219
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Nalmefene Hydrochloride: Potential Implications for Treating Alcohol and Opioid Use Disorder

, ORCID Icon & ORCID Icon
Pages 43-57 | Received 05 Dec 2023, Accepted 16 Mar 2024, Published online: 03 Apr 2024

References

  • Dydyk AM, Jain NK, Gupta M. Opioid use disorder. In: StatPearls [Internet]. StatPearls Publishing; 2022.
  • Taylor JL, Samet JH. Opioid use disorder. Ann Intern Med. 2022;175:ITC1–16.
  • Webster LR. Risk factors for opioid-use disorder and overdose. Anesth Analg. 2017;125(5):1741–1748. doi:10.1213/ANE.0000000000002496
  • Haley DF, Saitz R. The opioid epidemic during the COVID-19 pandemic. JAMA. 2020;324:1615–1617. doi:10.1001/jama.2020.18543
  • Rinaldi R, Bersani G, Marinelli E, Zaami S. The rise of new psychoactive substances and psychiatric implications: a wide-ranging, multifaceted challenge that needs far‐reaching common legislative strategies. Hum Psychopharmacol Clin Exp. 2020;35:e2727.
  • Pichini S, Zaami S, Pacifici R, Tagliabracci A, Busardò FP. The challenge posed by new synthetic opioids: pharmacology and toxicology. Front Pharmacol. 2019;563. doi:10.3389/fphar.2019.00563
  • Lo Faro AF, Berardinelli D, Cassano T, et al. New psychoactive substances intoxications and fatalities during the COVID-19 epidemic. Biology. 2023;12:273. doi:10.3390/biology12020273
  • Amaducci A, Aldy K, Campleman SL, et al. Naloxone use in novel potent opioid and fentanyl overdoses in emergency department patients. JAMA Network Open. 2023;6(8):e2331264–e2331264. doi:10.1001/jamanetworkopen.2023.31264
  • Coffa D, Snyder H. Opioid use disorder: medical treatment options. Am Fam Physician. 2019;100:416–425.
  • Yarmolinsky A, Rettig RA. Federal regulation of methadone treatment; 1995.
  • Herman BH, Vocci F, Bridge P. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Neuropsychopharmacology. 1995;13:269–293. doi:10.1016/0893-133X(95)00140-9
  • Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009. doi:10.1002/14651858.CD002209.pub2
  • Shulman M, Wai JM, Nunes EV. Buprenorphine treatment for opioid use disorder: an overview. CNS Drugs. 2019;33(6):567–580. doi:10.1007/s40263-019-00637-z
  • Pinto H, Maskrey V, Swift L, Rumball D, Wagle A, Holland R. The SUMMIT trial:: a field comparison of buprenorphine versus methadone maintenance treatment. J Subst Abuse Treat. 2010;39(4):340–352. doi:10.1016/j.jsat.2010.07.009
  • Alderks CE. Trends in the use of methadone, buprenorphine, and extended-release naltrexone at substance abuse treatment facilities: 2003–2015 (update); 2017.
  • Feng H, Elladki R, Jiang J, Wei G-W. Machine-learning analysis of opioid use disorder informed by MOR, DOR, KOR, NOR and ZOR-based interactome networks. Comput Biol Med. 2023;157:106745. doi:10.1016/j.compbiomed.2023.106745
  • Younger J, Noor N, McCue R, Mackey S. Low‐dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double‐blind, placebo‐controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013;65:529–538. doi:10.1002/art.37734
  • Mammen K, Bell J. The clinical efficacy and abuse potential of combination buprenorphine–naloxone in the treatment of opioid dependence. Expert Opin Pharmacother. 2009;10(15):2537–2544. doi:10.1517/14656560903213405
  • Strang J, McDonald R, Campbell G, et al. Take-home naloxone for the emergency interim management of opioid overdose: the public health application of an emergency medicine. Drugs. 2019;79(13):1395–1418. doi:10.1007/s40265-019-01154-5
  • NIDA. How much does opioid treatment cost? 2023. Available from: https://nida.nih.gov/publications/research-reports/medications-to-treat-opioid-addiction/how-much-does-opioid-treatment-cost. Accessed March 19, 2024.
