Data Mining of the Japanese Adverse Drug Event Report Database and Animal Experiments for Assessment of Risks Associated With Pemafibrate

BACKGROUND/AIM: Pemafibrate is a novel and selective peroxisome proliferator-activated receptor α modulator that has demonstrated favorable efficacy and safety in phase II or III trails. Compared to fenofibrate, a conventional fibrate, pemafibrate exerts a triglyceride-lowering effect at 1/500 of the dose, and the incidence rate of adverse drug reactions is one-ninth at these doses. The aim of this study was to obtain additional information on the safety of pemafibrate. PATIENTS AND METHODS: The Japanese Adverse Drug Event Report (JADER) database was analyzed, and the associations of three fibrates and six statins with rhabdomyolysis and acute renal failure were evaluated using reporting odds ratios and information components. Additionally, preclinical experiments were conducted in rats. Creatine phosphokinase (CK) levels were measured after a single administration of fibrates. The CK levels were also assessed when pemafibrate was co-administered with statins. RESULTS: Data mining of the JADER database suggested associations between all fibrates and statins and rhabdomyolysis; however, no signal for acute renal failure was detected for pemafibrate. Signals for rhabdomyolysis were observed for some fibrates when combined with statins, whereas no signal was detected for pemafibrate. In rats, outlier CK levels were not observed after pemafibrate administration, and no significant increase was observed. CK levels were significantly increased by pravastatin treatment. CONCLUSION: The JADER analysis suggests that pemafibrate may be a safer alternative to conventional fibrates, with a potentially lower association with rhabdomyolysis and acute renal failure, even when co-administered with statins. Preclinical animal experiments support the results of the JADER analysis. However, large-scale prospective studies are needed to clarify the risks of pemafibrate.