b'PACEP EMS UpdateNalmefene in the Prehospital Setting:Evidence, Safety, and Policy ConsiderationsAvram Flamm, DO, FACEP|Stephanie Costa, MDPennsylvania House Bill 2182 proposes addingopioids. They further conclude that Nalmefene a second opioid antagonistNALMEFENEtoshould not replace Naloxone as the primary the Pennsylvania prehospital formulary alongsideopioid antidote at this time (https://www.acmt.NALOXONE. We share significant concerns relatednet/wp-content/uploads/2023/12/ACMT-AACT-to the safety of this proposal. Joint-PS_Nalmefene.pdf).As overdose deaths continue to strain EMSThe principal adverse effect of any opioid systems and emergency departments across theantagonist remains precipitated withdrawal, Commonwealth, any proposed enhancementparticularly in opioid-dependent individuals. to overdose response deserves thoughtfulWithdrawal may manifest as severe agitation, consideration. However, formulary expansion mustpersistent vomiting, hypertension, dysrhythmias, remain grounded in pharmacology, evidence,respiratory complications, and marked operational feasibility, and above all, patient safety.sympathetic activation. In rare cases, stress-There is universal agreement on the objective:induced cardiomyopathy or acute respiratory rapid reversal of life-threatening opioid toxicitydistress syndrome has been reported. With saves lives. NALOXONE has a more than 50-yearNaloxone, these symptoms are typically time-safety and efficacy record. It acts quickly, reliablylimited, often improving within 6090 minutes as restores ventilation, and is deeply embeddedthe medications effects diminish.in EMS, emergency medicine, hospital, and lawIn contrast, Nalmefene has a markedly longer enforcement practice. It is cost effective, widelyelimination half-lifepotentially exceeding 10 distributed, and extensively studied. Importantly,hours. Prolonged receptor antagonism may extend contemporary toxicology literature confirmsboth the duration and severity of withdrawal. that appropriately titrated doses of NaloxoneThe ACMT/AACT statement cautions that use of a effectively reverse fentanyl-related overdoseslonger-acting antagonist could potentially cause without requiring a higher-affinity antagonist.harm, particularly through extended precipitated NALMEFENE, a opioid antagonist recently alsowithdrawal and increased resource utilization. available in intranasal form, is marketed primarilyWhen withdrawal is prolonged, treatment options for its prolonged duration of action. On initialare limited; supportive care and sedation are often review, a longer-acting reversal agent may appearthe only available strategies until the antagonist advantageous. However, its pharmacologic profileeffect dissipates.raises clinically significant concerns in the EMS andIn operational terms, longer-lasting withdrawal ED environments. has downstream consequences: increased The American College of Medical Toxicologysedation requirements, heightened scene (ACMT) and the American Academy of Clinicalsafety concerns, prolonged ED observation, and Toxicology (AACT) emphasize in their jointextended hospital stays. In already resource-position statement that the current standardconstrained systems, these effects are not trivial.opioid antidote, Naloxone, has a sufficiently highEqually important is the evidentiary foundation. opioid receptor affinity to reverse novel syntheticNalmefene received FDA approval for intranasal 26 PACEP News'