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) |
| Molecular Weight | 284.36 |
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 | Limited human data; animal studies not available. Use only if potential benefit justifies potential risk to fetus. Avoid during first trimester if possible due to potential teratogenicity risk. |
| 2nd trimester | Use only if clearly needed; no well-controlled studies in pregnant women. |
| 3rd trimester | May cause extrapyramidal symptoms or withdrawal in neonates after delivery; use near term may affect neonatal adaptation. |
Clinical note
Comprehensive clinical and safety monograph for PROMAZINE HYDROCHLORIDE (PROMAZINE HYDROCHLORIDE).
| Placental transfer | Crosses the placenta; detectable in fetal plasma; degree of transfer not fully quantified. |
| Breastfeeding | Promazine is excreted in breast milk in low concentrations. Monitor infant for drowsiness, irritability, and poor feeding. Consider benefits of breastfeeding vs potential risks. Not recommended for nursing mothers due to lack of safety data. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis; not approved for this use.
| Serious Effects |
Coma or severe CNS depressionPheochromocytomaHypersensitivity to promazine or phenothiazinesBone marrow suppression
| 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. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Grapefruit juice may inhibit CYP450 3A4 metabolism, potentially increasing promazine levels. No other specific food restrictions. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - limited data, potential effects |
| 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 | 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. |
| Clinical Pearls | Promazine hydrochloride is a first-generation antipsychotic primarily used for agitation and psychotic disorders. Monitor for extrapyramidal symptoms (EPS) and tardive dyskinesia, especially in elderly patients. Avoid in patients with QT prolongation or electrolyte disturbances; obtain baseline ECG and correct hypokalemia/hypomagnesemia. Use with caution in epilepsy due to lowered seizure threshold. Parenteral administration can cause hypotension; observe for 30 minutes post-injection. Not recommended for dementia-related psychosis due to increased mortality risk. |
| Patient Advice | Avoid alcohol and CNS depressants (e.g., opioids, benzodiazepines) as they increase sedation and respiratory depression risk. · Rise slowly from sitting or lying position to prevent dizziness or fainting from low blood pressure. · Report involuntary muscle movements (e.g., lip smacking, tongue protrusion) or stiffness immediately. · May cause drowsiness; avoid driving or operating heavy machinery until effects are known. · Take exactly as prescribed; do not stop abruptly without consulting your doctor. · Limit sun exposure and use sunscreen as this drug increases sun sensitivity. |