Pharmacovigilance analysis of small bowel bleeding associated with NSAIDs.

Background: Currently, the factors influencing small bowel bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remain unclear.

Objectives: This study aimed to assess NSAID-associated small bowel bleeding and evaluate the impact of other drugs on it through a pharmacovigilance study, thereby providing valuable insights for clinical practice.

Design: Data on NSAID-associated small bowel bleeding were retrospectively extracted from two public adverse drug reaction databases-the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) and the Japan Pharmaceuticals and Medical Devices Agency's Adverse Drug Event Reporting (JADER)-from 2004 to 2023 for further analysis.

Methods: The reporting odds ratio (ROR), a pharmacovigilance technique, was employed to identify signals of adverse reactions, and the Chi-square test was utilized to assess differences between groups.

Results: Multiple NSAIDs associated with small bowel bleeding were identified in both databases. In the drug combination analysis, no significant differences in the risk of small bowel bleeding were found between NSAIDs combined with proton pump inhibitors (PPIs) and NSAIDs alone in FAERS (all p > 0.05). Decreasing risks were found when multiple NSAIDs were combined with rebamipide or probiotics compared to NSAIDs alone in JADER (p < 0.05 and ROR  < 1). In subgroup analyses of age and sex, older adults and males who used aspirin showed higher risk signals in both databases (all p < 0.05 and ROR  > 1).

Conclusion: PPIs did not show a significant impact on NSAIDs-associated small bowel bleeding, while rebamipide and probiotics may exhibited a preventive effect against NSAIDs-associated small bowel bleeding. Older adults and males constituted risk factors for aspirin-associated small bowel bleeding.