Lower Gastrointestinal Adverse Events with Naproxen/Esomeprazole: A Disproportionality Analysis Using the WHO Pharmacovigilance Database

Objective: This study evaluated the reporting patterns of lower gastrointestinal adverse events (LGI-AEs) associated with nonsteroidal anti-inflammatory drug (NSAID)/proton pump inhibitor (PPI) combination therapy compared with NSAID monotherapy and cyclooxygenase-2 selective inhibitors (COX-2 SIs) using VigiBase, a global adverse event (AE) database.Methods: A disproportionality analysis was conducted using individual case safety reports (ICSRs) recorded in VigiBase from 2010 to 2024.The study drug was naproxen/esomeprazole, with all other NSAIDs as the primary comparator and COX-2 SIs as the secondary comparator.Reporting odds ratios (RORs) and 95% confidence intervals (CIs) were calculated for LGI-AEs.A signal was defined as ROR 1 with 2 4 and at least three reports.Results: Among 4,641,540 drug-AE pairs, 22,627 were associated with the study drug, with 135 LGI-AEs.The ROR for LGI-AEs was 0.71 (95% CI: 0.60-0.84)compared with all other NSAIDs, and 0.78 (95% CI: 0.64-0.95)compared with COX-2 SIs.Conclusion: Naproxen/esomeprazole showed a lower disproportionality signal for LGI-AEs compared to other NSAIDs and COX-2 SIs.These results suggest a different reporting pattern but do not imply reduced risk or causality.Further studies are needed to validate these findings.(