  • Goldfine CE, Tom JJ, Im DD, et al. The therapeutic use and efficacy of ketamine in alcohol use disorder and alcohol withdrawal syndrome: a scoping review. Front Psychiatry. 2023;14:1141836. doi:10.3389/fpsyt.2023.1141836
  • Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311(18):1889–1900. doi:10.1001/jama.2014.3628
  • Fan AZ, Chou SP, Zhang H, Jung J, Grant BF. Prevalence and correlates of past-year recovery from DSM-5 alcohol use disorder: results from national epidemiologic survey on alcohol and related conditions-III. Alcohol Clin Exp Res. 2019;43:2406–2420. doi:10.1111/acer.14192
  • Zindel LR, Kranzler HR. Pharmacotherapy of alcohol use disorders: seventy-five years of progress. J Stud Alcohol Drugs Suppl. 2014;79–88. doi:10.15288/jsads.2014.s17.79
  • Grosshans M, Mutschler J, Kiefer F. Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience. Int Clin Psychopharmacol. 2015;30(4):237–238. doi:10.1097/YIC.0000000000000069
  • Wang DS, Sternbach G, Varon J. Nalmefene: a long-acting opioid antagonist. Clinical applications in emergency medicine. J Emerg Med. 1998;16(3):471–475. doi:10.1016/S0736-4679(98)00019-5
  • Grant JE, Potenza MN, Hollander E, et al. Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry. 2006;163(2):303–312. doi:10.1176/appi.ajp.163.2.303
  • Dhawan BN, Cesselin F, Raghubir R, et al. International Union of Pharmacology. XII. Classification of opioid receptors. Pharmacol Rev. 1996;48(4):567–592.
  • Potter DN, Damez-Werno D, Carlezon WA Jr, Cohen BM, Chartoff EH. Repeated exposure to the κ-opioid receptor agonist salvinorin A modulates extracellular signal-regulated kinase and reward sensitivity. Biol Psychiatry. 2011;70(8):744–753. doi:10.1016/j.biopsych.2011.05.021
  • Knoll AT, Carlezon WA Jr. Dynorphin, stress, and depression. Brain Res. 2010;1314:56–73. doi:10.1016/j.brainres.2009.09.074
  • Woods JH, Medzihradsky F, Smith CB, Butelman ER, Winger G. Evaluation of new compounds for opioid activity (1996). Probl Drug Depend. 1997;396:1.
  • Wang D, Raehal KM, Bilsky EJ, Sadée W. Inverse agonists and neutral antagonists at µ opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence. J Neurochem. 2001;77:1590–1600. doi:10.1046/j.1471-4159.2001.00362.x
  • Kyhl LB, Li S, Faerch KU, Soegaard B, Larsen F, Areberg J. Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ‐opioid receptor occupancy. Br J Clin Pharmacol. 2016;81:290–300. doi:10.1111/bcp.12805
  • Lee MC, Wagner HN, Tanada S, Frost JJ, Bice AN, Dannals RF. Duration of occupancy of opiate receptors by naltrexone. J Nucl Med. 1988;29:1207–1211.
