PHERAZINE DM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHERAZINE DM (PHERAZINE DM).
Phererazine DM is a combination of promethazine (a phenothiazine derivative with antihistaminic, sedative, antiemetic, and anticholinergic properties) and dextromethorphan (a non-opioid antitussive that acts on the sigma-1 receptor and NMDA receptor antagonist). Promethazine blocks H1 receptors and reduces histamine-mediated symptoms, while dextromethorphan suppresses cough by central action on the cough center.
| Metabolism | Promethazine: extensively metabolized in the liver via oxidation (CYP2D6) and glucuronidation; Dextromethorphan: metabolized by CYP2D6 to dextrorphan (active) and other metabolites. |
| Excretion | Primarily renal: 60-70% as unchanged drug and glucuronide conjugate; 15-20% fecal via biliary excretion. |
| Half-life | Terminal elimination half-life: 3-4 hours in children; 5-6 hours in adults; up to 8 hours in elderly. Clinical context: Dosing interval adjustment needed in renal impairment. |
| Protein binding | 65-75% mainly to albumin; also binds to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 3-5 L/kg. Indicates extensive tissue distribution, including CNS penetration. |
| Bioavailability | Oral: 40-50% (due to first-pass metabolism); Rectal: 50-60%; Intramuscular: 70-90%. |
| Onset of Action | Oral: 15-30 minutes; Rectal: 20-40 minutes; Intramuscular: 10-15 minutes. |
| Duration of Action | Oral/rectal: 4-6 hours; Intramuscular: 3-4 hours. Clinical note: Duration may be prolonged in hepatic impairment. |
Adults: 1 tablet (promethazine 25 mg / dextromethorphan 30 mg) orally every 6-8 hours as needed; maximum 4 tablets per day.
| Dosage form | SYRUP |
| Renal impairment | CrCl 10-50 mL/min: administer 75% of normal dose every 6-8 hours. CrCl <10 mL/min: administer 50% of normal dose every 8-12 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: contraindicated. |
| Pediatric use | Children 2-6 years: 1.25 mg/kg/day promethazine plus 1 mg/kg/day dextromethorphan divided every 6-8 hours, maximum 75 mg/day promethazine. Children 6-12 years: 6.25-12.5 mg promethazine plus 15-30 mg dextromethorphan every 6-8 hours. Not recommended under 2 years. |
| Geriatric use | Initiate at half the adult dose; maximum 2 tablets per day. Use with caution due to anticholinergic effects and increased fall risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHERAZINE DM (PHERAZINE DM).
| Breastfeeding | Dextromethorphan: Small amounts excreted, M/P ratio unknown; considered compatible. Promethazine: Excreted in low levels, M/P ratio ~0.7-1.3; may cause drowsiness in infant. Phentolamine: Not applicable (phenylephrine not in lactation). Generally use with caution; monitor infant for sedation. |
| Teratogenic Risk | PHE razi ne DM (dextromethorphan/promethazine/phenylephrine): First trimester: Dextromethorphan limited data, not associated with major malformations; promethazine not associated with major malformations; phenylephrine limited data, possible association with minor malformations. Second/third trimester: Promethazine may cause respiratory depression in neonate if used near term; phenylephrine may reduce uterine blood flow and cause fetal hypoxia. Avoid in first trimester; restrict in later trimesters. |
■ FDA Black Box Warning
Warning: Respiratory depression in children under 2 years of age; use in children <2 years contraindicated. Risk of respiratory depression and death in pediatric patients. Do not use in combination with CNS depressants in children. Contraindicated in children <2 years.
| Serious Effects |
Children <2 years of age; known hypersensitivity to promethazine, dextromethorphan, or any component; use with MAO inhibitors or within 14 days; concurrent use of high doses of CNS depressants; asthma attack; convulsive disorders; pregnancy (risk of respiratory depression in neonates).
| Precautions | Respiratory depression in children; CNS depression; anticholinergic effects (e.g., urinary retention, blurred vision); extrapyramidal reactions; neuroleptic malignant syndrome; sedation; avoid alcohol and other CNS depressants; use with caution in asthma, COPD, glaucoma, prostatic hypertrophy, pyloroduodenal obstruction. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and uterine activity. Fetal monitoring for heart rate changes, especially with phenylephrine. In third trimester, assess neonatal respiratory status if promethazine used near term. |
| Fertility Effects | No known adverse effects on fertility from dextromethorphan or promethazine. Phenylephrine may theoretically affect uterine blood flow but no fertility impairment documented. |