Purpose: The aim of the present study was to elucidate the trends in drug interactions for pharmaceutical products in Japan by examining safety profile updates.
Methods: All 12 422 prescription drugs currently on the Japanese market were included in the study. Revisions to their product information (or package insert: PI) were investigated from January 2000 to December 2003. The publication 'Drug Safety Update,' which is a summary of the revisions made to the precautions in PIs and is issued by The Society of Japanese Pharmacopoeia and The Federation of Pharmaceutical Manufacturers' Associations of Japan under the supervision of the Ministry of Health, Labour and Welfare (MHLW), was used as a data source. The revised drug interactions were categorized according to measures, mechanisms, and evidence from published references.
Results and conclusions: The results revealed 426 new interactions, including 75 contraindicative combinations, during the survey period. About 45% and 27% of the new interactions involved metabolic and pharmacological processes, respectively, with metabolic interactions involving cytochrome P450 3A4 being the dominant reason for the revision of PIs. Only 37% of the new interactions cited scientific journals and/or books, and 58% of these references cited were published more than 5 years prior to the date of revision. In conclusion, metabolic interactions were the major reasons for the update of safety information after 2000. Published references should be provided in order to assist with clinical management and avoid the undesirable effects of new drug interactions.