Abstract
INTRODUCTION AND AIMS: Sodium fluoride is widely used in preventive dentistry, yet its global safety profile has not been comprehensively characterised using real-world data. This study aimed to characterise reporting patterns and safety signals associated with sodium fluoride through an integrated pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) and the World Health Organization (WHO) VigiBase. METHODS: Adverse event (AE) reports related to sodium fluoride were extracted from FAERS (2004-2024) and VigiBase (1971-2024). Reporting characteristics, including demographic distributions, reporter type, and event seriousness, were summarised descriptively. AEs were coded using the medical dictionary for regulatory activities (MedDRA) at the preferred term (PT) and system organ class (SOC) levels. Disproportionality-based signal detection was performed using multiple algorithms, and cross-database validation was applied to evaluate signal consistency and database-specific reporting features. RESULTS: Reporting patterns differed between the two systems: FAERS reports were predominantly submitted from the United States and by consumers, whereas VigiBase reports were mainly from Europe, with a higher proportion of health care professionals reporting. Reports involving female individuals were more frequently observed in both databases. Safety signals were primarily concentrated in oral and dental conditions, including dental fluorosis and acute oral mucosal reactions. Overall, 122 shared safety signals were identified across the two databases, with 62% involving oral or dental tissues. Adult populations accounted for a substantial proportion of reported signals, and a high proportion of reports were classified as serious, with predominantly early reported onset intervals. CONCLUSION: This dual-database pharmacovigilance analysis identified consistent sodium fluoride-associated safety signals with a predominant oral and dental focus, alongside notable geographic and demographic reporting differences. Cross-database validation highlighted complementary strengths of FAERS and VigiBase for global safety surveillance of fluoride-containing dental products. CLINICAL RELEVANCE: These findings support enhanced awareness of sodium fluoride-related safety patterns and may inform targeted monitoring strategies in preventive dental practice.