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. |
| Molecular Weight | 606.09 |
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 | Avoid in first trimester unless benefit outweighs risk; associated with malformations in animal studies but human data limited. |
| 2nd trimester | Use only if clearly needed; monitor for extrapyramidal symptoms and maternal hypotension. |
| 3rd trimester | Avoid near term; may cause neonatal extrapyramidal symptoms, jaundice, and prolonged QT interval. |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| FDA category | Animal |
| Placental transfer | Crosses placenta; detectable in fetal plasma with levels 25-50% of maternal levels. |
| Breastfeeding |
■ 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 statesCNS depressionPheochromocytomaBone marrow suppressionHypersensitivity to prochlorperazine or phenothiazinesPediatric surgery (increased risk of extrapyramidal symptoms)QT interval prolongation or concurrent QT-prolonging drugs
| Precautions | Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, QT prolongation and arrhythmias, Extrapyramidal symptoms (EPS), Agranulocytosis, leukopenia, neutropenia, Seizures, Antiemetic masking of other conditions |
| Food/Dietary | Avoid alcohol and CNS depressants. High-fat meals may increase absorption. No specific food restrictions; maintain adequate hydration. |
Loading safety data…
| Excreted into breast milk in low concentrations; monitor infant for drowsiness, irritability, and extrapyramidal symptoms; use caution. |
| Lactation Rating | L3 (Moderately Safe) - limited data, consider risk/benefit. |
| Teratogenic Risk | 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. |
| Clinical Pearls | Prochlorperazine maleate is a phenothiazine antiemetic and antipsychotic. For acute nausea/vomiting, IM or IV routes provide rapid onset; avoid SC due to irritation. Monitor for extrapyramidal symptoms (EPS), especially in young adults and elderly. QT prolongation risk; avoid concurrent use with other QT-prolonging agents. May cause orthostatic hypotension; advise patients to rise slowly. Use lowest effective dose for shortest duration in elderly due to increased sensitivity and anticholinergic effects. |
| Patient Advice | Take exactly as prescribed; do not exceed dose. · Avoid alcohol and CNS depressants. · May cause drowsiness or dizziness; avoid driving until you know how you react. · Change positions slowly to prevent fainting. · Report uncontrolled muscle movements, fever, or irregular heartbeat. · Use sun protection; may increase sensitivity to sunlight. · Do not stop suddenly; taper under doctor's guidance. |