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Despite its therapeutic utility, flecainide has a narrow safety margin and potential for fatal toxicity. This study presents a forensic case of fatal flecainide intoxication and investigates the role of pharmacogenetics in drug metabolism and toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 27-year-old medical doctor, prescribed flecainide, was found deceased. Postmortem examination included histological and toxicological analyses of blood and urine samples, with flecainide quantification by a validated method. CYP2D6 and CYP3A5 were genotyped to check for variants of the respective drug-metabolizing enzymes. A literature review of fatal and non-fatal flecainide intoxication is also presented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Flecainide concentrations measured 3.411 mg\/l and 2.962 mg\/l in central and peripheral blood, respectively. Pharmacogenetic analysis identified a CYP3A5 *3\/*3 poor metabolizer genotype, likely contributing to reduced drug clearance and increased toxicity. Histology revealed mild coronary stenosis and signs consistent with cardiogenic shock. The death was deemed a suicide, possibly facilitated by abnormal metabolic phenotype in a mildly compromised cardiac substrate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case highlights the complexities in diagnosing lethal flecainide intoxication, particularly considering postmortem concentration variability and individual metabolic differences. Integrating pharmacogenetic data enhances interpretation of toxicological findings and may guide personalized therapeutic strategies to mitigate risk. Further research is warranted to clarify genetic influences on flecainide toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12024-026-01188-8","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T08:19:39Z","timestamp":1772871579000},"page":"944-956","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Suicide by flecainide: a case report and review of the literature"],"prefix":"10.1007","volume":"22","author":[{"given":"Angelo","family":"Montana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio Lo","family":"Faro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Turchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Alessandrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0441-9787","authenticated-orcid":false,"given":"Arianna","family":"Giorgetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"1188_CR1","unstructured":"Arunachalam K, Alzahrani T. 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According to Italian legislation, Ethical Approval for a single case is not required, as long as the data are kept anonymous and no identifying genetic results are involved.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current Italian legislation neither requires the family\u2019s consent or ethical approval for a single case, as long as the data are kept strictly anonymous. Because summoning the parents was not possible as it would badly interfere with the grieving process, parents\u2019 consent was completely waived, according to the Italian Authority of Privacy and Data Protection (\u201cGarante della Privacy\u201d: GDPR nr 679\/2016; 9\/2016 and recent law addition number 424\/ 19th of July 2018;\n                      \n                      ).","order":2,"name":"Ethics","label":"Informed Consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}