S3035 Drug-Induced Intestinal Necrosis: Disproportionality Analysis Using the FDA Adverse Event Reporting System (FAERS) Database

Introduction: Drug-induced intestinal necrosis is a severe and potentially life-threatening condition characterized by the death of the intestinal tissue. Typical symptoms include abdominal pain, vomiting, diarrhea, and fever. This can rapidly progress to severe complications such as septic shock and peritonitis. Early recognition and prompt discontinuation of the offending drug are crucial to mitigate the risk of severe complications and improve patient outcomes. This is a real-world pharmacovigilance study evaluating the association between various drugs and intestinal necrosis. Methods: The Food and Drug Administration (FDA) maintains the Adverse Event Reporting System (FAERS) database. As of December 31, 2024, the database contained 30,179,725 reported events. This database was queried to identify all reported cases of ‘Gastrointestinal necrosis’, ‘Gastrointestinal mucosal necrosis’, ‘intestinal gangrene’, and ‘gastrointestinal gangrene’. All medications implicated were identified by their generic names. The database does not report how the diagnosis of necrosis was confirmed, nor whether other causes were ruled out. A disproportionality analysis was conducted, wherein Reporting Odds Ratios (ROR) were calculated. An ROR >1 is considered a significant signal. Results: A total of 3752 cases were reported to the FAERS from 1970-2024. 3701 were characterized as severe, including 1589 deaths (42.35%). The most common reported drugs were – Docetaxel (3.86%; ROR: 13.9 [11.77, 16.41]; P < 0.05), Adalimumab (3.46%; ROR: 1.45 [1.22, 1.73]; P < 0.05), Fluorouracil (3.38%; ROR: 13.89 [11.64, 16.58]; P < 0.05), Clozapine (3.22%; ROR: 6.99 [5.83, 8.38]; P < 0.05), Cyclophosphamide (3.14%; ROR: 6.94 [5.83, 8.26]; P < 0.05), Methotrexate (3.11%; ROR: 5.00 [4.16, 6.01]; P < 0.05), Paclitaxel (3.04%; ROR: 9.09 [7.54, 10.95]; P < 0.05), Bevacizumab (2.77%; ROR: 7.95 [6.54, 9.66]; P < 0.05), Cytarabine (2.77%; ROR: 15.43 [12.70, 18.76]; P < 0.05), and Cisplatin (2.48%; ROR: 10.84 [8.82, 13.32]; P < 0.05). Conclusion: Docetaxel was the most reported cause of drug-induced intestinal necrosis (3.6% of all reports), while Cytarabine had the highest ROR (15.43) amongst the most frequently reported drugs. A high degree of suspicion should be employed when patients present with warning symptoms after a recent change in medications. Such patients should discontinue these medications when possible, and immediate supportive care should be instituted.