{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:08:46Z","timestamp":1785816526752,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background\/Rationale<\/jats:title><jats:p>Benzodiazepine\u2010involved overdose deaths are increasing. Flumazenil is rarely used due to fear of seizures; however, the risk benefit may favour its use. Flumazenil is licensed for intravenous (IV) use, but intramuscular (IM) treatment would be required pre\u2010hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify and synthesise pre\u2010clinical and clinical data on the parenteral IM flumazenil safety and efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PubMed, Google Scholar, Cochrane and Scopus searches without any language restriction. Adverse effect studies were limited to systematic reviews and large cohort studies (<jats:italic>n<\/jats:italic>\u2009&gt;\u2009100), IM administration efficacy to studies in large animal (mammalian, excluding reptiles and birds) and humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two systematic reviews reported adverse effects from IV or IM flumazenil in clinical use and combined retrospective\/prospective patient cohort. Seizures were uncommon (&lt;\u20092%) including mixed overdoses. Seven studies (four animal, three human) reported on IM flumazenil. Animal studies indicated IM flumazenil efficacy. In a canine cross\u2010over study, IM flumazenil reversed midazolam sedation moderately slower than IV. Two clinical observational studies reported sedation reversal with IM flumazenil, whereas a cross\u2010over study found no IM flumazenil response at 15\u2009min.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IM flumazenil data are sparse, but it may be effective and safe. Clinical research is urgently needed to determine whether pre\u2010hospital IM flumazenil can prevent benzodiazepine\u2010involved overdose deaths.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcpt.70007","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T06:14:11Z","timestamp":1739513651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Could Flumazenil Be Used Pre\u2010hospital by Intramuscular Injection for Coma due to Mixed Drug Overdose Not Responding to Naloxone?: A Systematic Review of the Evidence"],"prefix":"10.1111","volume":"136","author":[{"given":"Ilinca","family":"Farcas","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-672X","authenticated-orcid":false,"given":"Lisa","family":"Sch\u00f6lin","sequence":"additional","affiliation":[{"name":"Centre for Pesticide Suicide Prevention, and Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eddleston","sequence":"additional","affiliation":[{"name":"Centre for Pesticide Suicide Prevention, and Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"United Nations Office on Drugs and Crime \u201cWorld Drug Report 2024. 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