Differences in Reported Anaphylaxis Associated with Common Nonsteroidal Anti-Inflammatory Drugs: A Pharmacovigilance Study.

Abstract

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of drug hypersensitivity reactions, yet comparative real-world data on drug-specific anaphylaxis reporting remain limited. This study aimed to evaluate reporting patterns and disproportionality signals of NSAID-associated anaphylaxis in the FDA Adverse Event Reporting System (FAERS), compare severe outcomes across individual NSAIDs, and describe the indication context of these reports.

Methods: In this cross-sectional pharmacovigilance study, FAERS reports from 2015Q1 to 2025Q2 were analyzed. Five NSAIDs were included: ibuprofen, diclofenac, naproxen, celecoxib, and meloxicam. Anaphylaxis was defined by 4 MedDRA preferred terms and restricted to reports listing the target NSAID as the primary suspect drug. Disproportionality was assessed using reporting odds ratio, proportional reporting ratio, empirical Bayes geometric mean, and information component.

Results: Total adverse event reports were 51,837 for ibuprofen, 43,979 for diclofenac, 27,043 for naproxen, 13,085 for celecoxib, and 2,591 for meloxicam. Corresponding anaphylaxis reports were 938 (1.81%), 919 (2.09%), 320 (1.18%), 178 (1.36%), and 38 (1.47%). All 5 NSAIDs showed disproportionality signals versus all other drugs. Female predominance was observed across agents. Most reports involved adults aged 18-64 years, except meloxicam, which was concentrated in those aged 65-85 years. Diclofenac reports mainly originated outside the USA, whereas naproxen had the highest proportion of US reports. Among submitted FAERS reports of NSAID-associated anaphylaxis, the reported proportion of DE/LT outcomes varied across the 5 NSAIDs. Pain and back pain were common indications, but the broader indication patterns showed drug-specific features.

Conclusion: NSAIDs showed consistent disproportionality signals for anaphylaxis in FAERS, with observable heterogeneity in reporting patterns across individual agents.