Current Status of Adverse Events Related with Opioid Analgesics in Japan: Assessment Based on Japanese Adverse Drug Event Report Database

Opioid analgesics have greatly contributed to the advancement of pain management. However, although opioids have been appropriately used in Japan, they rarely induce serious adverse events, such as respiratory depression. The present study aimed to investigate the temporal changes in the occurrence of opioid-related adverse events and deaths between 2004 and 2017 in Japan using the Japanese Adverse Drug Event Report (JADER) database. We analyzed the following points using data extracted from JADER website: 1) temporal changes in the number and proportion of opioid-related adverse event reports; 2) temporal changes in the number of morphine-, oxycodone-, and fentanyl-related adverse event reports per annual consumption; and 3) cases in which the reported outcome following opioid-related adverse events was death. Our results showed no dramatic changes in the overall incidence of opioid-related adverse events, despite the temporal changes in the annual consumption and shared component of each opioid during the survey period. However, the number and rate of fentanyl-related adverse events and their outcome "death" increased since 2010, being the highest among all adverse event including those related to morphine and oxycodone. Outcome "death" by fentanyl-related adverse events was caused mainly due to respiratory depression. These findings suggest that, although opioid-related adverse events can be controlled through proper monitoring and management by medical personnel in Japan, extra caution should be continuously paid for the rare but serious fentanyl-induced adverse events.