Nalmefene: Concerns About New Overdose Antidote Explained
The first nalmefene hydrochloride (HCl) auto-injector (Zurnai) brings a fresh tool to the fight in opposition to the opioid overdose epidemic nonetheless will not be without controversy.
As reported earlier this month, the US Food and Drug Administration (FDA) licensed Purdue Pharma’s abbreviated fresh drug utility for a prefilled, single 1.5-mg dose of nalmefene auto-injector for the emergency treatment of opioid overdose in of us historical 12 years or older.
Nalmefene HCl injection modified into first licensed in 1995 (Revex) nonetheless discontinued for industrial causes in 2008 by Baxter Healthcare. The FDA granted approval of nalmefene injection to Purdue in 2022 and licensed the first nalmefene nasal spray (Opvee), sold by drugmaker Indivior, in 2023.
Consultants are renewing considerations about the shortage of clinical trial files on nalmefene within the latest generation of extremely potent synthetic opioids fancy fentanyl and the aptitude for severe, extended withdrawal. For some, there might perhaps be additionally the sting of searching for an opioid reversal agent from the OxyContin maker and its billionaire house owners, the Sackler family.
How Does it Work?
Nalmefene is an opioid antagonist structurally same to naltrexone and has bigger affinity for opioid receptors than naloxone, the most consuming various opioid antidote obtainable within the United States.
Nalmefene has a half of-existence averaging 10.8 hours after a 1-mg intravenous dose when put next with 30-90 minutes for naloxone reckoning on the route of administration.
While expanding treatment suggestions for opioid overdose is crucial for public health, Smita Das, MD, PhD, MPH, clinical accomplice professor of psychiatry and behavioral sciences at Stanford College College of Remedy, Stanford, California, instructed Medscape Medical Data that nalmefene’s longer half of-existence might perhaps perhaps end result in more severe precipitated opioid withdrawal.
Zurnai’s mark carries a warning for precipitation of severe opioid withdrawal in patients who’re opioid dependent characterized by symptoms that encompass physique aches, fever, and vomiting nonetheless additionally tachycardia, restlessness, and elevated blood tension.
“Withdrawal with nalmefene might perhaps perhaps additionally honest be so severe that a person might perhaps perhaps additionally honest be averse to the utilization of the agent or, worse yet, strive and overcome the withdrawal by the utilization of even more opioids,” Das acknowledged.
Extra, nalmefene’s longer half of-existence might perhaps perhaps additionally honest give the user a counterfeit sense that they’ve more time to glance emergency attention. In addition, patients might perhaps perhaps additionally honest require longer commentary occasions within the emergency environment, she mighty.
Clinicians are unable to search out out a loyal commentary duration after nalmefene dissipates because this protracted duration will not be favorable for the patient, acknowledged Jeanmarie Perrone, MD, professor of emergency treatment and director of Heart for Dependancy Remedy and Protection, College of Pennsylvania, Philadelphia.
“Patients in withdrawal aren’t in a arena to dangle discussions about treatment suggestions and might perhaps perhaps additionally honest likely must movement away the emergency department without warning to self-tackle their withdrawal,” she instructed Medscape Medical Data. “However, the length of self-treatment and titrating their symptom management and reversal of nalmefene is complicated and might perhaps perhaps additionally honest end result in repeat overdose within the next 6-24 hours,” she added.
Each Perrone and Das win more study is obligatory into nalmefene’s security and efficacy, namely in extremely potent synthetic opioid overdoses. As beforehand reported by Medscape Medical Data, the American College of Medical Toxicology (ACMT) and the American Academy of Clinical Toxicology (AACT) made the an identical inquire after the nalmefene nasal spray modified into licensed and called out its likely to trigger bother by extended withdrawal.
“A nalmefene auto-injector would additionally be longer-performing than naloxone, so I even dangle the an identical considerations,” Medical Toxicologist Andrew Stolbach, MD, coauthor of the ACMT/AACT location tell and accomplice professor of emergency treatment, Johns Hopkins College College of Remedy in Baltimore, acknowledged in an interview.
Stolbach believes naloxone might perhaps perhaps additionally honest mute remain the first-line reversal agent nonetheless that he can fancy why, within the course of a unpleasant opioid epidemic, the FDA allowed Purdue to utilize the abbreviated approval job for nalmefene. “I’m in my draw k with it being on the market, I honest win not survey what the clinical role for it’s,” he acknowledged.
That acknowledged, Stolbach has a matter with Purdue commercials spinning the bigger affinity and longer length of nalmefene as a income.
“We already survey diverse naloxone where patients win a broad dose prehospital and so they’re in withdrawal, nonetheless it would not ultimate too lengthy. It is likely you’ll additionally measure it in minutes,” he mighty. “What’s going to happen now when of us were sold this nalmefene, and we’ve obtained patients coming in with an extended duration of withdrawal?”
