PROCHLORPERAZINE MALEATE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
Prochlorperazine is a phenothiazine antipsychotic that primarily antagonizes dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) and central nervous system. It also has anticholinergic and antiemetic effects through blockade of histamine H1 and muscarinic M1 receptors.
| Metabolism | Primarily hepatic via CYP2D6 and to a lesser extent CYP3A4, with glucuronidation. Active metabolites include N-desmethylprochlorperazine. |
| Excretion | Primarily renal (70-80% as metabolites, <1% unchanged); fecal/biliary excretion accounts for 20-30% via enterohepatic circulation. |
| Half-life | Terminal elimination half-life is approximately 6-8 hours in adults, but may extend up to 12-15 hours after chronic dosing or in hepatic impairment. |
| Protein binding | 90-95% bound, primarily to albumin. |
| Volume of Distribution | 12-20 L/kg (large, indicates extensive tissue distribution and crossing of blood-brain barrier). |
| Bioavailability | Oral: ~60% (due to first-pass metabolism); IM: ~90%; Rectal: ~70%; IV: 100%. |
| Onset of Action | Oral: 30-40 minutes; IM: 10-20 minutes; IV: 5-10 minutes; Rectal: 60-90 minutes. |
| Duration of Action | Oral/IM: 3-4 hours (antiemetic); up to 12 hours (antipsychotic) with repeated dosing; IV: 2-3 hours. |
5-10 mg orally 3-4 times daily; or 25 mg rectally twice daily; or 5-10 mg intramuscularly every 3-4 hours up to 40 mg/day; or 2.5-10 mg intravenously slowly at 2.5 mg/min, maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment required; caution in severe renal impairment due to potential accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Weight >10 kg: 0.4 mg/kg/day orally or rectally in 3-4 divided doses; or 0.4 mg/kg/day IM in 3-4 divided doses, maximum 20 mg/day for adolescents. |
| Geriatric use | Initiate at 5 mg orally once or twice daily; increase gradually; avoid in dementia with behavioral disturbances due to increased risk of stroke and mortality. |
| 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.
| FDA category | Animal |
| Breastfeeding | Prochlorperazine is excreted into breast milk in low amounts; M/P ratio approximately 0.34. Limited data suggest low risk to infant at usual maternal doses; however, monitor for drowsiness or extrapyramidal effects. A decision should be made to discontinue breastfeeding or the drug, considering importance to mother. |
| Teratogenic Risk |
■ 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.
| Common Effects | nausea/vomiting |
| Serious Effects |
["Comatose states","CNS depression (e.g., alcohol, barbiturates)","Pheochromocytoma","Bone marrow depression","Pediatric surgery (use in children <2 years or <9 kg)","Hypersensitivity to prochlorperazine or other phenothiazines"]
| Precautions | ["Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","QT prolongation and arrhythmias","Extrapyramidal symptoms (EPS)","Agranulocytosis, leukopenia, neutropenia","Seizures","Antiemetic masking of other conditions"] |
Loading safety data…
| First trimester: Limited human data suggest a possible small increased risk of congenital malformations, particularly with high doses; animal studies have shown embryotoxicity at high doses. Second and third trimesters: Risk of extrapyramidal symptoms and withdrawal in neonates after exposure during late pregnancy; avoid use near term. |
| Fetal Monitoring | Monitor maternal blood pressure, especially during IV use; observe for maternal extrapyramidal symptoms. In neonates exposed in utero during third trimester, monitor for transient extrapyramidal signs, respiratory distress, and feeding difficulties. |
| Fertility Effects | May cause hyperprolactinemia which can inhibit ovulation or impair spermatogenesis; reversible upon discontinuation. In animals, high doses have shown reduced fertility; human data limited. |