Nalmefene is available as a generic medication.[9]
Medical usesedit
Opioid overdoseedit
Intravenous doses of nalmefene have been shown effective at counteracting the respiratory depression produced by opioid overdose.[3]
Alcohol dependenceedit
Nalmefene is used in the European Union to reduce alcohol dependence[2] and NICE recommends the use of nalmefene to reduce alcohol consumption in combination with psychological support for people who drink heavily.[10]
Based on a meta analysis, the usefulness of nalmefene for alcohol dependence is unclear.[11] Nalmefene, in combination with psychosocial management, may decrease the amount of alcohol drunk by people who are alcohol dependent.[11][12] The medication may also be taken "as needed", when a person feels the urge to consume alcohol.[12]
Side effectsedit
Very commonedit
The following side effects of nalmefene are very common (≥10% incidence):
Insomnia
Dizziness
Headache
Nausea
Commonedit
The following side effects of nalmefene are common (≥1% to <10% incidence):
Decreased appetite
Sleep disorder
Confusional state
Restlessness
Libido decreased (including loss of libido)
Somnolence
Tremor
Disturbance in attention
Paraesthesia
Hypoaesthesia
Tachycardia
Palpitations
Vomiting
Dry mouth
Diarrhea
Hyperhidrosis
Muscle spasms
Fatigue
Asthenia
Malaise
Feeling abnormal
Weight decreased
The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration.[13]
Nalmefene is structurally related to naltrexone and differs from it by substitution of the ketone group at the C6 position of naltrexone with a methylene 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.[14][18]
Nalmefene with a single 1 mg dose by intravenous 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.[22] 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.[22] With oral administration, peak brain MOR occupancy of 87 to 100% was found after 3 hours with single or repeated dosing of nalmefene.[23][24] 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%.[23][24] The half-time of nalmefene occupancy of brain MORs is about 29 hours and is much longer than with naloxone.[23][25] Substantial brain MOR occupancy occurs with nalmefene even when blood levels of nalmefene are very low.[23][24] The prolonged brain MOR occupancy of nalmefene may be due to slow dissociation of nalmefene from MORs consequent to its high MOR affinity.[23][24]
Metabolismedit
Nalmefene is extensively metabolized in the liver, mainly by conjugation with glucuronic acid and also by N-dealkylation. Less than 5% of the dose is excreted unchanged. The glucuronide metabolite is entirely inactive, while the N-dealkylated metabolite has minimal pharmacological activity.[citation needed]
Chemistryedit
Nalmefene is a derivative of naltrexone and was first reported in 1975.[26]
Society and cultureedit
Nalmefene was first reported in a patent in 1974.[27]
United Statesedit
In the United States, immediate-release injectable nalmefene was approved in 1995, as an antidote for opioid overdose.[28] It was sold under the brand name Revex.[3] The product was discontinued by its manufacturer around 2008.[29][30][31] A generic version was approved for medical use in the United States in February 2022.[9][32]
In May 2023, the FDA approved a nalmefene hydrochloride nasal spray, under the brand name Opvee, for the emergency treatment of opioid overdose in people twelve years of age and older.[33]
Nalmefene in pill form, which is used to treat alcohol dependence and other addictive behaviors, is not available in the United States.[8]
European Unionedit
Danish pharmaceutical company Lundbeck has licensed nalmefene from Biotie Therapies and performed clinical trials with nalmefene for treatment of alcohol dependence.[34] In 2011, they submitted an application for their drug termed Selincro to the European Medicines Agency.[35] The drug was approved for use in the EU in March 2013.[36] and in October 2013, Scotland became the first country in the EU to prescribe the drug for alcohol dependence.[37] England followed Scotland by offering the substance as a treatment for problem drinking in October 2014.[38] In November 2014, nalmefene was approved as a possible treatment supplied by Britain's National Health Service (NHS) for reducing alcohol consumption in people with alcohol dependence.[39]
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^ abc"Selincro 18mg film-coated tablets". UK Electronic Medicines Compendium. September 2016. Archived from the original on 27 April 2021. Retrieved 13 June 2017.
^ abcd"Revex- nalmefene hydrochloride injection, solution". DailyMed. Archived from the original on 21 January 2022. Retrieved 11 February 2022.
^"Opvee- nalmefene hydrochloride spray". DailyMed. 19 June 2023. Retrieved 25 June 2023.
^"Selincro EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 11 February 2022. Retrieved 11 February 2022.
^Kyhl LE, Li S, Faerch KU, Soegaard B, Larsen F, Areberg J (February 2016). "Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy". British Journal of Clinical Pharmacology. 81 (2). Wiley: 290–300. doi:10.1111/bcp.12805. PMC4833148. PMID 26483076.
^"FDA Approves Prescription Nasal Spray to Reverse Opioid Overdose". U.S. Food and Drug Administration (FDA) (Press release). 23 May 2023. Retrieved 1 June 2023.
^ ab"Nalmefene". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Library of Medicine. 24 March 2020. PMID 31643618. Bookshelf ID: NBK548295. Archived from the original on 13 November 2021. Retrieved 12 February 2022.
^ ab"Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 11 February 2022. Archived from the original on 12 February 2022. Retrieved 11 February 2022.
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^ abPalpacuer C, Laviolle B, Boussageon R, Reymann JM, Bellissant E, Naudet F (December 2015). "Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials". PLOS Medicine. 12 (12): e1001924. doi:10.1371/journal.pmed.1001924. PMC4687857. PMID 26694529.
^ abPaille F, Martini H (2014). "Nalmefene: a new approach to the treatment of alcohol dependence". Substance Abuse and Rehabilitation. 5 (5): 87–94. doi:10.2147/sar.s45666. PMC4133028. PMID 25187751.
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^ abcLinda P. Dwoskin (29 January 2014). Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Elsevier Science. pp. 398–. ISBN 978-0-12-420177-4. Archived from the original on 10 January 2023. Retrieved 31 October 2016.
^ abToll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS (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. PMID 9686407.
^ abClark SD, Abi-Dargham A (October 2019). "The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence". Biol Psychiatry. 86 (7): 502–511. doi:10.1016/j.biopsych.2019.05.012. PMID 31376930. S2CID 162168648.
^ abNiciu MJ, Arias AJ (October 2013). "Targeted opioid receptor antagonists in the treatment of alcohol use disorders". CNS Drugs. 27 (10): 777–87. doi:10.1007/s40263-013-0096-4. PMC4600601. PMID 23881605.
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^ 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. ISBN 9780123983350.
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^ abcdIngman K, Hagelberg N, Aalto S, Någren K, Juhakoski A, Karhuvaara S, Kallio A, Oikonen V, Hietala J, Scheinin H (December 2005). "Prolonged central mu-opioid receptor occupancy after single and repeated nalmefene dosing". Neuropsychopharmacology. 30 (12): 2245–53. doi:10.1038/sj.npp.1300790. PMID 15956985. S2CID 2453226.
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^"Determination That Revex (Nalmefene Hydrochloride Injection), 0.1 Milligram Base/Milliliter and 1.0 Milligram Base/Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness". Federal Register. 3 November 2017. Archived from the original on 28 January 2022. Retrieved 11 February 2022.
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^Clinical trial number NCT00811720 for "Efficacy of nalmefene in patients with alcohol dependence (ESENSE1" at ClinicalTrials.gov
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