  • Rabiner EA, Beaver J, Makwana A, et al. Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans. Mol Psychiatry. 2011;16(8):826–835. doi:10.1038/mp.2011.29
  • Walker BM, Koob GF. Pharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence. Neuropsychopharmacology. 2008;33(3):643–652. doi:10.1038/sj.npp.1301438
  • Schluger JH, Ho A, Borg L, et al. Nalmefene causes greater hypothalamic‐pituitary‐adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism. Alcohol Clin Exp Res. 1998;22:1430–1436. doi:10.1111/j.1530-0277.1998.tb03931.x
  • Jacobson ML, Browne CA, Lucki I. Kappa opioid receptor antagonists as potential therapeutics for stress-related disorders. Annu Rev Pharmacol Toxicol. 2020;60(1):615–636. doi:10.1146/annurev-pharmtox-010919-023317
  • Benth JŠ, Solli KK, Opheim A, et al. Anxiety, depression, and insomnia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone: a randomized clinical trial and follow-up study. JAMA Psychiatry. 2019;76:127–134. doi:10.1001/jamapsychiatry.2018.3537
  • Hao S, Ogawa H. Naltrexone, but not atropine or yohimbine, antagonizes suppression of formalin-induced spinal sensitization by intrathecal nociceptin. Life Sci. 1998;63(11):A167–73. doi:10.1016/S0024-3205(98)00359-2
  • Meeting C on P of DD (U. S). S, Abuse NI on D. Problems of Drug Dependence: proceedings of the. Annual Scientific Meeting, the College on Problems of Drug Dependence, Inc [Internet]. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Drug Abuse; 1997. Available from: https://books.google.com/books?id=hgj5eTyGTI4C. Accessed March 19, 2024.
  • Johansen KGV, Tarp S, Astrup A, Lund H, Pagsberg AK, Christensen R. Harms associated with taking nalmefene for substance use and impulse control disorders: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2017;12:e0183821.
  • Gual A, He Y, Torup L, van den Brink W, Mann K; Group E 2 S. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol. 2013;23(11):1432–1442. doi:10.1016/j.euroneuro.2013.02.006
  • Mann K, Bladström A, Torup L, Gual A, van den Brink W. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry. 2013;73(8):706–713. doi:10.1016/j.biopsych.2012.10.020
  • van den Brink W, Sørensen P, Torup L, Mann K, Gual A, Group SS. Long-term efficacy, tolerability and safety of nalmefene as-needed in patients with alcohol dependence: a 1-year, randomised controlled study. J Psychopharmacol. 2014;28:733–744. doi:10.1177/0269881114527362
  • Kaplan JL, Marx JA. Effectiveness and safety of intravenous nalmefene for emergency department patients with suspected narcotic overdose: a pilot study. Ann Emerg Med. 1993;22(2):187–190. doi:10.1016/S0196-0644(05)80200-8
  • Sarkar S, Addagadda SS, Bhatia G, Chadda RK. Adverse drug reactions with naltrexone: experience from an addiction treatment center. Indian J Psychiatry. 2021;63(2):206–207. doi:10.4103/psychiatry.IndianJPsychiatry_94_20
  • Hoofnagle JH. LiverTox: a website on drug-induced liver injury. In: Drug-induced liver disease. Elsevier. 2013;725–732.
  • Niciu MJ, Arias AJ. Targeted opioid receptor antagonists in the treatment of alcohol use disorders. CNS Drugs. 2013;27(10):777–787. doi:10.1007/s40263-013-0096-4
  • Kristensen K, Christensen CB, Christrup LL. The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Life Sci. 1994;56(2):45–50. doi:10.1016/0024-3205(94)00937-6
  • Wang S. Historical review: opiate addiction and opioid receptors. Cell Transplant. 2019;28:233–238. doi:10.1177/0963689718811060
  • Walwyn WM, Miotto KA, Evans CJ. Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions. Drug Alcohol Depend. 2010;108(3):156–165. doi:10.1016/j.drugalcdep.2010.01.001
  • Gelfman LP, Chai EJ. Chapter 8 - What Special Considerations Should Guide the Safe Use of Methadone? In: Goldstein NE, Morrison RS, editors. Evidence-Based Practice in Palliative Medicine [Internet]. Philadelphia: W.B. Saunders; 2013:39–43.
