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Uridine triacetate is as an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year, with 20\u201030% developing severe or life\u2010threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic prescreening is recommended prior to starting fluoropyrimidine agents, this only prevents 20\u201030% of early\u2010onset life\u2010threatening toxicity and so does not obviate the need for an antidote. Initial in\u2010human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5\u2010FU bolus dose. A lack of clinical equipoise meant a placebo\u2010controlled phase III trial was not ethical and so the phase III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30\u2009days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120\u2010504\u2009h after last fluoropyrimidine administration, suggesting efficacy beyond the FDA licencing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of tegafur (a 5\u2010FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis.<\/jats:p>","DOI":"10.1111\/bcp.16319","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T06:32:08Z","timestamp":1730183528000},"page":"615-627","source":"Crossref","is-referenced-by-count":8,"title":["Review of the fluoropyrimidine antidote uridine triacetate"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6480-3779","authenticated-orcid":false,"given":"Jack T.","family":"Thompson","sequence":"first","affiliation":[{"name":"Clinical Toxicology Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-7237","authenticated-orcid":false,"given":"David M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Guy's and St Thomas' NHS Foundation Trust  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3433-9622","authenticated-orcid":false,"given":"Paul I.","family":"Dargan","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Guy's and St Thomas' NHS Foundation Trust  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30321"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.28.15_suppl.9084"},{"key":"e_1_2_10_4_1","volume-title":"Clinical experience with uridine triacetate for 5\u2010fluorouracil overexposure: an update. 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