By: Rebecca Sabzanov, PharmD Candidate c/o 2026

On August 9^th, 2024, the Food and Drug Administration (FDA) approved Neffy, the first epinephrine intranasal spray, manufactured by ARS pharmaceuticals, for the treatment of anaphylaxis in adults and pediatric patients who weigh at least 30 kilograms.¹ Anaphylaxis is a severe allergic reaction which causes a multitude of symptoms, including skin reactions, respiratory problems, cardiovascular issues, and can therefore      be life-threatening. Epinephrine is the first-line treatment of anaphylaxisand is usually administered via EpiPen, an auto-injector needle that is administered into the thigh.² Unlike traditional epinephrine delivery methods such as the EpiPen, Neffy is the first needle-free option to treat anaphylaxis.

Epinephrine is a sympathomimetic catecholamine that has dose dependent effects on both alpha-adrenergic and beta-adrenergic receptors. Smaller doses of epinephrine have a higher affinity for beta receptors, while higher doses selectively work on alpha receptors. On alpha-1 receptors, epinephrine promotes vasoconstriction, increased heart rate, and bronchodilation. This helps treats anaphylaxis as anaphylaxis leads to widespread vasodilation and airway constriction through the release of histamine and other inflammatory mediators from activated mast cells, which leads to hypotension. When epinephrine activates alpha-1 receptors, it reverses almost all signs of anaphylaxis by stabilizing mast cells, by causing vasoconstriction to counteract the extreme vasodilation that occurs, and by promoting bronchodilation through relaxation of the smooth muscles in the airway.³

In an analysis published by Elsevier, different administration methods of epinephrine were compared, specifically focusing on pharmacokinetic and pharmacodynamic profiles.     These included: maximum plasma concentration (C_max), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR).⁴ Methods of administration of Epinephrine included manual intramuscular 0.3 mg epinephrine injection, autoinjector EpiPen, autoinjector Symjepi, and intranasal spray Neffy. The mean C_max of Neffy (258 pg/mL) was comparable to the mean C_max of Epinephrine 0.3 mg IM (254 pg/mL). EpiPen and Symjepi showed the highest mean C_max values, 503 pg/mL and 438 pg/mL, respectively. For SBP, EpiPen had the highest mean systolic blood pressure maximum effect (18.1 mm Hg), followed by Neffy (16.9 mm Hg), Symjepi (14.9 mm Hg), and Epinephrine 0.3 mg IM (10.9 mm Hg). For diastolic blood pressure, Neffy was the only product of the ones tested which increased the mean DBP. The peak mean heart rate over time was highest for EpiPen, followed by Neffy, then Epinephrine 0.3 mg IM, and lastly Symjepi. The analysis concluded based on the results that Neffy showed comparable or higher pharmacodynamic responses relative to currently available delivery systems for epinephrine, despite having lower end of C_max.⁴

The approval of Neffy is significant as the first non-injectable treatment of anaphylaxis and can address a critical barrier to timely treatment for those who have a fear of needles, commonly seen in both children who receive the medication and parents who need to administer the medication.⁵ Besides its key feature of noninvasive delivery, it offers ease of use, requiring a single spray in one nostril, and portability, as it is small and convenient to carry. This is a substantial advancement in the management of anaphylaxis.

References:

1. Office. FDA Approves First Nasal Spray for Treatment of Anaphylaxis. U.S. Food and Drug Administration. Published 2024. Accessed August 19, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis?utm_source=MarketingCloud&utm_medium=email&utm_campaign=PT+Daily+August+12&utm_content=PT+Daily+August+12
2. Morriello, F., & Chapman, M. (2023). Epinephrine in anaphylaxis. CMAJ: Canadian Medical Association Journal, 195(19), E683–E683. https://doi.org/10.1503/cmaj.221319
3. Brown JC, Simons E, Rudders SA. Epinephrine in the management of anaphylaxis. The Journal of Allergy and Clinical Immunology: In Practice. 2020;8(4):1186-1195. doi:https://doi.org/10.1016/j.jaip.2019.12.015
4. Tanimoto S, Kaliner M, Lockey RF, et al. Pharmacokinetic and Pharmacodynamic Comparison of Epinephrine administered intranasally and intramuscularly: an integrated analysis. Annals of Allergy, Asthma & Immunology. Published online November 2022. doi:https://doi.org/10.1016/j.anai.2022.10.024
5. Narchi, H., Elghoudi, A., & Al Dhaheri, K. (2022). Barriers and challenges affecting parents’ use of adrenaline auto-injector in children with anaphylaxis. World Journal of Clinical Pediatrics, 11(2), 151–159. https://doi.org/10.5409/wjcp.v11.i2.151