Safety signals of amide local anesthetics in dentistry: a real-world data analysis

Background Amide local anesthetics (LAs) are essential for dental pain management, yet their real-world safety profiles, particularly regarding rare adverse events (AEs) and demographic disparities, remain under-characterized. This study aimed to evaluate the real-world safety profiles of the commonly used amide LAs in dentistry. Methods AE data from the FAERS (2004Q1-2025Q2) were analyzed, and dental-related reports were extracted using dental keywords. Pharmacovigilance signals for amide LAs, including lidocaine, articaine, bupivacaine, mepivacaine, and prilocaine, were detected using the reporting odds ratio (ROR) method. Results A total of 3203 dental-related AE reports were identified, primarily involving lidocaine and articaine. Disproportionality analysis revealed drug-specific signals: lidocaine in “cardiac disorders”; articaine and mepivacaine in “nervous system disorders”. Females reported more AEs, while males had higher fatality rates with bupivacaine and mepivacaine. Serious AEs followed a “boat-shaped” age distribution, with higher proportions in children (≤ 3 years) and the elderly (≥ 75 years). Children under 4 years treated with lidocaine showed a much higher risk of seizure, cardiac arrest, and methemoglobinemia (ROR > 50). Notably, 60 new signals were identified across three anesthetics, specifically showing that lidocaine was associated with severe systemic and neurological events, articaine with localized cranial nerve disturbances, and mepivacaine with potent signals for facial nerve dysfunction. Bupivacaine showed the highest reporting proportion for fatal outcomes. Conclusion Amide LAs commonly used in dentistry exhibited sex-, age-, and agent-dependent safety profiles. This study highlights the importance of selecting an appropriate anesthetic agent based on individual patient characteristics to ensure safety during dental practice.