PROMETHACON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETHACON (PROMETHACON).
Promethazine is a phenothiazine derivative with antihistaminic (H1 receptor antagonist), antiemetic, sedative, and anticholinergic properties. It inhibits central and peripheral H1 receptors, blocks dopamine D2 receptors in the chemoreceptor trigger zone, and has weak alpha-adrenergic blockade.
| Metabolism | Primarily hepatic metabolism via glucuronidation and oxidation (CYP2D6 minor pathway). Major metabolites include promethazine sulfoxide and N-demethylpromethazine. |
| Excretion | Renal (80%) as inactive metabolites, 20% fecal via bile |
| Half-life | Terminal elimination half-life: 4-6 hours in healthy adults; prolonged to 10-14 hours in hepatic impairment |
| Protein binding | 93% bound, primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 9-12 L/kg; large Vd indicates extensive tissue distribution and high lipid solubility |
| Bioavailability | Oral: 25-30% due to extensive first-pass metabolism; Rectal: 70-80%; Intramuscular: 100% |
| Onset of Action | Oral: 20-30 minutes; Intramuscular: 10-20 minutes; Intravenous: 3-5 minutes; Rectal: 30-45 minutes |
| Duration of Action | Antiemetic and sedative effects last 4-6 hours; antihistamine effects up to 12 hours |
| Molecular Weight | 284.42 |
25-50 mg intramuscularly or intravenously every 4-6 hours as needed. Maximum intravenous rate: 25 mg/minute. Maximum daily dose: 150 mg.
| Dosage form | SUPPOSITORY |
| Renal impairment | No specific dose adjustment required for renal impairment. Use caution in severe renal impairment (eGFR <30 mL/min) due to accumulation of metabolites. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% or reduce frequency to every 6-8 hours. Child-Pugh Class C: Avoid use or reduce dose to 25% of normal and monitor closely. |
| Pediatric use | Children ≥2 years: 0.5-1 mg/kg intramuscularly or intravenously every 4-6 hours as needed. Maximum single dose: 25 mg for children <12 years, 50 mg for children 12-18 years. Not recommended for children <2 years. |
| Geriatric use | Initiate with 12.5-25 mg intramuscularly or intravenously every 6-8 hours due to increased sensitivity and prolonged half-life. Titrate cautiously and monitor for sedation, hypotension, and anticholinergic effects. Maximum dose: 100 mg/day. |
| 1st trimester | Avoid. Potential teratogenic effects; case reports of limb reduction defects. |
| 2nd trimester | Avoid. No clear evidence of safety; use only if clearly needed. |
| 3rd trimester | Avoid near term. Risk of respiratory depression and extrapyramidal symptoms in neonate. |
Clinical note
Comprehensive clinical and safety monograph for PROMETHACON (PROMETHACON).
| Placental transfer | Crosses placenta; detected in fetal tissues and amniotic fluid. |
| Breastfeeding | Excreted into breast milk in small amounts; may cause drowsiness or irritability in infant. Weigh benefits against risks. |
| Lactation Rating |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years due to the risk of fatal respiratory depression. Use in children aged 2 years and older requires extreme caution, especially when combined with other respiratory depressants.
| Serious Effects |
Hypersensitivity to promethazine or any phenothiazineComatose statesCNS depression from other agentsChildren <2 years (risk of respiratory depression)
| Precautions | Respiratory depression, especially in children and elderly, avoid use with other CNS depressants, Severe tissue injury (including gangrene) from intra-arterial injection or extravasation, Bone marrow suppression (agranulocytosis, leukopenia, thrombocytopenia), Neuroleptic malignant syndrome (rare), Seizure threshold lowering, Anticholinergic effects (urinary retention, glaucoma exacerbation), Tardive dyskinesia with prolonged use |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice as it may increase promethazine levels. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects and oral clefts. Second and third trimesters: Risk of fetal growth restriction and preterm birth. Late third trimester: Neonatal withdrawal syndrome (tremors, irritability, poor feeding) if used chronically. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, sedation level, respiratory rate. Fetal: Heart rate monitoring nonstress test starting at 32 weeks. Ultrasound for fetal growth every 4 weeks from 28 weeks. |
| Fertility Effects | Promethazine may suppress ovulation via prolactin elevation and anticholinergic effects. Reversible upon discontinuation. No long-term impact on fertility in females. |
| Clinical Pearls | Promethacon (promethazine) is a phenothiazine derivative with strong antiemetic, antihistaminic, and sedative properties. Avoid intra-arterial injection due to risk of gangrene. Use with caution in children <2 years due to risk of respiratory depression. Monitor for extrapyramidal symptoms, especially in elderly. Can cause QT prolongation; avoid with other QT-prolonging drugs. |
| Patient Advice | May cause drowsiness; avoid driving or operating machinery until you know how you react. · Avoid alcohol and other CNS depressants. · Report any involuntary muscle movements, especially in the face or tongue. · Do not use in children under 2 years old. · If you are pregnant or breastfeeding, consult your doctor before taking this medication. |