PROMAZINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMAZINE HYDROCHLORIDE (PROMAZINE HYDROCHLORIDE).
Promazine hydrochloride is a phenothiazine antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic system, as well as histamine H1, alpha-1 adrenergic, and muscarinic cholinergic receptors. It also has moderate serotonin and weak serotonin-dopamine antagonist effects.
| Metabolism | Extensively metabolized in the liver primarily via CYP2D6 and flavin-containing monooxygenase (FMO) pathways to multiple metabolites, including promazine sulfoxide and N-demethylated derivatives. |
| Excretion | Primarily renal (approx. 70-80% as metabolites, <1% unchanged); minor biliary/fecal (approx. 15-20%) |
| Half-life | Terminal elimination half-life: 12-18 hours; in elderly or hepatic impairment may extend to 30 hours |
| Protein binding | 80-90% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 8-10 L/kg (extensive tissue distribution, crosses blood-brain barrier) |
| Bioavailability | Oral: approximately 20-30% due to extensive first-pass metabolism; IM: near 100% |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes; IV: 5-10 minutes |
| Duration of Action | Oral/IM: 4-6 hours; IV: 3-4 hours; prolonged with depot formulations (not applicable to promazine hydrochloride) |
25-50 mg intramuscularly every 4-6 hours as needed. Maximum 150 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required; use with caution in severe renal impairment (eGFR <30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). In mild to moderate impairment (Child-Pugh A or B), start at half the usual dose and titrate cautiously. |
| Pediatric use | For children >2 years and <12 years: 0.5-1 mg/kg intramuscularly every 4-6 hours, not to exceed 40 mg/day. Use is not recommended for children under 2 years. |
| Geriatric use | Initiate at 10-25 mg intramuscularly every 4-6 hours, with careful monitoring for hypotension, sedation, and extrapyramidal symptoms. Lower total daily doses recommended. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMAZINE HYDROCHLORIDE (PROMAZINE HYDROCHLORIDE).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Potential for infant sedation and extrapyramidal effects. Use caution; monitor infant for drowsiness, irritability, and feeding difficulties. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show fetal harm at high doses. Second/third trimester: Risk of neonatal extrapyramidal symptoms, sedation, and withdrawal if used near term. Avoid unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis; not approved for this use.
| Serious Effects |
Comatose states, central nervous system depression, bone marrow suppression, known hypersensitivity to promazine or other phenothiazines, severe hypotension, and concurrent use of high doses of central nervous system depressants.
| Precautions | May cause tardive dyskinesia, neuroleptic malignant syndrome (NMS), QT prolongation, orthostatic hypotension, leukopenia, agranulocytosis, seizures, anticholinergic effects, and photosensitivity. Use with caution in patients with cardiovascular disease, hepatic or renal impairment, prostatic hypertrophy, glaucoma, and seizure disorders. |
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| Monitor maternal blood pressure, heart rate, and ECG for arrhythmias. Observe neonate for jaundice, extrapyramidal symptoms, and respiratory depression if used near delivery. Periodic liver function tests due to rare cholestatic jaundice. |
| Fertility Effects | May cause hyperprolactinemia leading to menstrual irregularities, anovulation, and reduced fertility in females. In males, possible sexual dysfunction; effect is reversible upon discontinuation. |