PROMETHAZINE DM
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, antiemetic via blockade of dopamine D2 receptors in the chemoreceptor trigger zone, and sedative via central anticholinergic effects. Dextromethorphan is an NMDA receptor antagonist and sigma-1 receptor agonist, suppressing cough by central action on the cough center.
| Metabolism | Promethazine: Primarily hepatic via CYP2D6 and conjugation. Dextromethorphan: Hepatic via CYP2D6 to active metabolite dextrorphan; CYP3A4 and CYP2C9 also contribute. |
| Excretion | Renal (70-80% as metabolites, <1% unchanged); biliary/fecal (20-30%) |
| Half-life | 16-19 hours (terminal); note: effect may last longer due to active metabolites and tissue binding |
| Protein binding | 93% bound primarily to albumin and alpha1-acid glycoprotein |
| Volume of Distribution | 9-15 L/kg; extensive tissue distribution with high CNS penetration |
| Bioavailability | Oral: ~25% due to first-pass metabolism; IM: ~80-90%; IV: 100%; Rectal: ~70-80% |
| Onset of Action | Oral: 20-30 minutes; IM: 10-20 minutes; IV: 3-5 minutes; Rectal: 30-60 minutes |
| Duration of Action | 4-6 hours (antiemetic); 6-12 hours (sedation); up to 24 hours for antihistamine effects |
2 teaspoonfuls (10 mL) orally every 4-6 hours, not to exceed 8 teaspoonfuls (40 mL) per 24 hours.
| Dosage form | SYRUP |
| Renal impairment | No specific guidelines. Use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of promethazine. |
| Liver impairment | Avoid use in severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B), reduce dose by 50% and monitor for CNS depression. |
| Pediatric use | Children 6-12 years: 1 teaspoonful (5 mL) orally every 4-6 hours, not to exceed 4 teaspoonfuls (20 mL) per 24 hours. Children 2-5 years: 0.5 teaspoonful (2.5 mL) orally every 4-6 hours, not to exceed 2 teaspoonfuls (10 mL) per 24 hours. Not recommended for children <2 years due to risk of respiratory depression. |
| Geriatric use | Initiate at lowest effective dose (e.g., 2.5-5 mL) and monitor for sedation, confusion, and anticholinergic effects. Avoid in patients with dementia or Parkinson's disease. Maximum dose: 4 teaspoonfuls (20 mL) per 24 hours. |
| 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 small amounts; M/P ratio not reported. Dextromethorphan excretion not well-studied. Use caution and monitor infant for sedation or irritability. |
| Teratogenic Risk | First trimester: Animal studies insufficient; human data limited. Risk cannot be excluded. Second and third trimesters: No known specific fetal risks, but dextromethorphan is generally avoided near term due to potential neonatal respiratory depression. |
■ FDA Black Box Warning
Promethazine: Respiratory depression, including fatalities, in children <2 years due to antihistamine effects; contraindicated in this age group. Dextromethorphan: No boxed warning.
| Common Effects | nausea/vomiting |
| Serious Effects |
Absolute: Children <2 years, hypersensitivity to promethazine or dextromethorphan, coma, CNS depression, concurrent MAOI therapy (hypertensive crisis). Relative: Asthma, COPD, sleep apnea, prostatic hypertrophy, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bladder neck obstruction, elderly with confusion/dementia, lactation.
| Precautions | CNS depression (additive with other depressants), respiratory depression (especially in children, elderly, or with respiratory impairment), anticholinergic effects (dry mouth, urinary retention, blurred vision), extrapyramidal reactions, neuroleptic malignant syndrome (rare), photosensitivity, avoid use in dehydration/electrolyte imbalances, may mask signs of intestinal obstruction. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status. Assess fetal heart rate if maternal sedation or hypotension occurs. Observe newborn for signs of respiratory depression or withdrawal if used chronically near delivery. |
| Fertility Effects | Animal studies suggest no significant effect on fertility at therapeutic doses. Human data limited. |