PROCHLORPERAZINE
Clinical safety rating: safe
Animal studies have demonstrated safety
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.
| 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. |
| Molecular Weight | 373.92 |
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. |
| 1st trimester | Limited human data; animal studies show increased risk of skeletal anomalies at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | May cause extrapyramidal symptoms in neonate if used near term. Monitor for maternal hypotension. |
| 3rd trimester | Avoid in last weeks due to risk of neonatal extrapyramidal effects, jaundice, and prolonged QT interval. |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| Placental transfer | Passes placenta; detected in cord blood. Fetal levels approximately 50% of maternal. |
| Breastfeeding | Prochlorperazine is excreted into breast milk in low amounts. Monitor infant for drowsiness, irritability, or feeding difficulties. American Academy of Pediatrics considers compatible with breastfeeding, but caution advised. |
■ 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.
| Common Effects | nausea/vomiting |
| Serious Effects |
Hypersensitivity to prochlorperazine or other phenothiazinesCNS depression (e.g., coma, barbiturate or alcohol intoxication)Bone marrow suppressionPheochromocytomaConcomitant use with high-dose CNS depressantsHistory of tardive dyskinesia
| 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. |
| Food/Dietary |
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| Lactation Rating | L3 - Limited data (probably compatible) |
| 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. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, ECG (especially if other QT-prolonging drugs), extrapyramidal symptoms, sedation, CBC with prolonged use. Fetal/neonatal: Monitor for neonatal depression, extrapyramidal signs, jaundice, and QT prolongation if exposure near term. |
| Fertility Effects | May cause hyperprolactinemia, which can inhibit ovulation and reduce fertility. Reversible upon discontinuation. Use in men can cause sexual dysfunction (e.g., impotence, gynecomastia). |
| No significant food interactions. Avoid alcohol. Grapefruit juice has not been reported to interact significantly, but caution advised due to potential QT prolongation. |
| Clinical Pearls | Prochlorperazine is a phenothiazine antipsychotic with strong antiemetic properties. It can cause extrapyramidal symptoms (EPS), especially in young adults and elderly. Use with caution in patients with Parkinson's disease. May prolong QTc interval; avoid in patients with electrolyte disturbances or concomitant QT-prolonging drugs. Neurologic malignant syndrome (NMS) is rare but life-threatening. For acute dystonia, treat with diphenhydramine or benztropine intravenously. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · May cause drowsiness or dizziness; do not drive or operate heavy machinery until you know how this medication affects you. · Rise slowly from sitting or lying positions to avoid dizziness. · Avoid alcohol and other central nervous system depressants. · Report any unusual muscle movements, stiffness, fever, or confusion to your healthcare provider immediately. · May increase sensitivity to sunlight; use sunscreen and protective clothing outdoors. · Do not stop taking abruptly without medical advice. |