Signal Detection Study Focusing on Differences in the Drug Delivery System of Oral 5-Aminosalicylate for Inflammatory Bowel Disease Using the Japanese Pharmacovigilance Database

Abstract

Although 5-Aminosalicylate (5-ASA) has been shown to act on the local mucosa, when 5-ASA is orally administered, most of it is absorbed in the upper gastrointestinal tract and does not reach the large intestine, where lesions are present. Therefore, different drug delivery systems have been developed for each oral 5-ASA formulation. Currently, the oral 5-ASA formulation approved in Japan is salazosulfapyridine (SALAZOPYRIN®; Pfizer Japan Inc.: Tokyo, Japan), in which 5-ASA and sulfapyridine are azo-bonded. In addition, there are several 5-ASA release formulations, including ASACOL®; ZERIA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH), PENTASA®; KYORIN Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on time), and LIALDA®; MOCHIDA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH and time). Adverse events may occur because of differences in the drug delivery systems of these products. In this study, we focused on the adverse events of different 5-ASA formulations and investigated differences in the detection of safety signals for each 5-ASA formulation using disproportionality analysis. There were 15 adverse events detected only with SALAZOPYRIN®. On the other hand, ASACOL®, PENTASA®, and LIALDA® have different drug delivery systems. Although the detected signal intensities varied, the detected adverse events were not significantly different. These findings provide important insights, which should be considered by physicians during treatment selection and drug manufacturers during drug development.

Keywords

• 5-Aminosalicylate
• drug delivery systems
• safety signal
• disproportionality analysis
• Japanese Ad-verse Drug Event Report database (JADER)