  • Davis MP. Methadone does not block NMDA receptors. J Pain Symptom Manage. 2021;62(3):e7–8. doi:10.1016/j.jpainsymman.2021.05.014
  • Toce MS, Chai PR, Burns MM, Boyer EW. Pharmacologic treatment of opioid use disorder: a review of pharmacotherapy, adjuncts, and toxicity. J Med Toxicol. 2018;14(4):306–322. doi:10.1007/s13181-018-0685-1
  • Yokell M A, Zaller N D, Green T C, Rich J D. Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: an international review. Curr Drug Abuse Rev. 2011;4:28–41. doi:10.2174/1874473711104010028
  • Serafini G, Adavastro G, Canepa G, et al. The efficacy of buprenorphine in major depression, treatment-resistant depression and suicidal behavior: a systematic review. Int J Mol Sci. 2018;19(8):2410. doi:10.3390/ijms19082410
  • Pande LJ, Arnet RE, Piper BJ. An examination of the complex pharmacological properties of the non-selective opioid modulator buprenorphine. Pharmaceuticals. 2023;16(10):1397. doi:10.3390/ph16101397
  • Canestrelli C, Marie N, Noble F. Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration. Int J Neuropsychopharmacol. 2014;17:1367–1373. doi:10.1017/S146114571400025X
  • Comer SD, Sullivan MA, Vosburg SK, et al. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine‐maintained intravenous heroin abusers. Addiction. 2010;105:709–718. doi:10.1111/j.1360-0443.2009.02843.x
  • Rahimi‐Movaghar A, Gholami J, Amato L, Hoseinie L, Yousefi‐Nooraie R, Amin‐Esmaeili M. Pharmacological therapies for management of opium withdrawal. Cochrane Database Syst Rev. 2018. doi:10.1002/14651858.CD007522.pub2
  • Whelan PJ, Remski K. Buprenorphine vs methadone treatment: a review of evidence in both developed and developing worlds. J Neurosci Rural Pract. 2012;3:45–50. doi:10.4103/0976-3147.91934
  • VIVITROL XR [package insert]. Alkermes Inc. 2021.
  • Kumar R, Viswanath O, Saadabadi A. Buprenorphine; 2017.
  • BUTRANS [package insert]. Purdue Pharma LP; 2014.
  • BUPRENEX [package insert]. Indivior Inc.; 2019.
  • BELBUCA [package insert]. Ende Pharmaceuticals Inc.; 2015.
  • Kleppner SR, Patel R, Costantini LC, McDonough J. In-vitro and in-vivo characterization of a buprenorphine delivery system. J Pharm Pharmacol. 2006;58:295–302. doi:10.1211/jpp.58.3.0002
  • Moody DE, Slawson MH, Strain EC, Laycock JD, Spanbauer AC, Foltz RL. A liquid chromatographic-electrospray ionization-tandem mass spectrometric method for determination of buprenorphine, its metabolite, norbuprenorphine, and a coformulant, naloxone, that is suitable for in vivo and in vitro metabolism studies. Anal Biochem. 2002;306(1):31–39. doi:10.1006/abio.2002.5673
  • Brown SM, Holtzman M, Kim T, Kharasch ED. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active. J Am Soc Anesthesiologists. 2011;115:1251–1260.
  • Ohtani M, Kotaki H, Sawada Y, Iga T. Comparative analysis of buprenorphine-and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther. 1995;272:505–510.
  • SUBLOCADE [package insert]. Indivior Inc.; 2017.
  • BRIXADI [package insert]. Braeburn Inc.; 2023.
  • SUBUTEX [package insert]. Reckitt Benckiser Pharmaceuticals Inc; 2011.
  • BUPRENORPHINE SUBLINGUAL TABLETS [package insert]. Sun Pharmaceutical Industries Inc; 2023.
  • PROBUPHINE [package insert]. Braeburn Pharmaceuticals, Inc; 2016.
