State Rep. Chris Pielli, D-Chester, has introduced a two-bill package designed to allow over-the-counter access to nalmefene, an opioid antagonist approved by the FDA in 2023 but not yet authorized under Pennsylvania's current standing order. The legislation targets a critical gap: while naloxone remains the only approved reversal agent in the state, fentanyl was present in nearly 77% of Pennsylvania's 4,719 overdose deaths in 2023. Pielli argues that first responders and families need more than one option. "We cannot continue to discount the ability of other opioid antagonists to save lives," Pielli said. "Naloxone is a crucial tool for first responders and law enforcement, but it should not be our only option."
The package addresses the issue from both the legislative and regulatory sides. H.B. 2181amends the Controlled Substance Drug, Device, and Cosmetic Act to classify nalmefene as an approved opioid antagonist for over-the-counter use. H.B. 2182directs the Pennsylvania Department of Health to update its standing order to include nalmefene as an approved reversal agent available without a prescription. Together, the bills would allow Pennsylvanians to obtain nalmefene the same way they currently access naloxone: by walking into a participating pharmacy and requesting it.
Nalmefene is not a new drug. Originally FDA-approved for injection in 1995, it was reintroduced as a nasal spray (Opvee) in May 2023. What distinguishes it from naloxone is its pharmacological profile: nalmefene has approximately five times higher binding affinity for opioid receptors and a half-life of 11.4 hours, compared to naloxone's 30 to 90 minutes. This matters because potent synthetic opioids like fentanyl can outlast naloxone's effects, creating the risk of "re-overdose" — when respiratory depression returns after the reversal agent wears off. "While our policy continues to stagnate, the illicit drug market evolves, adapts and finds new ways to draw Pennsylvanians into the throes of addiction or, in an unfortunate number of cases, death," Pielli said.
Nalmefene's reintroduction has not been without controversy. The American College of Medical Toxicology and the American Academy of Clinical Toxicology issued a joint position statement cautioning that nalmefene should not replace naloxone as the primary antidote, citing limited clinical data in real-world overdose settings and the risk that its longer duration could cause more severe withdrawal symptoms. However, translational modeling research has shown nalmefene produced meaningful reductions in cardiac arrest events compared to naloxone following synthetic opioid overdose. Notably, Pielli's bills do not propose replacing naloxone — they propose adding nalmefene as an additional option, expanding the toolkit rather than swapping one tool for another.
The urgency behind this legislation is grounded in data. According to the Pennsylvania Department of Health, approximately one Pennsylvanian died from a drug overdose every two hours in 2023, with 83% of those deaths opioid-related. While recent CDC data shows a decline in overdose deaths from mid-2023 tomid-2024, synthetic opioids remain the dominant driver. Pennsylvania's overdose death rate of 43.2 per 100,000 residents continues to exceed the national average of 32.4 per 100,000, and the state's current naloxone-only framework reflects a policy landscape that has not kept pace with the evolving threat.
Both bills will move through the legislative process in the current session. If passed, Pennsylvania would join a growing number of states reconsidering the scope of their overdose reversal frameworks in response to the synthetic opioid crisis. The practical impact would be felt at the pharmacy counter and in the hands of first responders: another FDA-approved tool available when seconds matter and one dose of naloxone may not be enough.