Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto-Injector Versus Intranasal Naloxone.

ABSTRACT: As illegally made fentanyl and congeners continue to drive overdose deaths in the US, experts have called for stronger and longer-lasting antagonists. A randomized, 4-period, 2-treatment crossover replicate-design study in healthy moderately-experienced opioid users (n = 24) evaluated the reversal of opioid-induced respiratory depression (OIRD) by intramuscular (IM) nalmefene 1.5 mg administered by auto-injector delivering a formulation developed for faster onset, compared to intranasal (IN) naloxone 4 mg. Fentanyl infusions were administered to induce a 50% reduction in minute ventilation (MV). Reversal of OIRD, pharmacokinetics, and safety were investigated under steady-state fentanyl agonism. For the primary endpoint, nalmefene demonstrated superiority at 5 min with an MV increase of 4.

SUBMITTER: Cipriano A 

PROVIDER: S-EPMC12649286 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature