reduce dose by 50% and monitor for adverse effects.
Pediatric use	Children >2 years and >10 kg: Nausea/vomiting: 0.1-0.15 mg/kg/dose IM/IV every 3-4 hours; or 0.4 mg/kg/day PO divided 3-4 times daily. Maximum: 20 mg/day for <5 years, 25 mg/day for 5-12 years.
Geriatric use	Initiate at lower doses (e.g., 2.5-5 mg PO once or twice daily) due to increased sensitivity to extrapyramidal effects and orthostatic hypotension. Maximum: 20 mg/day.

Use during pregnancy

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

Clinical note

CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.

Breastfeeding	Prochlorperazine is excreted into breast milk in low amounts; M/P ratio not well established. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for drowsiness or extrapyramidal effects. Weigh risk vs benefit, especially in neonates or preterm infants.
Teratogenic Risk	First trimester: Limited human data; animal studies show fetal resorption at high doses. Not considered a major teratogen; however, risk-benefit should be assessed. Second/third trimester: Use near term may cause extrapyramidal symptoms and/or withdrawal in neonates (e.g., hypertonicity, tremor). Cases of neonatal jaundice and prolonged QT have been reported.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; drug is not approved for this condition. Cases of tardive dyskinesia (TD) may develop. Neuroleptic malignant syndrome (NMS) reported.

Side Effect Profile

Common Effects	nausea/vomiting
Serious Effects

Absolute Contraindications

Hypersensitivity to prochlorperazine or other phenothiazines; comatose states or CNS depression; bone marrow suppression; severe liver disease; concurrent use with large amounts of ethanol or other depressants; children <2 years or weight <9 kg; suspected Reye's syndrome in children.

Clinical Precautions

Precautions

Potential for QT prolongation, seizures, jaundice, leukopenia, agranulocytosis, and photosensitivity. Use with caution in patients with bone marrow suppression, severe liver or renal impairment, Parkinson's disease, and CNS depression.

Clinical Tips & Counseling

Drug interactions

Loading safety data…