NALMEFENE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NALMEFENE HYDROCHLORIDE (NALMEFENE HYDROCHLORIDE).
Nalmefene is an opioid receptor antagonist with high affinity for mu, kappa, and delta receptors, and partial agonist activity at kappa receptors.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7) and oxidation (CYP3A4/5); major metabolite is nalmefene 3-glucuronide. |
| Excretion | Primarily renal (approximately 50% unchanged drug); biliary/fecal excretion accounts for ~20% |
| Half-life | Terminal elimination half-life: ~10.8 hours (range 8–13 hours); clinically supports twice-daily dosing or use in alcohol use disorder |
| Protein binding | Approximately 45% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | Approximately 3.5 L/kg; indicates extensive extravascular distribution |
| Bioavailability | Oral: ~40% (extensive first-pass metabolism); subcutaneous: ~95%; intravenous: 100% |
| Onset of Action | Intravenous: ~5 minutes; subcutaneous: ~15 minutes; oral: ~30 minutes |
| Duration of Action | Intravenous: 2–4 hours (dose-dependent); subcutaneous: 2–4 hours; oral: up to 24 hours due to long terminal half-life |
18 mcg intranasally once, repeated after 2-3 minutes if needed; maximum 2 doses (36 mcg) per episode. Alternatively, 0.5 mg subcutaneously or intramuscularly once, repeated after 2-3 minutes if needed; maximum 1.5 mg per episode.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Avoid use in severe renal impairment (CrCl <30 mL/min) due to lack of safety data. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 9 mcg intranasally or 0.25 mg subcutaneously/intramuscularly. Child-Pugh C: Not recommended. |
| Pediatric use | Not approved for pediatric patients below 18 years of age. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; monitor for potential increased sensitivity or adverse effects. Use with caution due to higher prevalence of renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NALMEFENE HYDROCHLORIDE (NALMEFENE HYDROCHLORIDE).
| Breastfeeding | No data available on excretion into human milk. M/P ratio unknown. Caution advised due to potential for adverse effects in nursing infant. |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Should be used during pregnancy only if clearly needed. First trimester: No known teratogenic effects reported. Second and third trimesters: No data on adverse fetal outcomes. |
| Fetal Monitoring |
■ FDA Black Box Warning
Risk of sudden opioid withdrawal in opioid-dependent patients.
| Serious Effects |
["Hypersensitivity to nalmefene","Known or suspected opioid dependence","Acute opioid withdrawal syndrome"]
| Precautions | ["May precipitate withdrawal in opioid-dependent patients","Risk of opioid overdose resurgence due to shorter duration of action than some opioids","Hypersensitivity reactions","Use with caution in renal impairment"] |
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| Monitor for signs of opioid withdrawal in mother (e.g., hypertension, tachycardia, nausea, vomiting) and fetal distress if used in pregnancy. |
| Fertility Effects | No data on effects on human fertility. Animal studies suggest no impairment of fertility. |