  • Barnwal P, Das S, Mondal S, Ramasamy A, Maiti T, Saha A. Probuphine®(buprenorphine implant): a promising candidate in opioid dependence. Ther Adv Psychopharmacol. 2017;7:119–134. doi:10.1177/2045125316681984
  • Bullingham RES, McQuay HJ, Moore A, Bennett MRD. Buprenorphine kinetics. Clin Pharmacol Ther. 1980;28:667–672. doi:10.1038/clpt.1980.219
  • Huestis MA, Cone EJ, Pirnay SO, Umbricht A, Preston KL. Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans. Drug Alcohol Depend. 2013;131(3):258–262. doi:10.1016/j.drugalcdep.2012.11.014
  • SUBOXONE [package insert]. Indivior Inc; 2022.
  • IONSYS [package insert]. Ortho McNeil Inc; 2006.
  • Vasisht N, Gever LN, Tagarro I, Finn AL. Single-dose pharmacokinetics of fentanyl buccal soluble film. Pain Med. 2010;11(7):1017–1023. doi:10.1111/j.1526-4637.2010.00875.x
  • Abstral [package insert]. Sentynl Therapeutics Inc; 2016.
  • ONSOLIS [package insert]. Meda Pharmaceuticals Inc; 2011.
  • FENTORA [package insert]. Cephalon Inc; 2011.
  • SUBSYS [package insert]. Insys Therapeutics Inc; 2016.
  • Actiq [package insert]. Abbott Laboratories; 1998.
  • DURAGESIC [package insert]. Janssen Pharmaceuticals Inc; 2021.
  • Inturrisi CE, Colburn WA, Kaiko RF, Houde RW, Foley KM. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther. 1987;41(4):392–401. doi:10.1038/clpt.1987.47
  • Horst J, Frei‐Jones M, Deych E, Shannon W, Kharasch ED. Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease. Pediatr Blood Cancer. 2016;63(12):2123–2130. doi:10.1002/pbc.26207
  • DOLOPHINE [package insert]. Roxane Laboratories; 2014.
  • METHADOSE [package insert]. Mallinckrodt Inc; 2016.
  • Hain RDW. Morphine and morphine‐6‐glucuronide in the plasma and cerebrospinal fluid of children. Br J Clin Pharmacol. 1999;48(1):37–42. doi:10.1046/j.1365-2125.1999.00948.x
  • DURAMORPH [package insert]. Baxter Healthcare Corporation; 2007.
  • MORPHINE SULFATE TABLETS [package insert]. West-Ward Pharmaceuticals Corp; 2021.
  • KADIAN [package insert]. Allergan USA Inc; 2016.
  • MS CONTIN [package insert]. Purdue Pharma LP; 2016.
  • Booij LHDJ, Vree TB, Koppers-Hoyset H, Lagerwerf AJ. Explorative pharmacokinetic study of preoperative administration of morphine 50mg sustained-release capsules (KapanolTM to surgical patients. Clin Drug Investig. 1999;18:125–132. doi:10.2165/00044011-199918020-00005
  • NALMEFENE HYDROCHLORIDE [package insert]. Purdue Pharma LP; 2022.
  • SELINCRO [package insert]. Elaiapharm; 2017.
  • REVIA [package insert]. Duramed Pharmaceuticals Inc; 2013.
  • Dunbar JL, Turncliff RZ, Dong Q, Silverman BL, Ehrich EW, Lasseter KC. Single-and multiple-dose pharmacokinetics of long‐acting injectable naltrexone. Alcohol Clin Exp Res. 2006;30:480–490. doi:10.1111/j.1530-0277.2006.00052.x
  • Meyer MC, Straughn AB, Lo MW, Schary WL, Whitney CC. Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry. 1984;45:15–19.
