Naunyn Schmiedebergs Arch Pharmacol. 2026 Apr 15. doi: 10.1007/s00210-026-05302-z. Online ahead of print.
ABSTRACT
Dyslipidemia is a critical risk factor for cardiovascular disease, underpinning the widespread clinical application of fibrates. Given their increasing utilization, a comprehensive evaluation of their safety profiles is warranted. Data were extracted from the FDA Adverse Event Reporting System (FAERS) database. This study interrogates a large pharmacovigilance database spanning over 20 years to assess the real-world safety of fenofibrate and gemfibrozil and identify significant adverse event (AE) signals. Adverse event data for fenofibrate and gemfibrozil were collected from the first quarter of 2004 to the second quarter of 2025. Following standardization, signal quantification techniques (ROR, PRR, BCPNN, and EBGM) were applied for analysis, with additional assessments of gender- and age-based differences. Our analysis identified 5751 and 31,738 AEs reports associated with fenofibrate and gemfibrozil, respectively. AEs for both fenofibrate and gemfibrozil spanned 27 system organ classes (SOCs). Fenofibrate AEs were primarily related to musculoskeletal and metabolic disorders. In contrast, gemfibrozil was predominantly associated with haemorrhagic and thrombotic complications, affecting the vascular, gastrointestinal, and nervous systems. Despite these differences, both drugs exhibited a similar biphasic pattern in their time to onset of AEs. The concomitant use of gemfibrozil with interacting medications, specifically statins (increasing the risk of severe rhabdomyolysis) and oral anticoagulants (elevating bleeding risk), was more frequently reported than for fenofibrate. This study reveals distinct safety differences between fenofibrate and gemfibrozil, highlighting the need for individualized monitoring and careful clinical management. Future research should clarify the underlying mechanisms and develop targeted interventions to improve patient outcomes.
PMID:41984191 | DOI:10.1007/s00210-026-05302-z