COMPAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COMPAZINE (COMPAZINE).
Dopamine D2 receptor antagonist in the chemoreceptor trigger zone; also blocks alpha-1 adrenergic, histamine H1, and muscarinic M1 receptors.
| Metabolism | Primarily hepatic via CYP2D6; also involves CYP3A4 and flavin-containing monooxygenase (FMO3). |
| Excretion | Renal (approximately 70% as metabolites, <1% unchanged), biliary/fecal (approximately 30%). |
| Half-life | Terminal elimination half-life is approximately 23 hours (range 15-30 hours) after oral or intramuscular administration. Clinical context: requires multiple daily dosing for steady state. |
| Protein binding | Approximately 91-99% bound, primarily to albumin. |
| Volume of Distribution | Approximately 12-15 L/kg. Large Vd indicates extensive tissue distribution, including penetration into the CNS. |
| Bioavailability | Oral: approximately 30% due to first-pass metabolism; Intramuscular: approximately 100%; Rectal: approximately 70-80%. |
| Onset of Action | Oral: 30-40 minutes; Intramuscular: 10-20 minutes; Intravenous: 1-5 minutes; Rectal: 30-60 minutes. |
| Duration of Action | Oral: 3-4 hours; Intramuscular: 3-4 hours; Intravenous: 1-2 hours; Rectal: 3-4 hours. Extended use may lead to tolerance. |
| Molecular Weight | 373.94 |
5-10 mg IM/IV every 3-4 hours as needed; or 25 mg PO/PR twice daily for severe nausea/vomiting.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <10 mL/min) due to increased risk of sedation and hypotension. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or use 25% of normal dose. |
| Pediatric use | 0.1-0.15 mg/kg/dose PO/IM/IV every 4-6 hours as needed; maximum 10 mg/day for <5 years, 15 mg/day for 5-12 years. |
| Geriatric use | Initiate at lowest effective dose (2.5 mg PO/PR or IM); titrate cautiously due to increased sensitivity to extrapyramidal effects, orthostatic hypotension, and sedation. |
| 1st trimester | Avoid due to risk of teratogenicity; prochlorperazine is not recommended in first trimester unless absolutely necessary. |
| 2nd trimester | Use only if clearly needed; may cause extrapyramidal effects in neonate if used near term. |
| 3rd trimester | Avoid near term; risk of neonatal extrapyramidal symptoms, jaundice, and prolonged QT interval. |
Clinical note
Comprehensive clinical and safety monograph for COMPAZINE (COMPAZINE).
| Placental transfer | Crosses placenta; fetal concentrations may be similar to maternal levels. |
| Breastfeeding | Prochlorperazine is excreted into breast milk in small amounts. Monitor infant for drowsiness, irritability, and extrapyramidal symptoms. Manufacturer recommends caution. |
| Lactation Rating |
■ FDA Black Box Warning
Increased risk of death in elderly patients with dementia-related psychosis, similar to other antipsychotics.
| Serious Effects |
Hypersensitivity to prochlorperazine or any phenothiazineComatose statesSevere CNS depressionPediatric surgery (in children <2 years or <9 kg)
| Precautions | Tardive dyskinesia, Neuroleptic malignant syndrome, Extrapyramidal symptoms, Falls and fractures in elderly, Bone marrow suppression, QT prolongation, Hepatic impairment |
| Food/Dietary | No significant food interactions. Avoid excessive alcohol intake. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies; potential risk based on animal data (cleft palate, skeletal anomalies). Second/third trimesters: Risk of extrapyramidal symptoms and neonatal withdrawal with chronic use. Avoid use near term due to risk of maternal hypotension and neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal blood pressure (risk of hypotension), liver function tests (potential hepatotoxicity), and CBC (risk of leukopenia/agranulocytosis). Fetal monitoring: assess for neonatal extrapyramidal symptoms, respiratory depression, and withdrawal after delivery. In third trimester, consider fetal heart rate monitoring if used near term. |
| Fertility Effects | Prochlorperazine may increase prolactin levels, which can suppress gonadotropin-releasing hormone (GnRH) and lead to menstrual irregularities, anovulation, and reduced fertility. Effects are reversible upon discontinuation. In males, galactorrhea and gynecomastia may occur but impact on spermatogenesis is unclear. |
| COMPAZINE (prochlorperazine) is a phenothiazine antipsychotic with strong antiemetic properties. Monitor for extrapyramidal symptoms (EPS), especially in young and elderly patients. Avoid in patients with bone marrow depression or severe CNS depression. QT prolongation risk; check ECG in at-risk patients. Use with caution in hepatic impairment. |
| Patient Advice | Take exactly as prescribed. Do not stop suddenly without consulting your doctor. · May cause drowsiness or dizziness; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol and other CNS depressants. · Report any uncontrolled muscle movements, especially of the face or tongue. · Rise slowly from sitting or lying to prevent dizziness. |