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 |
| Molecular Weight | 284.42 |
| Action Class | Antihistamine (first-generation) / Antiemetic / Antitussive |
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 | Avoid due to potential teratogenic effects in animal studies; limited human data. |
| 2nd trimester | Use with caution only if clearly needed; no well-documented risk. |
| 3rd trimester | Avoid near term due to risk of respiratory depression and potential adverse effects on newborn (e.g., irritability, abnormal movements). |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Placental transfer | Promethazine crosses the placenta; DM (dextromethorphan) also crosses, but extent is limited. Neonatal respiratory depression and withdrawal symptoms reported with promethazine use near term. |
| Breastfeeding |
■ 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 | Respiratory depression (especially in children and with overdose), Severe CNS depression (drowsiness, confusion, coma), Extrapyramidal symptoms (dystonia, akathisia, tardive dyskinesia), Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic instability), Seizures, Cardiotoxicity (QT prolongation, arrhythmias), Severe hypotension, Agranulocytosis, Cholestatic jaundice, Paradoxical excitation (especially in children) |
Hypersensitivity to promethazine or dextromethorphanNewborns or premature infantsConcurrent use of MAO inhibitorsSevere respiratory depressionAcute asthma attackComatose statesEnzyme deficiency (e.g., CYP2D6 poor metabolizers with DM)
| 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…
| Small amounts excreted in breast milk; possible infant sedation or irritability. Avoid use during breastfeeding, especially in neonates or preterm infants due to immature drug metabolism. Monitor for drowsiness or poor feeding. |
| Lactation Rating | L3 (Moderately Safe) - limited data suggest risk but potential benefits may outweigh in some situations. |
| 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. |
| 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. |
| Food/Dietary | Avoid grapefruit juice as it may increase dextromethorphan levels and risk of side effects. Alcohol should be avoided due to additive sedation and respiratory depression. No other significant food interactions. |
| Clinical Pearls | Promethazine has anticholinergic effects; use cautiously in elderly, asthma, glaucoma, and prostatic hypertrophy. Dextromethorphan can cause serotonin syndrome with SSRIs, MAOIs. Avoid in children <2 years due to respiratory depression risk. Monitor for CNS depression, especially with alcohol or other sedatives. |
| Patient Advice | Do not use in children under 2 years old due to risk of serious breathing problems. · Avoid alcohol and other sedatives (e.g., benzodiazepines, opioids) as they increase drowsiness and respiratory depression. · Do not drive or operate heavy machinery until you know how this medication affects you. · Take with food if stomach upset occurs. Avoid grapefruit juice (may increase dextromethorphan levels). · Stop use and seek medical attention if you experience slow or shallow breathing, severe dizziness, or signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate). · Do not take with other cough/cold medications without consulting a healthcare provider. |