PROMETHAZINE W/ DEXTROMETHORPHAN
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 and antiemetic; dextromethorphan is a non-opioid antitussive that acts as an NMDA receptor antagonist and sigma-1 receptor agonist.
| Metabolism | Promethazine is metabolized in the liver via CYP2D6; dextromethorphan is metabolized via CYP2D6 to active metabolite dextrorphan. |
| Excretion | Renal: promethazine ~6% unchanged, dextromethorphan ~0.5% unchanged; metabolites primarily renal. Biliary/fecal: minor routes for both. |
| Half-life | Promethazine: 9-16 h; dextromethorphan: 3-5 h (extensive metabolizers), 30-50 h (poor metabolizers). Clinical context: dosing interval typically 4-6 h for dextromethorphan; promethazine accumulates with repeated dosing. |
| Protein binding | Promethazine: 88-93% bound to albumin; dextromethorphan: 60-70% bound to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Promethazine: Vd 12-18 L/kg (large, extensive tissue distribution); dextromethorphan: Vd 5-7 L/kg (moderate). |
| Bioavailability | Promethazine: oral ~25% (extensive first-pass metabolism), rectal ~25%; dextromethorphan: oral 50-70% (extensive first-pass metabolism). |
| Onset of Action | Oral: promethazine 20-30 min, dextromethorphan 30-60 min. Rectal: promethazine similar. |
| Duration of Action | Promethazine: 6-12 h; dextromethorphan: 5-6 h. Clinical notes: promethazine may cause prolonged sedation; dextromethorphan effects last 5-6 h. |
5 mL (containing promethazine 6.25 mg and dextromethorphan 15 mg) orally every 4-6 hours as needed, not to exceed 30 mL (promethazine 37.5 mg, dextromethorphan 90 mg) per 24 hours.
| Dosage form | SYRUP |
| Renal impairment | GFR 30-50 mL/min: No adjustment needed. GFR 10-29 mL/min: Use with caution; reduce dose by 50% or extend interval. GFR <10 mL/min: Avoid use due to risk of accumulation of dextromethorphan metabolites. |
| Liver impairment | Child-Pugh Class A (mild): No adjustment. Child-Pugh Class B (moderate): Reduce dose by 50% or extend interval. Child-Pugh Class C (severe): Avoid use due to reduced clearance of both components. |
| Pediatric use | Children 12 years and older: 5 mL (promethazine 6.25 mg/dextromethorphan 15 mg) orally every 4-6 hours, not to exceed 30 mL in 24 hours. Children 6 to under 12 years: 2.5 mL (promethazine 3.125 mg/dextromethorphan 7.5 mg) orally every 4-6 hours, not to exceed 15 mL in 24 hours. Children under 6 years: Not recommended due to risk of respiratory depression. |
| Geriatric use | Use with caution; initiate at the lower end of the dosing range (e.g., 2.5-5 mL every 6 hours) due to increased sensitivity and risk of anticholinergic effects, sedation, and falls. Avoid in patients with significant cognitive impairment or increased fall risk. |
| 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 into breast milk in small amounts (M/P ratio ~0.4-0.8); may cause drowsiness or irritability in infants. Dextromethorphan likely excreted in milk but data limited. Use only if benefit outweighs risk; monitor infant for sedation and feeding difficulties. American Academy of Pediatrics recommends avoiding promethazine during breastfeeding due to potential for respiratory depression. |
| Teratogenic Risk |
■ FDA Black Box Warning
Do not use in children younger than 6 years due to risk of respiratory depression and death; avoid use in children <2 years.
| Common Effects | nausea/vomiting |
| Serious Effects |
Hypersensitivity to any component, children <2 years, neonates/premature infants, breastfeeding (promethazine may impair lactation), concurrent MAOI use (or within 14 days), severe CNS depression, comatose states.
| Precautions | Respiratory depression (especially in children and elderly), CNS depression, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome (rare), photosensitivity, impaired cognitive/motor function. |
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| FDA Pregnancy Category C. First trimester: Limited data; animal studies with promethazine show skeletal abnormalities at high doses; dextromethorphan not clearly teratogenic but weak association with neural tube defects in some studies. Second and third trimesters: No known specific malformations; avoid near term due to risk of neonatal respiratory depression and extrapyramidal effects from promethazine. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status; assess for excessive sedation or extrapyramidal symptoms. Fetal monitoring: heart rate and movement patterns; ultrasound for growth if used chronically. Near term: monitor newborn for respiratory depression, hypotonia, and poor feeding. |
| Fertility Effects | Promethazine may elevate prolactin levels, potentially causing galactorrhea, menstrual irregularities, and reversible ovulation suppression. Dextromethorphan has no known direct effect on fertility. Limited data on combination; consider potential endocrine disruption. |