A paper published this month in the journal Current Addiction Reports discusses the merits of intranasal medications that can reverse overdoses of high-potency synthetic opioids (HPSOs) such as fentanyl.
Indivior funded the manuscript, which was based on the results of last summer’s Reversing Synthetic Opioid Overdose (RESPIRE) Expert Forum—also funded by the addiction-focused pharma—that brought together eight leaders representing emergency medicine, pharmacy, state health agencies, Indian Health Services, addiction research and forensic science.
The company makes Opvee, an opioid overdose reversal medication that aligns with the expert panel’s recommendations.
“Indivior is committed to partnering closely with healthcare providers, policymakers, and communities to ensure that advanced overdose reversal solutions reach those who need them most, especially as HPSOs drive unprecedented risks and challenges,” Christian Heidbreder, Ph.D., the company’s chief scientific officer, said in a statement.
The paper’s publication came shortly before National Fentanyl Awareness Day, observed every year on April 29. Fentanyl and other synthetic opioids were involved in more than 90% of opioid overdose fatalities in the year preceding the July forum, according to the report.
Indivior is the maker of several treatments for opioid use disorder, as well as Opvee, which in May 2023 earned the first FDA approval for a nasal spray version of active ingredient nalmefene.
Naloxone is the current standard of care for treating opioid overdoses and is more widely available than nalmefene—helped along by its first over-the-counter FDA approval for Emergent BioSolutions’ 4 mg Narcan in early 2023. The new paper’s authors, however, suggest that nalmefene may be more effective in treating some overdoses, especially those involving HPSOs.
The most crucial aspects of medications used to treat overdoses of synthetic opioids are rapid onset, long duration and high potency, according to the authors.
Nalmefene outpaces naloxone on all three of those aspects: Data cited in the paper show that nalmefene has a higher opioid receptor affinity than naloxone. And, while naloxone reaches peak blood concentration in 30 minutes and has a circulating half-life of about two hours, nalmefene’s time to peak is 15 minutes and its half-life is longer than 11 hours, which may make it “particularly well-suited for reversing HPSO overdose,” they wrote.
The experts also pointed to a model predicting that a single 4 mg dose of naloxone would reduce the likelihood of cardiac arrest following a fentanyl overdose from about 78% to 47%, while a single 3-mg dose of nalmefene would bring it down to 11.6%.
Previous expert publications, including a September 2023 joint release (PDF) from the American College of Medical Toxicology and the American Academy of Clinical Toxicology, have suggested that more research is needed into the risks and benefits of nalmefene, as its longer duration of action could potentially lead to a longer period of the opioid withdrawal symptoms that are the primary adverse effect of all reversal meds.
That longer duration may also create a “false sense of comfort that no further care is needed,” possibly leading patients to avoid seeking follow-up observation, the groups wrote at the time, concluding that nalmefene shouldn’t yet replace naloxone as the standard of care for opioid overdose reversal.
Though the RESPIRE experts acknowledged the increased risk of precipitated withdrawal following overdose reversal with nalmefene, they wrote that such risks are “secondary to saving a life.”
“With the ability to medically manage precipitated withdrawal, in concert with the uncertainty and unpredictability of HPSOs, overdose reversal strategies and agents that rapidly restore and sustain respiration should be aggressively implemented,” they wrote.
The panel concluded by calling for greater research and real-world evidence collection around treatments for HPSO overdoses. And, to boost treatment with both naloxone and nalmefene, they “emphatically” recommended improvements to bystander education and training, greater access to reversal agents and a wide-scale destigmatization of addiction.
“Only with investments in using new reversal medications, further controlled trials yielding strong evidence, adequately training bystanders and first responders, collecting outcome information, researching and developing new reversal agents, and improving access to opioid use disorder treatment and prevention will the opioid overdose epidemic be marshaled to avoid needless deaths,” they wrote.