Nalmefene, sold under the brand nameRevex among others, is a medication that is used in the treatment ofopioid overdose andalcohol dependence.[2][3] Nalmefene belongs to the class ofopioid antagonists and can be takenby mouth, administered by injection, or delivered through nasal administration.[8]
Nalmefene is used in the European Union to reduce alcohol dependence[2] and NICE recommends the use of nalmefene to reducealcohol consumption in combination with psychological support for people who drink heavily.[11]
Based on a meta analysis, the usefulness of nalmefene for alcohol dependence is unclear.[12] Nalmefene, in combination with psychosocial management, may decrease the amount of alcohol drunk by people who are alcohol dependent.[12][13] The medication may also be taken "as needed", when a person feels the urge to consume alcohol.[13]
Nalmefene is structurally related to naltrexone and differs from it by substitution of theketone group at the C6 position of naltrexone with amethylene group (CH2). It binds to the MOR with similar affinity relative to naltrexone, but binds "somewhat more avidly" to the KOR and DOR in comparison.[15][19]
Nalmefene with a single 1 mg dose byintravenous injection has been found to produce brain MOR blockade of 99% at 5 minutes, 90% at 2 hours, 33% at 4 hours, and 10% at 8 hours.[23] A lower dose of 1 μg/kg intravenously resulted in brain MOR blockade of 52% at 5 minutes, 33% at 2 hours, 47% at 4 hours, and 26% at 8 hours.[23] Withoral administration, peak brain MOR occupancy of 87 to 100% was found after 3 hours with single or repeated dosing of nalmefene.[24][25] At 26 hours (1.1 days) post-administration, brain MOR occupancy was 83 to 100%; at 50 hours (2.1 days), it was 48 to 72%; and at 74 hours (3.1 days), it was 12 to 46%.[24][25] The half-time of nalmefene occupancy of brain MORs is about 29 hours and is much longer than withnaloxone.[24][26] Substantial brain MOR occupancy occurs with nalmefene even when blood levels of nalmefene are very low.[24][25] The prolonged brain MOR occupancy of nalmefene may be due to slow dissociation of nalmefene from MORs consequent to its high MOR affinity.[24][25]
Nalmefene is extensively metabolized in the liver, mainly by conjugation withglucuronic acid and also byN-dealkylation. Less than 5% of the dose is excreted unchanged. Theglucuronide metabolite is entirely inactive, while theN-dealkylated metabolite has minimal pharmacological activity.[citation needed]
In the United States, immediate-release injectable nalmefene was approved in 1995, as an antidote for opioid overdose.[29] It was sold under the brand name Revex.[3] The product was discontinued by its manufacturer around 2008.[30][31][32] A generic version was approved for medical use in the United States in February 2022.[10][33]
In May 2023, theFood and Drug Administration (FDA) approved a nalmefene hydrochloride nasal spray, under the brand nameOpvee, for the emergency treatment of opioid overdose in people aged twelve years of age and older.[8]
In August 2024, the FDA approved a nalmefene hydrochloride auto-injector (Zurnai) for the emergency treatment of known or suspected opioid overdose in people aged twelve years of age and older.[5][34] The FDA granted the application for the nalmefene hydrochloride auto-injectorfast track andpriority review designations.[34] The FDA granted approval of Zurnai to Purdue Pharma L.P.[34]
As of 2012, nalmefene inpill form, used for the treatment of alcohol dependence and other addictive behaviors, is not available in the United States.[9]
Danish pharmaceutical companyLundbeck has licensed nalmefene fromBiotie Therapies and performed clinical trials with nalmefene for treatment of alcohol dependence.[35] In 2011, they submitted an application for their medication named Selincro to theEuropean Medicines Agency.[36] The medication was authorized for use in the EU in March 2013.[37] and in October 2013, Scotland became the first country in the EU to prescribe the drug for alcohol dependence.[38] England followed Scotland by offering the medication as a treatment for problem drinking in October 2014.[39] In November 2014, nalmefene was approved as a possible treatment supplied by Britain'sNational Health Service (NHS) for reducing alcohol consumption in people with alcohol dependence.[40]
^abToll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications".NIDA Res Monogr.178:440–66.PMID9686407.
^Grosshans M, Mutschler J, Kiefer F (July 2015). "Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience".International Clinical Psychopharmacology.30 (4):237–8.doi:10.1097/YIC.0000000000000069.PMID25647453.
^abColasanti A, Lingford-Hughes A, Nutt D (2013). "Opioids Neuroimaging". In Miller PM (ed.).Biological Research on Addiction. Comprehensive Addictive Behaviors and Disorders. Vol. 2. Elsevier. pp. 675–687.doi:10.1016/B978-0-12-398335-0.00066-2.ISBN978-0-12-398335-0.
^Kim S, Wagner HN, Villemagne VL, Kao PF, Dannals RF, Ravert HT, et al. (November 1997). "Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by a dual-detector system".J Nucl Med.38 (11):1726–31.PMID9374341.
^"Nalmefene label"(PDF).U.S. Food and Drug Administration. Archived fromthe original(PDF) on 12 February 2022. Retrieved12 February 2022.
^"Baxter discontinues Revex injection".Monthly Prescribing Reference website. Haymarket Media, Inc. 9 July 2008.Archived from the original on 11 October 2016. Retrieved10 October 2016.
^Bidlack JM (2014). "Mixed Kappa/Mu Partial Opioid Agonists as Potential Treatments for Cocaine Dependence".Mixed κ/μ partial opioid agonists as potential treatments for cocaine dependence. Advances in Pharmacology. Vol. 69. Elsevier. pp. 387–418.doi:10.1016/B978-0-12-420118-7.00010-X.ISBN978-0-12-420118-7.PMID24484983.
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