Disproportionality analysis of cardiac adverse events associated with lenvatinib using the Japanese Adverse Drug Event Report database

Aims: This study was conducted to examine disproportionality, times to onset, incidence rates and outcomes of lenvatinib-associated cardiac adverse events (AEs) using the Japanese Adverse Drug Event Report database.

Methods: We analysed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Furthermore, Weibull distribution parameters were calculated.

Results: Of the 2 230 863 reports analysed, we identified 7684 reports of AEs associated with lenvatinib, including 317 cardiac AEs. Signals were detected for eight cardiac AEs: hypertension, cardiac failure, myocarditis, myocardial infarction, immune-mediated myocarditis, cardiomyopathy, angina unstable and cardiotoxicity. Among these, fatal outcomes were observed for cardiac failure, myocarditis and myocardial infarction. Histograms of median times to onset for the eight detected cardiac AE signals showed that AEs occurred at a median of 3.5-134.5 days after lenvatinib administration. The Weibull distributions showed that cardiac failure occurred early after administration (early failure type), myocarditis occurred in a dose-dependent manner (wearout failure type), and myocardial infarction occurred constantly throughout the exposure period (random failure type).

Conclusions: We focused on cardiac AEs associated with lenvatinib as post-marketing AEs. Serious outcomes can arise after lenvatinib administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period.