{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:30:34Z","timestamp":1788985834612,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARS Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity\/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy\u2019s development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of \u03b1 and \u03b2 adrenergic receptors, which are the key components of epinephrine\u2019s mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.<\/jats:p>","DOI":"10.3390\/pharmaceutics16060811","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:52:10Z","timestamp":1718355130000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions"],"prefix":"10.3390","volume":"16","author":[{"given":"Anne K.","family":"Ellis","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Medicine, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Casale","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kaliner","sequence":"additional","affiliation":[{"name":"Institute for Asthma and Allergy, Chevy Chase, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3260-9630","authenticated-orcid":false,"given":"John","family":"Oppenheimer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Spergel","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Fleischer","sequence":"additional","affiliation":[{"name":"Section of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital Colorado, School of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Bernstein Clinical Research Center, Division of Immunology, Allergy and Rheumatology, College of Medicine, University of Cincinnati, Cincinnati, OH 45236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5071-7654","authenticated-orcid":false,"suffix":"Jr.","given":"Carlos A.","family":"Camargo","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lowenthal","sequence":"additional","affiliation":[{"name":"ARS Pharmaceuticals, Inc., San Diego, CA 92130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"ARS Pharmaceuticals, Inc., San Diego, CA 92130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.annemergmed.2017.02.015","article-title":"When to pick the nose: Out-of-hospital and emergency department intranasal administration of medications","volume":"70","author":"Rech","year":"2017","journal-title":"Ann. 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