CODAMINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CODAMINE (CODAMINE).
Codeine is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. It is a prodrug converted to morphine via CYP2D6.
| Metabolism | Hepatic via CYP2D6 to morphine (active) and CYP3A4 to norcodeine; also glucuronidation. |
| Excretion | Renal: 60% unchanged; Biliary/Fecal: 30% as metabolites; 10% other |
| Half-life | Terminal elimination half-life: 4–6 hours in adults; prolonged to 8–12 hours in renal impairment (CrCl <30 mL/min) |
| Protein binding | ~92% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 1.2 L/kg (range 0.8–1.6 L/kg), indicating extensive tissue distribution |
| Bioavailability | Oral: 65–75% (first-pass effect); Rectal: 50–60%; Intramuscular: 90% |
| Onset of Action | Oral: 30–60 minutes; Intravenous: 2–5 minutes; Intramuscular: 10–15 minutes |
| Duration of Action | Oral: 4–6 hours; Intravenous: 3–5 hours; Intramuscular: 4–6 hours; Duration may be extended in hepatic impairment |
| Molecular Weight | 299.4 |
Adults: 1-2 tablets (codeine 30 mg + acetaminophen 500 mg per tablet) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
| Dosage form | SYRUP |
| Renal impairment | GFR 30-50 mL/min: Use with caution, reduce dose by 25-50% or extend interval to every 6-8 hours. GFR <30 mL/min: Avoid use due to risk of codeine accumulation and toxicity. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% and monitor for sedation. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Weight-based codeine dosing: 0.5-1 mg/kg every 4-6 hours as needed; maximum 60 mg per dose. Acetaminophen component: 10-15 mg/kg every 4-6 hours; maximum 75 mg/kg per day. Not recommended in children under 12 years due to risk of respiratory depression. |
| Geriatric use | Start at lower end of dosing range (e.g., 1 tablet every 6 hours) due to increased sensitivity and risk of respiratory depression, constipation, and sedation. Monitor renal and hepatic function. |
| 1st trimester | Avoid. Animal studies show teratogenic effects; no adequate human studies. |
| 2nd trimester | Use only if potential benefit outweighs risk. May cause fetal respiratory depression if used near term. |
| 3rd trimester | Use only if potential benefit outweighs risk. May cause neonatal withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for CODAMINE (CODAMINE).
| Placental transfer | Crosses placenta rapidly; cord blood levels approach maternal levels. |
| Breastfeeding | Excreted in breast milk in low concentrations; monitor infant for sedation and respiratory depression. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | CODAMINE is classified as FDA Pregnancy Category D. First trimester: Associated with increased risk of cardiovascular and neural tube defects. Second trimester: Potential for fetal growth restriction and oligohydramnios. Third trimester: Risk of neonatal withdrawal, respiratory depression, and persistent pulmonary hypertension. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status. Perform fetal ultrasound for growth and amniotic fluid index. Nonstress test or biophysical profile in third trimester. Monitor neonatal for withdrawal symptoms post-delivery. |
| Fertility Effects | CODAMINE may impair fertility in both sexes by reducing libido and causing menstrual irregularities or erectile dysfunction. Animal studies show reduced conception rates and spermatogenesis impairment. Reversible upon discontinuation. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; AND RISK OF MEDICATION ERRORS.
| Serious Effects |
Known hypersensitivitySevere respiratory depressionAcute or severe bronchial asthmaParalytic ileus
| Precautions | Risk of respiratory depression, especially in children; ultra-rapid metabolizers (CYP2D6 duplications) may experience life-threatening toxicity; avoid use post-tonsillectomy/adenoidectomy in children; risk of opioid-induced hyperalgesia; adrenal insufficiency; severe hypotension; seizures; serotonin syndrome with serotonergic drugs; GI obstruction; impaired mental/physical abilities. |
| Food/Dietary | Avoid grapefruit juice as it may alter metabolism of codeine. High-fiber meals may help with constipation; avoid excessive alcohol. St. John's Wort may reduce codeine efficacy. |
| Clinical Pearls | Codamine is a combination of codeine and an antihistamine (e.g., promethazine or chlorpheniramine). Caution: risk of respiratory depression, especially in elderly or with lung disease. Monitor for constipation. Avoid in children under 12 due to risk of respiratory depression. Use lowest effective dose for shortest duration. Antihistamine component may cause anticholinergic effects (dry mouth, urinary retention, blurred vision). |
| Patient Advice | Do not exceed recommended dose; risk of serious side effects like slowed breathing. · Avoid alcohol and other sedatives (benzodiazepines, sleeping pills) as they increase drowsiness and breathing problems. · Do not drive or operate machinery until you know how this medication affects you. · Take with food to reduce stomach upset; drink plenty of fluids to prevent constipation. · Stop use and seek medical help if you experience difficulty breathing, severe dizziness, or allergic reaction. · Store safely out of reach of children; dispose of unused medication properly to prevent accidental overdose. · Do not use if you have a history of drug abuse or addiction. · Inform your doctor if you are pregnant, breastfeeding, or have lung/liver/kidney/thyroid problems. |
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