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 |
| Molecular Weight | 417.33 |
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 | Limited human data; animal studies show no teratogenicity at clinically relevant doses but risk cannot be excluded. Use only if potential benefit justifies risk. |
| 2nd trimester | No adequate human studies; animal studies show no fetal harm at therapeutic doses. Use with caution. |
| 3rd trimester | Use near term may precipitate opioid withdrawal in the fetus/neonate. Avoid unless clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for NALMEFENE HYDROCHLORIDE (NALMEFENE HYDROCHLORIDE).
| Placental transfer | Likely crosses placenta due to low molecular weight and lipophilicity; no quantitative data. |
| Breastfeeding | No human data on excretion in breast milk; low molecular weight suggests possible transfer. Use with caution, monitor infant for withdrawal symptoms. |
■ FDA Black Box Warning
Risk of sudden opioid withdrawal in opioid-dependent patients.
| Serious Effects |
Hypersensitivity to nalmefene or any componentConcurrent use of opioid analgesics or acute opioid intoxicationHistory of opioid dependence and current opioid use
| 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 |
| Food/Dietary | Alcohol: Nalmefene is used to reduce alcohol consumption, but concomitant alcohol intake may increase the risk of side effects such as dizziness and nausea. No specific food restrictions; however, fatty meals may delay absorption but do not affect overall exposure. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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 | 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. |
| Clinical Pearls | For acute alcohol withdrawal, nalmefene is administered as a single daily dose of 18 mg (as base) to reduce alcohol consumption. It is contraindicated in patients with severe hepatic impairment (Child-Pugh C) or end-stage renal disease (CrCl <30 mL/min). Coadministration with opioid agonists may precipitate withdrawal; avoid use in patients with known opioid dependence. Monitor liver function tests periodically due to potential hepatotoxicity. Nalmefene has no effect on the symptoms of acute alcohol intoxication. |
| Patient Advice | Take one tablet daily, preferably at the same time each day, with or without food. · Do not take this medication if you are currently using opioids or have recently used opioids (e.g., painkillers, heroin). · Avoid alcohol completely while starting this medication; after initial abstinence, aim to reduce consumption. · Common side effects include nausea, dizziness, insomnia, and headache; these often improve after the first week. · Inform your doctor if you have severe liver or kidney disease, or if you are pregnant or breastfeeding. · Do not drive or operate heavy machinery until you know how this medication affects you, as it may cause dizziness. |