Evaluation of cardiac toxicity with ponatinib using a spontaneous reporting database

Abstract

This study aimed to determine the risk of ponatinib-induced cardiac toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on cardiac toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 1,152 reports of AEs caused by ponatinib. Of these, 163 cardiac toxicities were reportedly associated with ponatinib. Signals were detected for thirteen cardiac toxicities: hypertension, cardiac failure, acute cardiac failure, atrial fibrillation, increased blood pressure, coronary artery stenosis, myocardial infarction, angina pectoris, pulmonary hypertension, prolonged QT on electrocardiography, cardiomyopathy, cardiac dysfunction, and acute myocardial infarction. Among these, hypertension was the most frequently reported AE (27.6%). A histogram of times to onset showed occurrence from 4.5 to 150.5 days. Hypertension, cardiac failure, coronary artery stenosis, and myocardial infarction could potentially result in serious outcomes and some cases occurred earlier or even more than 1 year after starting administration. In conclusion, patients should be monitored for signs of the onset of these AEs not only at the start of ponatinib administration but also over the longer term.

Evaluation of Cardiac Adverse Events with Ponatinib Using a Spontaneous Reporting Database

“…We used data from public releases of the JADER [11][12][13][14][15]. This database is freely available for download from the PMDA Website (https://www.pmda.go.jp/english/index.html, https://www.info.…”