Risk Analysis of Drug-induced Acute Pancreatitis Using Japanese Adverse Drug Event Report Database

Abstract

We investigated the relationship between drug administration and the onset of acute pancreatitis using the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency. Upon analysis of the proportional reporting ratio, an indicator of signal detection in pharmacovigilance, signals were detected for 65 drugs such as L-asparaginase, mesalazine, and estrogen among 1,129,350 reports in JADER. Data suggest that the younger age groups have a higher risk of acute pancreatitis for 7 drugs including L-asparaginase and azathioprine, as do men compared to women for 4 drugs including telaprevir and sodium valproate. In analysis of the time-to-onset profile using Weibull distribution, 6 drugs including L-asparaginase and mesalazine were estimated to be the early failure type, and peginterferon alfa-2b and telaprevir were estimated to be the wear out failure type. Logistic regression analysis showed a significant association between the presence of concomitant drugs and the onset of acute pancreatitis for 4 drugs namely L-asparaginase, azathioprine, tacrolimus, and methylprednisolone sodium succinate. These results will be useful for monitoring acute pancreatitis induced by drugs.