Signal detection of drug-induced esophageal ulcer across 20 years of real-world study: Focus on 49 high-risk medicines

ObjectiveTo systematically identify drug-induced esophageal ulcer and address existing knowledge gaps.MethodsWe conducted a real-world study using the Food and Drug Administration Adverse Event Reporting System database from Q1 2004 to Q4 2024. Disproportionality analyses were performed to evaluate drug-induced esophageal ulcer risk. Data for each drug were merged and screened using the RxNax platform to recalculate drug exposure, proportional reporting ratio, reporting odds ratio, and chi-squared values. High-risk drugs classified by anatomical therapeutic chemical classification system were cross-checked with Side Effect Resource, product labels, and published literature.ResultsA total of 12,763 drug-induced esophageal ulcer cases were identified. Forty-nine high-risk drugs, spanning nine anatomical therapeutic chemical classification system classes, were detected, including antineoplastics and immunomodulators (Class L), systemic anti-infectives (Class J), and drugs affecting the musculoskeletal system (Class M). Aspirin, alendronic acid, and doxycycline were most frequently reported; doxycycline, clindamycin, and alendronic acid generated the strongest safety signals. Antineoplastics/immunomodulators (anatomical therapeutic chemical classification system L) had the highest cumulative proportional reporting ratio, primarily driven by tacrolimus, mycophenolic acid, and sunitinib. Notably, tacrolimus, sunitinib, meclofenamic acid, clopidogrel, and erlotinib were associated with esophageal ulcers but remain unlabeled for this risk.ConclusionsThis study provides a comprehensive drug-induced esophageal ulcer risk profile, highlighting high-risk drugs beyond commonly recognized agents. These findings can inform safer prescribing practices, patient counseling, and targeted pharmacovigilance.