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. |
| Molecular Weight | 414 |
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 | Avoid if possible; limited data suggest increased risk of congenital malformations?; use only if maternal benefit outweighs potential fetal risk. |
| 2nd trimester | Use with caution; no well-documented teratogenicity; monitor for maternal hypotension and fetal effects. |
| 3rd trimester | Avoid near term; may cause extrapyramidal reactions, respiratory depression, or withdrawal symptoms in neonate; use only if clearly needed. |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| FDA category | Animal |
| Placental transfer | Crosses placenta; detected in cord blood and amniotic fluid; limited quantitative data. |
| Breastfeeding |
■ 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 statesCNS depression (e.g., from alcohol or depressants)Hypersensitivity to prochlorperazine or phenothiazinesPediatric surgery (contraindicated for pediatric outpatient surgery in some regions)
| 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. |
| Food/Dietary | No specific food interactions are documented. However, grapefruit juice may theoretically inhibit CYP2D6 metabolism, leading to increased prochlorperazine levels; caution is advised. Avoid excessive caffeine as it may worsen side effects like restlessness. Take with food if GI upset occurs. Avoid alcohol. |
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| Excreted into breast milk in small amounts; potential for infant sedation and extrapyramidal effects; consider alternative if infant is young or high dose maternal use. |
| Lactation Rating | L3 - Limited Data |
| 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. |
| 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. |
| Clinical Pearls | Prochlorperazine edisylate is a piperazine phenothiazine used primarily as an antiemetic but also has antipsychotic properties. It is more potent than chlorpromazine. Extrapyramidal symptoms (EPS) are dose-dependent and more common in children and young adults. Monitor for QT prolongation, especially at high doses or with IV use. Avoid in patients with CNS depression, bone marrow suppression, or severe hypotension. Can cause neuroleptic malignant syndrome (NMS), though less common. The edisylate salt is water-soluble; available in oral, IM, and IV formulations. Antiemetic doses are typically lower than antipsychotic doses. |
| Patient Advice | Take exactly as prescribed; do not increase dose without consulting your doctor. · May cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how this medication affects you. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they can increase sedation. · Rise slowly from a sitting or lying position to minimize dizziness from low blood pressure. · Contact your doctor immediately if you experience fever, muscle stiffness, confusion, irregular heartbeat, or uncontrolled muscle movements. · Report any signs of infection (fever, sore throat) or easy bruising/bleeding. · Avoid prolonged sun exposure; use sunscreen and wear protective clothing as this drug can increase sun sensitivity. · Do not stop abruptly without medical advice; gradual discontinuation may be needed. |