Disproportionality analysis of cardiac adverse events associated with sorafenib using Spontaneous Reporting Database in Japanese

This study was conducted to examine the disproportionality, times to onset, incidence rates, and outcomes of sorafenib-associated cardiac AEs, using the Japanese Adverse Drug Event Report database. We analyzed 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). We analyzed 2,230,863 reports and identified 8,374 reports of AEs associated with sorafenib, including 318 cardiac AEs. Signals were detected for seven cardiac AEs: hypertension, cardiac failure congestive, myocardial infarction, acute myocardial infarction, angina pectoris, myocardial ischaemia, and angina unstable. Among these, fatal outcomes were observed for cardiac failure congestive, myocardial infarction, acute myocardial infarction, and myocardial ischaemia. Histograms of median times to onset for the seven detected cardiac AE signals showed that AEs occurred at a median of 9-159 days after sorafenib administration. Weibull distributions showed that the incidence of all these AEs occurred constantly throughout the exposure period (random failure type). In conclusion, we focused on cardiac AEs associated with sorafenib as post-marketing AEs. Some cases could experience serious outcomes after sorafenib administration. Patients should be monitored for signs of onset for these AEs not only at the start of administration, but also over an extended period.