Pharmacovigilance Analysis of Drug-Induced Stomatitis: Insights From Twenty-One Years of Real-World Data

BACKGROUND: Stomatitis is a common oral disease that seriously affects patients' quality of life. However, the risk of drug-induced stomatitis has not been systematically evaluated based on large-scale real-world data. OBJECTIVES: To identify and validate high-risk drugs associated with drug-induced stomatitis, characterize the baseline features and time-to-onset heterogeneity of drug-induced stomatitis, preliminarily explore underlying mechanisms and provide evidence for clinical risk management. METHODS: This pharmacovigilance study used the FDA Adverse Event Reporting System (FAERS, 2004 Q1-2025 Q3). Disproportionality analysis (ROR, PRR, IC, EBGM), multivariable logistic regression, and time-to-onset (TTO) analysis were applied to identify high-risk drugs. RESULTS: A total of 55,735 stomatitis reports were screened from 58,209,958 records. The majority were female (62.1%), aged 40-80 years, from the United States (55.5%), and reported by health professionals (58.3%). We identified 366 suspicious drugs and confirmed 222 high-risk drugs. The strongest signals were found in antineoplastic and immunomodulatory agents, followed by alimentary tract, nervous system, and anti-infective drugs. TTO analysis showed obvious heterogeneity in onset time among different drug categories. CONCLUSION: This study first systematically identifies high-risk drugs associated with drug-induced stomatitis. The main mechanisms involve mucosal epithelial injury, barrier repair disorder, local irritation, and immune imbalance. These results provide evidence for clinical risk management, rational drug use, and early intervention.