PROCHLORPERAZINE EDISYLATE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
Prochlorperazine is a phenothiazine antipsychotic that antagonizes dopamine D2 receptors in the brain, particularly in the chemoreceptor trigger zone, exerting antiemetic effects. It also blocks alpha-adrenergic and muscarinic receptors.
| Metabolism | Primarily hepatic via CYP2D6 and other CYP450 enzymes; sulfoxide and N-demethylated metabolites. |
| Excretion | Primarily renal excretion of metabolites (approximately 70-80% as conjugated metabolites), with less than 1% excreted unchanged. Fecal excretion accounts for about 20-30% via biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 6-8 hours, but may be prolonged to 10-12 hours in elderly patients or those with hepatic impairment. In overdoses, half-life can extend beyond 24 hours. |
| Protein binding | 90-99% bound primarily to albumin. Binding is highly variable and may be decreased in hepatic disease. |
| Volume of Distribution | Approximately 12-20 L/kg (1250-2000 L in a 70 kg adult). Large Vd indicates extensive tissue distribution and accumulation in brain tissue. |
| Bioavailability | Oral: approximately 30-50% due to first-pass metabolism (range 20-70% interindividual variability). Intramuscular: 100% (complete absorption). Rectal: approximately 50-70%. |
| Onset of Action | Oral: 30-40 minutes; Intramuscular: 10-20 minutes; Intravenous: 5-10 minutes; Rectal: 30-60 minutes. |
| Duration of Action | Antiemetic effect lasts 3-4 hours after oral or intramuscular administration, and 6-8 hours after intravenous administration. For antipsychotic effects (higher doses), duration may be up to 12-24 hours. |
Antiemetic: 5-10 mg IM/IV every 3-4 hours as needed, maximum 40 mg/day; or 25 mg PR twice daily. Antipsychotic: 10-20 mg IM/IV every 1-4 hours, maximum 40 mg/day; oral: 5-10 mg 3-4 times daily, maximum 150 mg/day.
| Dosage form | SYRUP |
| Renal impairment | No specific dose adjustment provided; use caution in severe renal impairment (CrCl <10 mL/min) due to potential for accumulation. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 50%; Child-Pugh C: Avoid use or use with extreme caution, consider alternative. |
| Pediatric use | Antiemetic: >2 years and >9 kg: 0.1-0.15 mg/kg IM/IV every 3-4 hours as needed, maximum 10 mg/day; oral/PR: 2.5 mg 2-3 times daily or 5 mg twice daily, maximum 15 mg/day. Antipsychotic: >2 years: 0.1 mg/kg/dose IM/IV every 6-8 hours, maximum 20 mg/day. |
| Geriatric use | Use lowest effective dose; initial dose 2.5-5 mg IM/PO/PR; increase cautiously; monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. Consider renal and hepatic function. |
| 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 | Excreted into breast milk in low amounts; M/P ratio not established. Use with caution due to potential for EPS and sedation in infants. Manufacturer advises avoiding breastfeeding during therapy. |
| Teratogenic Risk | First trimester: Limited data; potential for increased risk of neural tube defects and cardiovascular anomalies from animal studies; human data insufficient to quantify risk. Second and third trimesters: Possible association with fetal extrapyramidal symptoms (EPS) and neonatal withdrawal if used near term. Avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Not approved for dementia-related psychosis.
| Common Effects | nausea/vomiting |
| Serious Effects |
Comatose states, CNS depression, concurrent use of high doses of CNS depressants, pheochromocytoma, severe hepatic or renal impairment, history of blood dyscrasias, hypersensitivity to any phenothiazine.
| Precautions | QT prolongation, tardive dyskinesia, neuroleptic malignant syndrome (NMS), extrapyramidal symptoms (EPS), orthostatic hypotension, cholestatic jaundice, agranulocytosis, seizures, and photosensitivity. Avoid in patients with bone marrow depression or severe hypotension. |
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| Fetal Monitoring | Monitor for maternal EPS, hypotension, and neuroleptic malignant syndrome (NMS). Fetal monitoring for heart rate variability and growth restriction if used chronically. Neonatal monitoring for EPS, sedation, and withdrawal symptoms after delivery. |
| Fertility Effects | May cause hyperprolactinemia leading to menstrual irregularities, anovulation, and reduced fertility. Reversible upon discontinuation. |