Exploring the Promising Role of Intranasal Epinephrine in Anaphylaxis: A Narrative Review

Anaphylaxis is a rapid-onset, severe allergic reaction that can be life-threatening and requires prompt treatment. Intramuscular (IM) epinephrine remains the standard first-line treatment; however, delayed or incorrect use of injectable devices, needle fear, and access barriers can limit timely administration. In this narrative review, we examine the potential role of intranasal epinephrine (INE) as a non-invasive alternative, particularly when IM administration is difficult. Peer-reviewed literature published from January 2010 through August 2026 was searched in PubMed, Scopus, Web of Science, and Google Scholar, with additional regulatory sources and reference-list screening. Evidence relating to pharmacokinetics, pharmacodynamics, safety, tolerability, formulation, and regulatory status was included. Studies generally demonstrate systemic absorption of INE and, for newer formulations, pharmacokinetic and pharmacodynamic profiles comparable with IM epinephrine or autoinjectors. Neffy (epinephrine nasal spray) received Food and Drug Administration approval in 2024 for emergency treatment of Type I allergic reactions, including anaphylaxis, in adults and pediatric patients weighing at least 30 kg. INE offers a needle-free and potentially more accessible option, but variability in absorption, nasal conditions, dose selection, and the limited availability of clinical outcome data remain important considerations. Further studies are required to establish its long-term safety, optimal dosing, and role across different patient populations.