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. 2025 May 6:16:20420986251318848.
doi: 10.1177/20420986251318848. eCollection 2025.

Pharmacovigilance analysis of small bowel bleeding associated with NSAIDs

Ying-Han Deng  1 , Meiting Jiang  1 , Yun Chen  1 , Hong-Bin Chen  2
Affiliations

Pharmacovigilance analysis of small bowel bleeding associated with NSAIDs

Ying-Han Deng et al. Ther Adv Drug Saf. .

Abstract

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.

Keywords: NSAIDs; PPIs; probiotics; rebamipide; small bowel bleeding.

Plain language summary

Intestine bleeding with NSAIDs This pharmacovigilance study analyzed U.S. and Japanese drug adverse event databases (2004–2023) to evaluate NSAID-related small bowel bleeding risks. Results showed that combining NSAIDs with proton pump inhibitors (PPIs) did not reduce bleeding risk, but pairing NSAIDs with mucosal protective agents (e.g., rebamipide) or probiotics significantly lowered risk in Japanese data. Elderly males emerged as a high-risk population for NSAID-related small bowel bleeding, requiring heightened clinical attention. These findings highlight the potential of mucosal protective agents for preventing NSAID-induced intestinal injury, with probiotics showing particular promise for further exploration. Meanwhile, the impact of PPIs in this risk warrants additional validation.

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Figures

Figure 1.
Figure 1.
Adverse drug reaction screening flowchart.
Figure 2.
Figure 2.
Signaling of NSAIDs-associated small intestinal bleeding adverse reactions in FAERS and JADER. FAERS, Food and Drug Administration’s Adverse Event Reporting System; JADER, Japan Pharmaceuticals and Medical Devices Agency’s Adverse Drug Event Reporting; NSAID, nonsteroidal anti-inflammatory drug.
See this image and copyright information in PMC

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