Drug-induced tubulointerstitial nephritis in a retrospective study using spontaneous reporting system database

Abstract

IntroductionTubulointerstitial nephritis (TIN) is a problem in clinical settings because drug therapy is the cause in most cases. Patients often present with nonspecific symptoms, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of TIN with the causative drugs using a spontaneous reporting system database.Materials and methodsData were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on 5,195,890 reports of all adverse reactions, we obtained 3,088 reports of TIN caused by all drugs and calculated the reporting odds ratio (ROR) and 95% CI for TIN.ResultsThe 5 drugs with the highest RORs were gliclazide (ROR, 30.5; 95% CI, 17.4–53.2), tosufloxacin tosilate hydrate (ROR, 29.5; 95% CI, 21.3–41.0), piperacillin–tazobactam (ROR, 24.3; 95% CI, 19.4–30.5), cefteram pivoxil (ROR, 23.5; 95% CI, 12.5–44.2), and mefenamic acid (ROR, 22.5; 95% CI, 13.4–37.7). No sex-related difference was observed in drug-induced TIN. Most of the reports about TIN onset following the administration of culprit drugs were recorded within 12 weeks.ConclusionBased on the results, a comprehensive study using a pharmacovigilance database enabled us to identify the dugs that most frequently induced TIN, so these drugs should be used carefully in clinical practice to avoid TIN.

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.…”