Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
PLoS One. 2019 Oct 8;14(10):e0217951. doi: 10.1371/journal.pone.0217951. eCollection 2019.
Many drugs can cause hearing loss, leading to sensorineural deafness. The aim of this study was to evaluate the risk of drug-induced hearing loss (DIHL) by using the Japanese Adverse Drug Event Report (JADER) database and to obtain profiles of DIHL onset in clinical settings. We relied on the Medical Dictionary for Regulatory Activities preferred terms and standardized queries, and calculated the reporting odds ratios (RORs). Furthermore, we applied multivariate logistic regression analysis, association rule mining, and time-to-onset analysis using Weibull proportional hazard models. Of 534688 reports recorded in the JADER database from April 2004 to June 2018, adverse event signals were detected for platinum compounds, sulfonamides (plain) (loop diuretics), interferons, ribavirin, other aminoglycosides, papillomavirus vaccines, drugs used in erectile dysfunction, vancomycin, erythromycin, and pancuronium by determining RORs. The RORs of other aminoglycosides, other quaternary ammonium compounds, drugs used in erectile dysfunction, and sulfonamides (plain) were 29.4 (22.4-38.6), 18.5 (11.2-30.6), 15.4 (10.6-22.5), and 12.6 (10.0-16.0), respectively. High lift score was observed for patients with congenital diaphragmatic hernia treated with pancuronium using association rule mining. The median durations (interquartile range) for DIHL due to platinum compounds, sulfonamides (plain), interferons, antivirals for treatment of hepatitis C virus (HCV) infections, other aminoglycosides, carboxamide derivatives, macrolides, and pneumococcal vaccines were 25.5 (7.5-111.3), 80.5 (4.5-143.0), 64.0 (14.0-132.0), 53.0 (9.0-121.0), 11.0 (3.0-26.8), 1.5 (0.3-11.5), 3.5 (1.3-6.8), and 2.0 (1.0-4.5), respectively. Our results demonstrated potential risks associated with several drugs based on their RORs. We recommend to closely monitor patients treated with aminoglycosides for DIHL for at least two weeks. Moreover, individuals receiving platinum compounds, sulfonamides (plain), interferons, and antivirals for HCV infection therapy should be carefully observed for DIHL for at least several months.
许多药物可导致听力损失，引起感音神经性聋。本研究旨在利用日本不良药物事件报告（JADER）数据库评估药物引起的听力损失（DIHL）的风险，并获得临床环境中 DIHL 发病的特征。我们依赖于监管活动医学词典首选术语和标准化查询，并计算报告比值比（ROR）。此外，我们应用多元逻辑回归分析、关联规则挖掘和使用威布尔比例风险模型的发病时间分析。在 2004 年 4 月至 2018 年 6 月期间，JADER 数据库中记录了 534688 份报告，通过确定 ROR 检测到铂化合物、磺胺类药物（普通）（袢利尿剂）、干扰素、利巴韦林、其他氨基糖苷类、人乳头瘤病毒疫苗、治疗勃起功能障碍的药物、万古霉素、红霉素和潘库溴铵的不良事件信号。通过 ROR 发现，其他氨基糖苷类、其他季铵化合物、治疗勃起功能障碍的药物和磺胺类药物的 ROR 分别为 29.4（22.4-38.6）、18.5（11.2-30.6）、15.4（10.6-22.5）和 12.6（10.0-16.0）。关联规则挖掘显示，接受潘库溴铵治疗先天性膈疝的患者高 lift 评分。铂化合物、磺胺类药物（普通）、干扰素、治疗丙型肝炎病毒（HCV）感染的抗病毒药物、其他氨基糖苷类、酰胺衍生物、大环内酯类和肺炎球菌疫苗引起的 DIHL 的中位持续时间（四分位距）分别为 25.5（7.5-111.3）、80.5（4.5-143.0）、64.0（14.0-132.0）、53.0（9.0-121.0）、11.0（3.0-26.8）、1.5（0.3-11.5）、3.5（1.3-6.8）和 2.0（1.0-4.5）。我们的结果基于 ROR 显示了与几种药物相关的潜在风险。我们建议至少两周密切监测接受氨基糖苷类药物治疗的患者的 DIHL。此外，接受铂化合物、磺胺类药物（普通）、干扰素和 HCV 感染治疗的抗病毒药物的个体应至少几个月密切观察 DIHL。