  • Dale OLA, Hoffer C, Sheffels P, Kharasch ED. Disposition of nasal, intravenous, and oral methadone in healthy volunteers. Clin Pharmacol Ther. 2002;72:536–545. doi:10.1067/mcp.2002.128386
  • Kharasch ED, Hoffer C, Whittington D, Sheffels P. Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther. 2004;76:250–269. doi:10.1016/j.clpt.2004.05.003
  • Dennis BB, Bawor M, Thabane L, Sohani Z, Samaan Z, Zhang H. Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: a systematic review and meta-analysis. PLoS One. 2014;9(1):e86114. doi:10.1371/journal.pone.0086114
  • Verebey K, Volavka J, Mule SJ, Resnick RB. Naltrexone: disposition, metabolism, and effects after acute and chronic dosing. Clin Pharmacol Ther. 1976;20(3):315–328. doi:10.1002/cpt1976203315
  • Mitchell MC Jr, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs. 2012;73(6):991–997. doi:10.15288/jsad.2012.73.991
  • Matzke GR, Frye RF, Alexander ACM, et al. The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene. J Clin Pharmacol. 1996;36:144–151. doi:10.1002/j.1552-4604.1996.tb04179.x
  • Lucchi L, Bosio A, Spano PF, Trabucchi M. Action of ethanol and salsolinol on opiate receptor function. Brain Res. 1982;232:506–510. doi:10.1016/0006-8993(82)90297-9
  • Hiller JM, Angel LM, Simon EJ. Multiple opiate receptors: alcohol selectively inhibits binding to delta receptors. Science. 1981;214(4519):468–469. doi:10.1126/science.6270788
  • Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992;49:876–880. doi:10.1001/archpsyc.1992.01820110040006
  • O’malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry. 1992;49:881–887. doi:10.1001/archpsyc.1992.01820110045007
  • Soyka M. Nalmefene for the treatment of alcohol use disorders: recent data and clinical potential. Expert Opin Pharmacother. 2016;17(4):619–626. doi:10.1517/14656566.2016.1146689
  • Kissler JL, Sirohi S, Reis DJ, et al. The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors. Biol Psychiatry. 2014;75(10):774–782. doi:10.1016/j.biopsych.2013.03.014
  • Nealey KA, Smith AW, Davis SM, Smith DG, Walker BM. κ-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology. 2011;61(1–2):35–42. doi:10.1016/j.neuropharm.2011.02.012
  • Ingman K, Hagelberg N, Aalto S, et al. Prolonged central μ-opioid receptor occupancy after single and repeated nalmefene dosing. Neuropsychopharmacology. 2005;30(12):2245–2253. doi:10.1038/sj.npp.1300790
  • Tadori Y. Pharmacological profile and clinical findings of nalmefene (Selincro®) for reducing alcohol consumption in patients with alcohol dependence. Nihon Yakurigaku Zasshi. 2020;155(2):113–119. doi:10.1254/fpj.19136
  • van den Brink W, Strang J, Gual A, Sørensen P, Jensen TJ, Mann K. Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme. Expert Opin Drug Saf. 2015;14(4):495–504. doi:10.1517/14740338.2015.1011619
  • Naudet F, Fitzgerald N, Braillon A. Nalmefene for alcohol dependence: a NICE decision? Lancet Psychiatry. 2016;3(12):1104–1105. doi:10.1016/S2215-0366(16)30356-X
  • Bachmutsky I, Wei XP, Kish E, Yackle K. Opioids depress breathing through two small brainstem sites. Elife. 2020;9:e52694. doi:10.7554/eLife.52694
  • Hill R, Santhakumar R, Dewey W, Kelly E, Henderson G. Fentanyl depression of respiration: comparison with heroin and morphine. Br J Pharmacol. 2020;177(2):254–265. doi:10.1111/bph.14860
  • Yong Z, Gao X, Ma W, Dong H, Gong Z, Su R. Nalmefene reverses carfentanil-induced loss of righting reflex and respiratory depression in rats. Eur J Pharmacol. 2014;738:153–157. doi:10.1016/j.ejphar.2014.05.044
  • Kaplan JL, Marx JA, Calabro JJ, et al. Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. Ann Emerg Med. 1999;34(1):42–50. doi:10.1016/S0196-0644(99)70270-2
  • Britch SC, Walsh SL. Treatment of opioid overdose: current approaches and recent advances. Psychopharmacology. 2022;239(7):2063–2081. doi:10.1007/s00213-022-06125-5
  • Purdue Pharma LP. Purdue pharma introduces nalmefene HCl injection, 2mg/2mL (1mg/1mL) in the U.S. for the treatment of known or suspected overdose with natural or synthetic opioids; 2022.
