Safety Evaluation of Nitroimidazole Antibiotics Based on the FAERS Database

ABSTRACT Nitroimidazole antibiotics, including metronidazole, tinidazole, and ornidazole, are widely used to treat anaerobic infections and parasitic diseases. Although their efficacy is well established, comprehensive safety profiles—particularly concerning rare adverse events—remain incompletely elucidated. This study aimed to systematically evaluate the safety signals of these drugs using the FDA adverse event reporting system (FAERS) database from 2014 to 2024. Disproportionality analyses were performed at the system organ class (SOC) and standardised MedDRA queries (SMQ) levels to identify associations between nitroimidazole antibiotics and adverse events. A total of 17,631 adverse event reports were analysed for metronidazole, tinidazole, and ornidazole, respectively. Females comprised the majority of reports (57.35%, 51.70%, and 61.11%, respectively), which may reflect the common use of these agents in gynaecological infections. Metronidazole was associated with the shortest median time to onset of adverse events (2.5 days), while tinidazole had the longest (5.5 days). At the SOC level, all three drugs showed positive associations with gastrointestinal, nervous system, and cardiac disorders. Ornidazole showed strong disproportionality signals for vascular (IC 025 = 18.46) and skin disorders (IC 025 = 17.46), while tinidazole was associated with weaker but notable signals for skin and blood disorders. Notably, SMQ‐level analysis uncovered significant safety signals not currently emphasised in drug labelling, including acute pancreatitis, hepatic failure, fibrosis/cirrhosis, and tachyarrhythmias for tinidazole and ornidazole. These findings highlight the potential need for intensified clinical monitoring of hepatic and cardiac function during treatment with these antibiotics. Although limited by the nature of spontaneous reporting data, this study offers important insights into both established and emerging risks associated with nitroimidazole antibiotics, reinforcing the value of continuous pharmacovigilance to optimise patient safety.