“When I survey ambulances being stocked with this fresh drug that could be costlier — nonetheless or not it’s absolutely not any better than the veteran drug — and I win marketing emails now for nalmefene, it honest seems fancy property being set to resolve a matter we didn’t dangle,” Stolbach added.
A spokesperson for Purdue instructed Medscape Medical Data in an e-mail that stories evaluating naloxone with nalmefene specific to the depth of withdrawal haven’t been performed. “Extra, an extended size of cease and elevated resource utilization is speculative in step with the longer length of action of nalmefene when put next with naloxone, nonetheless these outcomes haven’t been evaluated,” the spokesperson mighty.
Safety and Efficacy: What to Know
Zurnai is indicated for intramuscular and subcutaneous use most consuming and might perhaps perhaps additionally honest also be readministered with a fresh auto-injector every 2-5 minutes if the patient would not answer or relapses into respiratory despair, the drug mark mighty.
Harmful reactions occurred in 63.6% of 44 wholesome adults after one 1.5-mg intramuscular dose of Zurnai, in step with pooled files from a pharmacokinetic leer and a pharmacodynamic leer cited within the mark. Among the crucial detrimental events occurring in more than 5% of volunteers included palpitations (9.1%), nausea (18.2%), vomiting (11.4%), allodynia (11.4%), feeling sizzling (25.0%), chills (13.6%), dizziness (15.9%), and headache (18.2%).
The mark additionally carries warnings about recurrent respiratory despair, even after an it seems ample preliminary response, and the threat for restricted efficacy with partial agonists or mixed agonist/antagonists honest like buprenorphine and pentazocine.
“I win not win that the nalmefene auto-injector provides the leisure to the dependancy armamentarium,” acknowledged Kelly S. Ramsey, MD, MPH, an dependancy treatment and bother reduction consultant in internal most follow in Olivebridge, Contemporary York, and a regional director, American Society of Dependancy Remedy.
She highlighted a double-blind, randomized leer in 176 patients whereby intravenous 1- and 2-mg nalmefene and 1-mg naloxone yielded same clinical outcomes, nonetheless patients receiving nalmefene had twice as many detrimental effects as these who obtained naloxone.
“Notably, there’ll not be one of these thing as a clinical files to beef up nalmefene’s use since the 1990s, and there modified into no clinical files with nalmefene’s use in opposition to extremely potent synthetic opioids or any arena stories with americans that use treatment (PWUD),” Ramsey acknowledged. “Connected to the approval of high-dose (8-mg) naloxone, which additionally had no arena stories done in PWUD earlier than approval, the voices of PWUD and of bother reductionists are being overlooked.”
“The genuine recount is below recognition of polysubstance overdose and the role that various substances location in overdose,” she added.
Purdue Weighs In
Asked what stories had been primitive to beef up the Zurnai auto-injector, Purdue supplied a hyperlink to the FDA press unlock and acknowledged “the treatment went by the intensive FDA-approval job which requires an remarkable quantity of files. That capabilities security and pharmacokinetic stories, as correctly as a leer in wholesome americans who use opioids recreationally, to assess how quickly the product works.”
In June, the US Supreme Court rejected a financial catastrophe settlement that might perhaps perhaps dangle supplied as a lot as $6 billion to establish proceedings filed in opposition to Purdue in commerce for immunity to the Sackler family from civil claims connected to its role within the opioid disaster.
“While the drug firm might perhaps perhaps additionally honest be publicizing that they are selling the drug (nalmefene) at ticket, it’s hideous that they contributed to the opioid and overdose crises of the 1990s, the outcomes of that are mute being confronted this day by communities,” Das acknowledged. “Understandably, there are conflicted sentiments about a firm making an strive to sell an antidote for the very recount they helped homicide.”
Stolbach acknowledged that there are clinicians that by no system must dangle the leisure to cease with Purdue. “For me in my draw, I honest strive and search on the drug as a tool and separate it from the producer.”
What’s Subsequent?
Zurnai might perhaps be obtainable in 2025 nonetheless “the value is yet to make certain,” Purdue’s spokesperson mighty.
“We are making every effort to lift the value down as small as that it’s likely you’ll additionally factor in to maximise win admission to and availability, and we are working to distribute Zurnai at no income to Purdue as segment of our ongoing Public Health Initiatives,” they added.
Based entirely on Purdue, postmarketing stories are being deliberate, and a prospective, randomized trial is underway in Contemporary Mexico evaluating the efficacy and security of nalmefene HCl injection with these of naloxone injection for recurrent respiratory despair due to opioid overdose within the emergency room.
Das, Perrone, Stolbach, and Ramsey reported no relevant financial relationships.
