{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:45:29Z","timestamp":1785822329033,"version":"3.56.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100024158","name":"ARS Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024158","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Allergy Asthma Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Unintentional ocular exposure to epinephrine nasal spray (10\u00a0mg\/mL epinephrine) is a potential safety concern. Although epinephrine is used in multiple ocular formulations, unintentional ocular administration of epinephrine nasal spray was assessed to determine tolerability and support the overall safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A non-GLP ocular tolerability study was conducted using six na\u00efve New Zealand White rabbits (3 males, 3 females). Vehicle control or epinephrine nasal spray (1\u00a0mg) was applied to the right or left eye, respectively, once on Day 1. Animals were monitored over seven days for mortality, clinical signs, body weight changes, ophthalmic findings, ocular irritation (using the Modified Hackett-McDonald Scoring System), and gross necropsy findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Epinephrine nasal spray was well tolerated with no mortality, clinical abnormalities, or changes in body weight. Ophthalmic examinations via indirect ophthalmoscopy and slit-lamp biomicroscopy revealed no signs of irritation or ocular toxicity. No gross pathological changes were noted at necropsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A single topical administration of epinephrine nasal spray (10\u00a0mg\/mL) in rabbit eyes was not associated with any adverse effects, indicating a low risk of ocular toxicity. These results support the safety of epinephrine nasal spray in the event of unintentional ocular exposure and taken together with epinephrine\u2019s use in other ocular formulations, suggest that no further nonclinical ocular studies are necessary.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13223-026-01040-2","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:19:36Z","timestamp":1778127576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low risk of ocular toxicity following topical ocular administration of epinephrine nasal spray: implications for unintentional exposure"],"prefix":"10.1186","volume":"22","author":[{"given":"Anne K.","family":"Ellis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Fleischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Carlos A.","family":"Camargo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lowenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Tanimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"1040_CR1","unstructured":"Neffy Epinephrine Nasal Spray USP. Prescription Information. ARS Pharmaceuticals Operations, Inc; 2025. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/214697s003lbl.pdf. Accessed on 10 November 2025."},{"issue":"1","key":"1040_CR2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1089\/108076802317233216","volume":"18","author":"YL Wang","year":"2002","unstructured":"Wang YL, Hayashi M, Yablonski ME, Toris CB. Effects of multiple dosing of epinephrine on aqueous humor dynamics in human eyes. J Ocul Pharmacol Ther. 2002;18(1):53\u201363.","journal-title":"J Ocul Pharmacol Ther"},{"key":"1040_CR3","doi-asserted-by":"publisher","first-page":"4917659","DOI":"10.1155\/2016\/4917659","volume":"2016","author":"AY Yu","year":"2016","unstructured":"Yu AY, Guo H, Wang QM, Bao FJ, Huang JH. Pupil dilation with intracameral epinephrine hydrochloride during phacoemulsification and intraocular lens implantation. J Ophthalmol. 2016;2016:4917659.","journal-title":"J Ophthalmol"},{"issue":"5","key":"1040_CR4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1111\/aos.13616","volume":"06","author":"J Hult","year":"2018","unstructured":"Hult J, Sheikh R, Nguyen CD, Tenland K, Dahlstrand U, Malmsj\u00f6 M. A waiting time of 7 minutes is sufficient to reduce bleeding in oculoplastic surgery following the administration of epinephrine together with local anaesthesia. Acta Ophthalmol. 2018;06(5):499\u2013502.","journal-title":"Acta Ophthalmol"},{"issue":"811","key":"1040_CR5","first-page":"1","volume":"16","author":"AK Ellis","year":"2024","unstructured":"Ellis AK, Casale TB, Kaliner M, Oppenheimer J, Spergel JM, Fleischer DM, et al. Development of neffy, an epinephrine nasal spray, for severe allergic reactions. Pharmaceutics. 2024;16(811):1\u201316.","journal-title":"Pharmaceutics"},{"key":"1040_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2025.06.038","author":"M Ebisawa","year":"2025","unstructured":"Ebisawa M, Takahashi K, Takahashi KK, Yanagida N, Sato S, Lieberman J, et al. Epinephrine nasal spray improves allergic symptoms in patients undergoing oral food challenge, phase 3 trial. J Allergy Clin Immunol. 2025. https:\/\/doi.org\/10.1016\/j.jaip.2025.06.038.","journal-title":"J Allergy Clin Immunol"},{"key":"1040_CR7","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.jaip.2023.11.006","volume":"12","author":"TB Casale","year":"2023","unstructured":"Casale TB, Oppenheimer J, Kaliner M, Lieberman JA, Lowenthal R, Tanimoto S. Adult pharmacokinetics of self-administration of epinephrine nasal spray 2.0 mg versus manual intramuscular epinephrine 0.3 mg by health care providers. J Allergy Clin Immunol Pract. 2023;12:500-502E1.","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"6","key":"1040_CR8","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.jaip.2025.03.019","volume":"13","author":"DM Fleischer","year":"2025","unstructured":"Fleischer DM, Li HH, Talreja N, Lockey RF, Kaliner MA, Wainford RD, et al. Pharmacokinetics and pharmacodynamics of Neffy, epinephrine nasal spray, in pediatric allergy patients. J Allergy Clin Immunol Pract. 2025;13(6):1335-1341.e1.","journal-title":"J Allergy Clin Immunol Pract"},{"key":"1040_CR9","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1016\/j.jaip.2024.02.038","volume":"12","author":"J Oppenheimer","year":"2024","unstructured":"Oppenheimer J, Casale TB, Camargo CA, Fleischer DM, Bernstein D, Lowenthal R, et al. Upper respiratory tract infections have minimal impact on Neffy\u2019s pharmacokinetics or pharmacodynamics. J Allergy Clin Immunol Pract. 2024;12:1640-1643.e2.","journal-title":"J Allergy Clin Immunol Pract"}],"container-title":["Allergy, Asthma &amp; Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13223-026-01040-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13223-026-01040-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13223-026-01040-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:19:41Z","timestamp":1778127581000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13223-026-01040-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1040"],"URL":"https:\/\/doi.org\/10.1186\/s13223-026-01040-2","relation":{},"ISSN":["1710-1492"],"issn-type":[{"value":"1710-1492","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"assertion":[{"value":"10 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"AK Ellis reports advisory boards for ALK-Abello, AstraZeneca, Bausch Health, Biocryst, Celltrion, Lilly, Novartis, Sanofi and Regeneron; speakers\u2019 bureaus for ALK-Abello, AstraZeneca, Bausch Health, Biocryst, Celltrion, GSK, Medexus, Novartis, Sanofi and Regeneron; research support (paid to institution) from ALK-Abello, AstraZeneca, Bayer LLC, Medexus, Novartis, Sanofi and Regeneron; independent consultant to Bayer LLC and Regeneron; and royalties from UpToDate. She reports serving as a consultant and\/or advisor for ARS Pharmaceuticals. DM Fleischer reports grants from ARS Pharmaceuticals and grants and consultant fees from DBV Technologies and serving as consultant\/advisor for ARS Pharmaceuticals, Aquestive Therapeutics and for Bryn Pharma. CA Camargo, Jr. reports serving as consultant\/advisor for ALK-Abello, ARS Pharmaceuticals, Bryn Pharma, and Aquestive Therapeutics. R Lowenthal and S Tanimoto are employed by ARS Pharmaceuticals Operations, San Diego, CA, USA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}