This month’s offering was inspired a question posed by a 5th-year M.Pharm student after my presentation on Pharmaceutical Drug Misuse as part of the Trinity Addiction Pharmacy module, seeking my view on preventing opioid overdoses with Nalmefene. To say that my answer — “anything is worth trying” — was not up to scratch is putting it mildly, because when I went back over my answer, I quickly realised that I needed to find out a lot more about Nalmefene.
My woolly reply was due to the fact that my initial recall of Nalmefene related to its EMA-authorised use in reducing alcohol consumption in adult patients with alcohol dependence, rather than as an antagonist useful against opioid overdoses. Strangely, it is not licensed in the USA for alcohol or opioid use disorder, but in 2023
the Food and Drug Administration (FDA) did approve an intranasal spray containing Nalmefene called Opvee for the emergency treatment of known or suspected opioid overdose in adults and children aged 12 or over.
Because an IV formulation of the drug had been licensed by the FDA for reversal of opioid overdose in 1995, no new clinical data was required when intranasal (IN) Opvee was approved. Bioequivalence between the IV and IN formulations was assessed by pharmacokinetic studies in healthy volunteers, which were incorporated into a translational model along with receptor-binding affinity data, as set out in a 2024 paper in Frontiers in Psychiatry. The pharmacokinetic data was published in Clinical Pharmacology in Drug Development (2024), recording a half-life of 11 hours for Nalmefene compared to two hours for naloxone.
Nalmefene had five times the binding affinity of naloxone at three opioid receptors and this was reflected in its stronger and more rapid effect in reversing remifentanil-induced respiratory depression in healthy volunteers, as reported in a 2024 paper authored by employees of the company involved, that appeared in the Journal of Clinical Pharmacology.
The belief was that the longer half- life and greater antagonistic binding affinity made it superior to naloxone, particularly in overdoses involving the more potent synthetic opioids such as the fentanils and nitazenes now causing the majority of fatalities, especially in North America. For others however, that longer half-life was a cause of concern, in that it might cause a deep and protracted withdrawal syndrome. A 2024 commentary from the Departments of Pharmacy Practice and Medicine at the University of Illinois, published in the International Journal of Drug Policy, argued that data highlights that naloxone is the safe and effective standard of care in overdose. According to the authors, the data also supports the conclusion that Nalmefene may be unnecessary and may cause undue harm due to more severe and/or more prolonged withdrawal symptoms. Because those given Nalmefene may need longer periods of observation post antagonist treatment, this may add to the strain on Emergency Department and first responder resources. They called for more evidence before replacing naloxone with Nalmefene.
In response, a 2025 paper in Cureus, authored by staff from the manufacturers of Opvee, looked at post-marketing surveillance data for IN Nalmefene and concluded that the level of risk of precipitated withdrawal is low in real-world settings. The same journal carried another paper sponsored by the company describing a case report from Michigan concerning one individual given IN Nalmefene after an overdose of an unidentified opioid, whose oxygen saturation of up to 98 per cent was restored within 2.5 minutes without any precipitated withdrawal.
Worryingly for the company, a Position Statement from the American College of Medical Toxicology and
the American Academy of Clinical Toxicology was published in the Journal of Medical Toxicology in
2024, which stated unambiguously that Nalmefene should not replace naloxone as the primary opioid antidote at this time. It pointed out that the main adverse reaction to any opioid antagonist is acute withdrawal in those dependent on opioids, and that this ranges in severity from
mild dysphoria or GIT upset, to life- threatening conditions such as acute respiratory distress syndrome, severe agitation, dysrhythmias, and stress cardiomyopathy. It claimed that the pharmacokinetics of Nalmefene may result in a lengthened period of precipitated withdrawal compared to naloxone.
Responding to the claim that a stronger antagonist may be needed to cope with the current epidemic
of synthetic opioid overdoses, the Position Statement stated that “we are unable to find clinical evidence
that a strategy of repeated or escalating naloxone doses is inferior to Nalmefene in treating overdoses”. They expressed concern that IN Nalmefene has not been adequately studied in real-world settings and called for additional clinical and safety data, especially comparative studies with naloxone that included a thorough pharmacoeconomic evaluation. The Statement noted that naloxone should continue to be the preferred first-line agent until data supports the routine use of Nalmefene.
Now when I started preparing this article,, my working title was, ‘Is Nalmefene a viable alternative
to naloxone?’, so why the change to the past tense? The answer lies in a media report that the company that marketed Nalmefene had announced that they would no longer be marketing their buprenorphine- containing products (Suboxone and Subutex) in a number of countries, including Ireland and the UK. When I went to confirm this, I was linked online to their Third Quarter 2025 Financial Results, which confirmed
What is more worrying from an Irish perspective is that news about the buprenorphine products
the withdrawal of buprenorphine from
markets in Ireland, the UK, Sweden, Israel, Finland and Italy. To my surprise, that financial report also announced the discontinuation of the sales and marketing of Opvee. How much this decision was influenced by the Position Statement is hard to know. Equally, it might have been influenced by a Cease and Desist Order made against the company by the Attorney General of the State of New York, requiring it to stop marketing Opvee in that State on the basis that it had not been approved by authorities in New York, even though it had federal approval from the FDA.
What is more worrying from an Irish perspective is that news about the buprenorphine products. The Medical Independent of 24 November reported that 1,170 patients out of a total of 10,718 on Opioid Assisted Therapy (OAT) in Ireland were in receipt of buprenorphine as of the end of September. One can only hope that generic forms of this valuable drug for OAT will fill the void left by the proposed withdrawal of the branded products.
Dr Des Corrigan, Best Contribution in Pharmacy Award (winner), GSK Medical Media Awards 2014, is an Adjunct Associate Professor at the School of Pharmacy and Pharmaceutical Sciences at TCD where he was previously Director and won the Lifetime Achievement Award at the 2009 Pharmacist Awards.
He was chair of the Government’s National Advisory Committee on Drugs from 2000 to 2011, having previously chaired the Scientific and Risk Assessment Committees at the EU’s Drugs Agency in Lisbon. He chaired the Advisory Subcommittee on Herbal Medicines and was a member of the Advisory Committee on Human Medicines at the HPRA from 2007 to 2024. He has been a National Expert on Committee 13B (Phytochemistry) at the European Pharmacopoeia in Strasbourg and served on the editorial boards of a number of scientific journals on herbal medicine.