  • NARCAN [package insert]. Adapt Pharma Inc; 2015.
  • Krieter P, Chiang CN, Gyaw S, Skolnick P, Snyder R. Pharmacokinetic interaction between naloxone and naltrexone following intranasal administration to healthy subjects. Drug Metab Dispos. 2019;47(7):690–698. doi:10.1124/dmd.118.085977
  • United States Food and Drug Administration. FDA Approves Prescription Nasal Spray to Reverse Opioid Overdose. United States Food and Drug Administration; 2023.
  • OPVEE [package insert]. Opiant Pharm. 2023.
  • Crystal R, Ellison M, Purdon C, Skolnick P. Pharmacokinetic properties of an FDA‐approved intranasal nalmefene formulation for the treatment of opioid overdose. Clin Pharmacol Drug Dev. 2023;13(1):58–69. doi:10.1002/cpdd.1312
  • Krieter P, Gyaw S, Crystal R, Skolnick P. Fighting fire with fire: development of intranasal nalmefene to treat synthetic opioid overdose. J Pharmacol Exp Ther. 2019;371(2):409–415. doi:10.1124/jpet.118.256115
  • Jia Z, Chen Y, Gao T, et al. Nalmefene vs. dexmedetomidine for prevention of postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery with remifentanil infusion: a randomized double-blind controlled trial. Front Pharmacol. 2023;14:1131812. doi:10.3389/fphar.2023.1131812
  • Grant JE, Odlaug BL, Potenza MN, Hollander E, Kim SW. Nalmefene in the treatment of pathological gambling: multicentre, double-blind, placebo-controlled study. Br J Psychiatry. 2010;197(4):330–331. doi:10.1192/bjp.bp.110.078105
  • Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011;68:1238–1246. doi:10.1001/archgenpsychiatry.2011.121
  • Frost MC, Zhang L, Kim HM, Lin L. Use of and retention on video, telephone, and in-person buprenorphine treatment for opioid use disorder during the COVID-19 pandemic. JAMA Network Open. 2022;5(10):e2236298–e2236298. doi:10.1001/jamanetworkopen.2022.36298
  • Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2014(2). doi:10.1002/14651858.CD002207.pub4
  • Bell J, Trinh L, Butler B, Randall D, Rubin G. Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. Addiction. 2009;104(7):1193–1200. doi:10.1111/j.1360-0443.2009.02627.x
  • Mégarbane B, Hreiche R, Pirnay S, Marie N, Baud FJ. Does high-dose buprenorphine cause respiratory depression? Possible mechanisms and therapeutic consequences. Toxicol Rev. 2006;25:79–85. doi:10.2165/00139709-200625020-00002
  • White J, Bell J, Saunders JB, et al. Open-label dose-finding trial of buprenorphine implants (Probuphine)® for treatment of heroin dependence. Drug Alcohol Depend. 2009;103(1–2):37–43. doi:10.1016/j.drugalcdep.2009.03.008
  • Jarvis BP, Holtyn AF, DeFulio A, et al. Effects of incentives for naltrexone adherence on opiate abstinence in heroin‐dependent adults. Addiction. 2017;112:830–837. doi:10.1111/add.13724
  • Jones HE, Johnson RE, Fudala PJ, Henningfield JE, Heishman SJ. Nalmefene: blockade of intravenous morphine challenge effects in opioid abusing humans. Drug Alcohol Depend. 2000;60(1):29–37. doi:10.1016/S0376-8716(00)80005-8