PROMETHAZINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
Promethazine is a phenothiazine derivative that acts as a histamine H1 receptor antagonist, blocking the effects of histamine at H1 receptors. It also has anticholinergic, antiemetic, sedative, and antidopaminergic properties.
| Metabolism | Primarily hepatic metabolism via CYP2D6 to promethazine sulfoxide and other metabolites; also undergoes S-oxidation and N-demethylation. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for <1% of unchanged drug; biliary/fecal excretion of metabolites ~70-80%. |
| Half-life | Terminal elimination half-life is 10-19 hours in adults; prolonged in hepatic impairment (up to 30+ hours) and in elderly. |
| Protein binding | 93% bound primarily to albumin. |
| Volume of Distribution | 9-16 L/kg; indicates extensive tissue distribution and accumulation in tissues. |
| Bioavailability | Oral: ~25% due to first-pass metabolism; IM: ~70-80%; IV: 100%; rectal: ~25-30%. |
| Onset of Action | Oral: 20-30 minutes; IM: 15-20 minutes; IV: 3-5 minutes; rectal: 30-60 minutes. |
| Duration of Action | 5-6 hours for oral/IM/rectal; 4-6 hours for IV; clinical effects may persist longer due to active metabolites. |
25-50 mg intramuscular or intravenous injection every 4-6 hours as needed; also 12.5-25 mg orally every 4-6 hours.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (CrCl <10 mL/min) due to risk of accumulation. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use or reduce dose by 75%. |
| Pediatric use | 2-6 years: 5-6.25 mg orally every 4-6 hours; 6-12 years: 6.25-12.5 mg orally every 4-6 hours; >12 years: as adult; intramuscular: 0.25-0.5 mg/kg every 4-6 hours. |
| Geriatric use | Start at lowest effective dose (e.g., 12.5 mg orally or 12.5-25 mg IM/IV); increase cautiously due to increased risk of sedation, confusion, and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Breastfeeding | Promethazine is excreted in breast milk in low concentrations; M/P ratio not established. Due to risk of drowsiness and irritability in nursing infants avoid use, especially in neonates or preterm infants. AAP classifies as compatible but caution advised. |
| Teratogenic Risk | First trimester: Limited human data, no increased risk of major malformations from population-based studies. Second and third trimesters: Use associated with transient neonatal extrapyramidal signs, sedation, withdrawal symptoms if used near term. May inhibit neonatal platelet aggregation. |
■ FDA Black Box Warning
Promethazine is contraindicated in children less than 2 years of age due to risk of fatal respiratory depression. Use in children 2 years and older should be avoided with other respiratory depressants.
| Common Effects | nausea/vomiting |
| Serious Effects |
["Hypersensitivity to promethazine or other phenothiazines","Children less than 2 years of age","Comatose patients or those receiving large doses of other CNS depressants","Seizure disorders (may lower seizure threshold)","Prostatic hypertrophy, bladder neck obstruction","Angle-closure glaucoma","Symptomatic prostatic hypertrophy"]
| Precautions | ["Risk of respiratory depression, especially in children","CNS depression; avoid with alcohol or other sedatives","May cause bone marrow suppression, agranulocytosis","Anticholinergic effects (e.g., urinary retention, blurred vision)","Extrapyramidal reactions, tardive dyskinesia","Neuroleptic malignant syndrome (rare)","May elevate prolactin levels","Interference with pregnancy test"] |
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| Fetal Monitoring | Monitor maternal blood pressure for hypotension, fetal heart rate variability if used in labor, neonatal respiratory depression and extrapyramidal symptoms after delivery. |
| Fertility Effects | No specific studies; animal studies show some anti-fertility effects at high doses, but human relevance unknown. |