Beyond the Auto‑Injector: Emerging Epinephrine Delivery Options and Practical Takeaways

Epinephrine auto‑injectors remain the standard outpatient delivery system for anaphylaxis, but their limitations contribute to underuse in real‑world settings. Barriers include needle phobia, device bulk, inconsistent carriage, and concerns about correct administration technique. Furthermore, fixed‑dose devices (0.1 mg, 0.15 mg, and 0.3 mg in the United States) may underdose larger adults because 0.3 mg corresponds roughly to a 0.01 mg/kg dose for a 30‑kg (approximately 66‑lb) patient. Although drawn‑up intramuscular epinephrine from a syringe and vial remains an option in health care settings, it is less practical for lay caregivers and associated with slower absorption compared with auto‑injectors.

These challenges have spurred development of novel epinephrine formulations aimed at improving usability, portability, and stability. Intranasal epinephrine spray is now commercially available and was approved via a pharmacokinetic pathway demonstrating plasma exposure within the range of existing intramuscular products. Early experience suggests that a needle‑free option may improve willingness to carry and use epinephrine promptly, particularly among individuals with significant needle aversion. Other investigational approaches include sublingual film technologies that deliver epinephrine prodrugs for rapid absorption, as well as additional intranasal and inhaled candidates. Advantages of these newer platforms may include improved temperature tolerance, reduced concern about storage in hot or cold environments, and extended shelf life compared with traditional auto‑injectors.

In the final segment of the video, Schroer, Golden, and Lieberman explore how these alternative delivery systems may reshape anaphylaxis care. They note that for some patients—especially young children at risk for injection‑related injury or adults with obesity in whom auto‑injector needle length may not reliably reach muscle—intranasal epinephrine could offer pharmacologic and practical advantages. Lieberman highlights a sublingual prodrug film in late‑stage development and emphasizes that patients frequently prefer oral or needle‑free options when given a choice. The experts also underscore pragmatic benefits such as longer expiration intervals, which may reduce the economic burden associated with frequent device replacement, and they conclude by reiterating core themes from the updated guidelines: epinephrine should be used early and without unnecessary barriers, corticosteroids should not be routine in acute anaphylaxis, and structured anaphylaxis emergency action plans should be provided to at‑risk patients at the point of care.

Disclosures include Novartis Pharmaceuticals, Regeneron Pharmaceuticals, BioCryst, GlaxoSmithKline, Amgen, GENZYME Corporation, AstraZeneca Pharmaceuticals, and LEO Pharma for Schroer; Novartis Pharmaceuticals, ABBVIE, Genentech, Aquestive Therapeutics for Lieberman; and Phadia US and Genentech USA for Golden.

References:

1. Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124-176. doi:10.1016/j.anai.2023.09.015

2. ARS Pharma. ARS Pharmaceuticals Announces FDA Approval of neffy® 1 mg (epinephrine nasal spray) for Type I Allergic Reactions, Including Anaphylaxis, in Pediatric Patients Weighing 15 to < 30 Kilograms - ARS Pharmaceuticals. ARS Pharmaceuticals. Published March 5, 2025. Accessed February 20, 2026. https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-announces-fda-approval-neffyr-1-mg

3. Aquestive Therapeutics. Aquestive Therapeutics Announces FDA Issuance of Complete Response Letter for Anaphylm^TM - Aquestive Therapeutics. Aquestive Therapeutics. Published February 6, 2026. Accessed February 20, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-issuance-complete-response