Clinical Question: How does Neffy (epinephrine nasal spray) compare to the Epinephrine autoinjectors?
Background:
Neffy (epinephrine) nasal spray and epinephrine IM autoinjectors are both approved for the emergency treatment of type I allergic reactions, including anaphylaxis, for both adult and pediatric patients.
Both deliver routes of epinephrine, an alpha and beta-adrenergic agonist, have similar mechanisms of action.
Answer:
Clinical studies demonstrate that Neffy 2 mg intranasal spray achieves plasma epinephrine concentrations and hemodynamic responses (↑ SBP & DBP) that are comparable to 0.3 mg IM injection via autoinjector.
In the studies it was found that the onset of Neffy is as early as 1–5 minutes after administration. This rapid onset is comparable to IM epinephrine, and in some studies, the initial plasma concentrations with Neffy may be numerically higher than IM injection during the first 5–10 minutes post-dose.
The duration of effect of Neffy nasal spray is similar to IM injection and is approximately 60 minutes.
Neffy dosing is weight based. If patient ≥30Kg, give one 2mg spray into a nostril. If patient 15Kg - 29Kg, give one 1mg spray into a nostril. May repeat x 1 in 5 minutes.
Most frequently reported reactions with Neffy include nasal discomfort, rhinorrhea, nasal congestion, and throat irritation. These effects are generally mild and transient.
Conclusion:
Neffy (epinephrine nasal spray) is a needle-free, easy alternative to epinephrine IM autoinjectors, with comparable pharmacokinetic, pharmacodynamic, and safety profiles.
Having an alternative intranasal delivery route may improve timely administration in patients reluctant to use injectable devices.
References:
Casale TB, Ellis AK, Nowak-Wegrzyn A, et al. Pharmacokinetics/Pharmacodynamics of Epinephrine After Single and Repeat Administration of Neffy, EpiPen, and Manual Intramuscular Injection. The Journal of Allergy and Clinical Immunology. 2023;152(6):1587-1596. doi:10.1016/j.jaci.2023.08.007.
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 : Official Publication of the American College of Allergy, Asthma, & Immunology. 2023;130(4):508-514.e1. doi:10.1016/j.anai.2022.10.024.
Ebisawa M, Takahashi K, Takahashi K, et al. Epinephrine Nasal Spray Improves Allergic Symptoms in Patients Undergoing Oral Food Challenge, Phase 3 Trial. The Journal of Allergy and Clinical Immunology. In Practice. 2025;:S2213-2198(25)00630-0. Doi:10.1016/j.jaip.2025.06.038.
Ellis AK, Casale TB, Kaliner M, et al. Development of Neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions. Pharmaceutics. 2024;16(6):811. doi:10.3390/pharmaceutics16060811.
Pouessel G, Neukirch C. Alternatives to Injectable Adrenaline for Treating Anaphylaxis. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2025;55(1):36-51. doi:10.1111/cea.14598.
Authored by Joanne Routsolias, PharmD