PHENERGAN VC W/ CODEINE
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur especially in CYP2D6 ultra-rapid metabolizers.
Phenergan VC w/ Codeine combines codeine (opioid agonist, mu-receptor), promethazine (histamine H1 antagonist, anticholinergic, sedative), and phenylephrine (alpha-1 adrenergic agonist). Codeine is metabolized to morphine for analgesia and antitussive effects; promethazine suppresses cough via central nervous system depression; phenylephrine causes vasoconstriction to relieve congestion.
| Metabolism | Codeine: primarily metabolized by CYP2D6 to morphine (active) and by CYP3A4 to norcodeine; further glucuronidation. Promethazine: metabolized via CYP2D6 and CYP2B6. Phenylephrine: metabolized by monoamine oxidase (MAO) and sulfation. |
| Excretion | Codeine: renal elimination of metabolites (codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide, morphine-6-glucuronide); ~90% excreted in urine, <10% in feces. Promethazine: renal and biliary elimination as metabolites and unchanged drug; ~70-80% in urine, <20% in feces. |
| Half-life | Codeine: terminal half-life ~3 hours (range 2.5-4.5 h) in adults; extended in renal impairment. Promethazine: terminal half-life ~10-14 hours (range 7-20 h) in adults; prolonged in elderly and hepatic impairment. |
| Protein binding | Codeine: ~7-25% bound primarily to albumin. Promethazine: ~93% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Codeine: ~3-6 L/kg (high tissue distribution). Promethazine: ~12-18 L/kg (extensive tissue binding, large Vd). |
| Bioavailability | Codeine: oral bioavailability ~50-70% (first-pass metabolism); IM ~100%. Promethazine: oral bioavailability ~25-40% (extensive first-pass); IM/IV ~100%. |
| Onset of Action | Oral: codeine onset 30-60 minutes; promethazine onset 20-30 minutes; IM/IV promethazine onset within 5-10 minutes; codeine IM onset 10-30 minutes. |
| Duration of Action | Codeine: analgesic duration 4-6 hours; antitussive duration 4-6 hours. Promethazine: antihistamine/sedative duration 6-12 hours; antiemetic duration up to 12 hours. Combination effect persists 4-6 hours. |
1 to 2 teaspoonfuls (5-10 mL) orally every 4 to 6 hours as needed. Maximum 4 doses in 24 hours.
| Dosage form | SYRUP |
| Renal impairment | Not recommended in severe renal impairment (CrCl <30 mL/min). Use with caution in moderate impairment (CrCl 30-60 mL/min) with extended dosing intervals. No specific dose adjustment provided. |
| Liver impairment | No specific Child-Pugh based recommendations. Use with caution in severe hepatic impairment; consider reduced dosing or extended intervals due to risk of accumulation. |
| Pediatric use | Children 6-12 years: 1 teaspoonful (5 mL) orally every 4-6 hours. Maximum 4 doses in 24 hours. Contraindicated in children <6 years due to risk of respiratory depression. |
| Geriatric use | Initiate with lowest effective dose (e.g., 1 teaspoonful) and monitor for CNS depression, falls, and anticholinergic effects. Consider alternative therapies due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur especially in CYP2D6 ultra-rapid metabolizers.
| FDA category | Positive |
| Breastfeeding | Codeine: excreted into breast milk; M/P ratio ~2.5. Risk of infant CNS depression, especially in ultra-rapid metabolizers of CYP2D6. Promethazine: excreted in small amounts; may cause drowsiness or irritability in the infant. Avoid in breastfeeding due to combination and potential for infant sedation and respiratory depression. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: RESPIRATORY DEPRESSION, DEATH, AND ADDICTION. Codeine can cause respiratory depression, especially in children. Contraindicated in children <12 years; not recommended for children 12-18 with obesity, neuromuscular disease, or compromised respiratory function. Risk of opioid addiction, abuse, and misuse. Concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death.
| Common Effects | cough |
| Serious Effects |
["Hypersensitivity to codeine, promethazine, phenylephrine, or any component","Children <12 years of age","Concomitant use with MAO inhibitors or within 14 days","Severe hypertension or coronary artery disease (phenylephrine)","Acute asthma or respiratory depression","Obstructive sleep apnea or neuromuscular disease (in adolescents)","Breastfeeding (risk of infant respiratory depression)","Concomitant use with alcohol or other CNS depressants"]
| Precautions | ["Risk of respiratory depression, especially with CYP2D6 ultra-rapid metabolizers","Avoid in children due to risk of respiratory depression","Serotonin syndrome risk with serotonergic drugs","Anticholinergic effects (urinary retention, blurred vision, constipation) from promethazine","Cardiovascular effects from phenylephrine (hypertension, arrhythmias)","May impair mental/physical abilities; avoid driving","Risk of severe hypotension with phenothiazines","Use caution in hepatic/renal impairment, asthma, COPD, seizures, or increased intracranial pressure"] |
Loading safety data…
| First trimester: Limited data; codeine has been associated with increased risk of congenital malformations (particularly cardiac defects) in some studies. Phenergan (promethazine) has conflicting data, with some studies suggesting small increased risk of malformations. Second and third trimesters: Codeine use near term may cause neonatal respiratory depression and withdrawal. Promethazine near term may cause CNS depression, extrapyramidal signs, or jaundice. Overall, risks are low but not negligible. |
| Fetal Monitoring | Monitor maternal respiratory status, sedation level, and bowel function. Fetal monitoring for heart rate variability and signs of distress. Neonatal monitoring for respiratory depression, withdrawal symptoms (irritability, poor feeding), and jaundice postpartum. |
| Fertility Effects | No direct studies on fertility effects in humans. Codeine may suppress gonadotropin release via opioid receptors, potentially impacting menstrual cycle and ovulation. Promethazine may cause hyperprolactinemia, but effects on fertility are unknown. Clinical significance is likely low with short-term use. |