Pharmacovigilance Assessment of Drug-Induced Acute Pancreatitis Using a Spontaneous Reporting Database

Abstract

Background: Acute pancreatitis (AP) is associated with risks of morbidity and mortality. The incidence of AP recently increased compared to that traditionally reported in the literature. Objective: The purpose of this study was to evaluate the possible association between AP and drugs using the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database of adverse drug events. Methods: Adverse event reports submitted to the JADER database between 2004 and 2017 were analyzed. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence intervals for signal detection. Results: A total of 3,443 reports (0.17% of all adverse events) were identified as drug-induced AP, in which 431 different drugs were involved. Acute pancreatitis was frequently reported in men (58.5%) in their 60s (19.1%); 40.6% developed AP within 4 weeks after the treatment. Among the most frequently reported drugs, signals were detected for prednisolone, ribavirin, sitagliptin, mesalazine, tacrolimus, and l-asparaginase, which are well-known causes of AP. Telaprevir, donepezil, and ustekinumab also generated signals. As for drugs with high RORs, l-asparaginase and alogliptin were noteworthy. Conclusion: Most of the identified drugs were already known to induce AP, but the likelihood of the reporting of AP varied among the drugs. Our results should raise physicians’ awareness of drugs associated with AP, but further investigation of these medications is warranted.

Immunosuppressant-induced late acute pancreatitis after laparoscopic sleeve gastrectomy: a case report and literature review

“…In the literature, Azathioprine is the only immunosuppressant drug with solid evidence of being a cause of pancreatitis, while others like Tacrolimus and MMF are not yet proven [5, 10]. Tacrolimus, which is known as Envarsus, fujimycin or FK506, is commonly used in the last 20 years as an immunosuppressant to lower the rate of rejection with a variety of adverse effects, including neurotoxicity, hepatotoxicity, nephrotoxicity and infection [9]. Junnan Xu et al .…”

“…Einollahi et al . report one of the rare early cases linked directly to MMF as a cause of AP after renal transplant [9, 10].…”

“…Iku Niinomi et al . used the Japanese Adverse Drug Event Report database to point out the most frequently reported drugs to cause AP including Prednisolone (180 reports), and most importantly Tacrolimus (105 reports) [9]. They reported as well that around 40.6% of drug-induced AP was within 4 weeks after the treatment [9], but there is no data about late AP induced by immunosuppressants.…”

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

“…patient demographic information (DEMO), drug information (DRUG), adverse events (REAC), and medical history. The DEMO table was then linked to the DRUG and REAC tables using the ID number, as reported previously [7,9,11]. The contribution of the medication to adverse events was classified into three categories: "suspected medicine," "concomitant medicine," and "interaction."…”

Priapism and Second‐Generation Antipsychotics: Disproportionality Analysis of a Spontaneous Reporting System Database in Japan

“…We used reporting odds ratios (RORs) to compare the reporting frequency of priapism between individual SGAs. ROR is a validated effect measure for safety signal detection 4 and has been frequently used in spontaneous reporting databases as a safety signal index 5 . In this study, the ROR is the ratio of the odds of reported priapism to all other adverse events associated with a certain SGA compared with another SGA.…”