Nalmefene

Oral
Adjunct in alcohol dependence

Severe (eGFR <30 mL/min/1.73 m²): Contraindicated.

Severe: Contraindicated.

Current or recent opioid addiction, acute opioid withdrawal symptoms, history of acute alcohol withdrawal syndrome. Severe hepatic and renal impairment. Concomitant use w/ opioid agonists (e.g. opioid analgesics, methadone) or partial agonists (e.g. buprenorphine).

Patient w/ psychiatric comorbidity (e.g. major depressive disorder), history of seizure disorders. Intended for use only to patient w/ high drinking risk level, at least 2 wk after assessment. Mild or moderate renal and hepatic impairment. Pregnancy and lactation.

Significant: Psychiatric symptoms, alcoholic psychosis, alcohol withdrawal symptoms.
Nervous: Dizziness, insomnia, headache, sleep disorder, confusional state, restlessness, somnolence, tremor, attention disturbance, paraesthesia, hypoaesthesia, fatigue, asthenia, malaise, abnormal feeling, hallucinations, dissociation.
CV: Tachycardia, palpitation.
GI: Nausea, decreased appetite, vomiting, dry mouth, diarrhoea.
Endocrine: Decreased libido, wt decreased.
Musculoskeletal: Muscle spasms.
Dermatologic: Hyperhidrosis.

This drug may cause dizziness and somnolence, if affected, do not drive or operate machinery.

Assess clinical status, alcohol dependence, level of alcohol consumption before initiation of therapy.

Increased exposure w/ UGT2B7 enzyme inhibitors (e.g. diclofenac, fluconazole). Decreased exposure w/ UGT2B7 enzyme inducers (e.g. dexamethasone, phenobarbital).
Potentially Fatal: Increased risk of resp depression w/ opioids (e.g. cough medications, opioid analgesics).

Description:
Mechanism of Action: Nalmefene is 6-methylene analogue of naltrexone, a specific opioid antagonist. It modifies cortico-mesolimbic functions of opioid receptors thereby reduces the level of alcohol consumption.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Bioavailability: Approx 40%. Time to peak plasma concentration: Approx 1.5 hr.
Distribution: Volume of distribution: Approx 3,200 L. Plasma protein binding: Approx 30%.
Metabolism: Undergoes rapid extensive first-pass metabolism in the liver into inactive nalmefene 3-O-glucuronide metabolite by UGT enzymes; small portion via sulfation into nalmefene 3-O-sulfate; and into nornalmefene by CYP enzymes and further converted to nornalmefene 3-O-glucuronide and nornalmefene 3-O-sulfate.
Excretion: Via urine (54%, as inactive metabolites); faeces (small amount). Terminal elimination half-life: Approx 12.5 hr.

Source: National Center for Biotechnology Information. PubChem Database. Nalmefene, CID=5284594, https://pubchem.ncbi.nlm.nih.gov/compound/Nalmefene (accessed on Jan. 22, 2020)

Store below 30°C.

Drugs Used in Substance Dependence

N07BB05 - nalmefene ; Belongs to the class of drugs used in the management of alcohol dependence.

Anon. Pharmacotherapy for Alcohol Use Disorder. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/10/2017.

Buckingham R (ed). Nalmefene. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 23/08/2017.

Joint Formulary Committee. Nalmefene. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 23/08/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Nalmefene Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 23/08/2017.