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

Abstract

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 fentanylinduced adverse events.

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

“…Although tramadol and tapentadol are claimed to have better safety profiles than their opioid peers, several adverse events have been reported, including nausea, vomiting, dizziness, seizures, dyspnea, respiratory depression [ 1 , 2 , 14 , 47 , 48 , 49 , 50 , 51 ], and even fatal cases [ 10 , 42 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. In the VigiBase™ World Health Organization (WHO) Global Database of Individual Case Safety Reports concerning 5-HT toxicity, tramadol ranks 1st and tapentadol ranks 3rd (with 647 and 115 cases out of 1641, respectively) as the only suspected cause or amongst other drugs, and 1st and 2nd (with 62 and 42 cases out of 147, respectively) as the only suspected cause [ 34 , 69 ].…”

Prevalence of and Risk Factors for Prescription Opioid Misuse, Abuse, Diversion and Doctor Shopping in Japan: A Survey Study

“…The Global Burden of Disease Study 2017 estimated that, in North America, OUD accounts for more than 4 million healthy years of life lost due to disability and premature death [ 29 ]. Although Japan has largely avoided the dramatic surge in opioid consumption and related adverse outcomes witnessed in other countries [ 30 ], the relatively high prevalence of misuse and abuse reported by survey participants, at 45.5% and 24.5%, respectively, suggests a need for greater awareness among medical professionals to detect inappropriate opioid use early and prevent OUD. In contrast to other countries which have established harm reduction strategies for OUD, treatment of OUD has not been approved in Japan, making it difficult to provide opioid maintenance treatment, and detoxification is available only at some psychiatric institutions.…”

Pharmacovigilance Evaluation of Bendamustine-related Skin Disorders using the Japanese Adverse Drug Event Report Database

“…Data from released JADER database (15)(16)(17). This database is available for free download from the PMDA website (http://www.pmda.go.jp) and includes ADE cases.…”

“…In April 2004, Japan's Pharmaceuticals and Medical Devices Agency (PMDA) established a spontaneous reporting system. The Japanese Adverse Drug Event Report (JADER) database is a large-scale, unitized database for pharmacovigilance that accumulates reported cases and their results (15)(16)(17). To our knowledge, the present study is the first report to analyze the relevant characteristics of skin disorders in bendamustinetreated patients using a database of adverse events reported spontaneously in Japan.…”