Differential profiles of adverse events associated with mycophenolate mofetil between adult and pediatric renal transplant patients

Abstract

ObjectiveImmunosuppressive regimens after renal transplantation usually include a combination of calcineurin inhibitors, corticosteroids, and a proliferation inhibitor, either azathioprine or mycophenolate mofetil (MMF), to prevent rejection and maintain graft function. MMF has a stronger immunosuppressive effect than does azathioprine. This study aimed to examine MMF-associated adverse events in renal transplant patients.MethodsRetrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database.ResultsA total of 11,594 adverse drug events were reported in renal transplant patients; 10,272 (88.6%) involved adults and 1322 (11.4%) involved children. In adult patients, the most frequent adverse events induced by MMF were cytomegalovirus infection (272 reports), urinary tract infection (69 reports), and polyomavirus-associated nephropathy (61 reports). Among adverse events, the highest reporting odds ratio (ROR) was found for cytomegalovirus infection (ROR, 1.58; 95% confidence interval, 1.36–1.83). In pediatric patients, the rank order for MMF-associated adverse events was cytomegalovirus infection (27 reports), bronchitis (23 reports), and cytomegalovirus viremia (19 reports), but these adverse events were not detected as a signal.ConclusionOur results show the safety profile of MMF in pediatric renal transplant patients. These findings can be used to update information used for prescriptions for pediatric patients.

Association of Stevens‐Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs in pediatric patients: Subgroup analysis based on a Japanese spontaneous database

“…The present study used data from the public release of PMDA’s JADER database as a large spontaneous reporting database, from which adverse event reports voluntarily submitted to the PMDA between April 2004 and January 2017 are freely available. The data structure of the JADER consists of four datasets: patient demographic information (DEMO), drug information (DRUG), adverse events (REAC) and medical history (HISTO).…”

“…We compiled a cross‐tabulation table based on two classifications: the presence or absence of the adverse event, and the presence or absence of the suspected medicine. Then, we calculated the ROR as reported previously . The ROR is the rate of reporting a specific adverse event caused by a particular drug divided by the rate of the same adverse event caused by all other drugs present in the database.…”

“…Therefore, unexpected and serious adverse events are sometimes encountered in post‐marketing reports, so pharmacovigilance activities are important to reveal them. In April 2004, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) established a spontaneous reporting system, the Japanese Adverse Drug Event Report (JADER) database, a unitized large‐scale database for pharmacovigilance . The objective of this study was to analyse the characteristics of SJS and TEN associated with AEDs in pediatric patients using a spontaneously reported adverse drug events database in Japan.…”

“…The present study used data from the public release of PMDA's JADER database as a large spontaneous reporting database, 11,[13][14][15] from which adverse event reports voluntarily submitted to the PMDA between April 2004 and January 2017 are freely available.…”

“…Then, we calculated the ROR as reported previously. 11,[13][14][15] The ROR is the rate of reporting a database. In addition, the ROR was frequently used in spontaneous reporting databases as an index of the relative risk of drug-associated adverse events.…”