Belai Natnael, Gebrehiwet Selamawit, Fitsum Yodit, Russom Mulugeta
Orotta National Referral Hospital, Asmara, Eritrea.
Eritrean Pharmacovigilance Centre, Asmara, Eritrea.
J Med Case Rep. 2018 May 20;12(1):135. doi: 10.1186/s13256-018-1580-8.
Hydrochlorothiazide is not known to cause hearing disorder. The Eritrean Pharmacovigilance Centre, however, has received cases of hearing disorder, including irreversible deafness, associated with hydrochlorothiazide. The aim of this study is, therefore, to assess the causal relationship between hydrochlorothiazide and hearing disorder.
Data was retrieved from the WHO global adverse drug reaction database, VigiBase™. A search on VigiBase™ was made on August 6, 2017 using "hydrochlorothiazide" as drug substance, and "ototoxicity", "decreased hearing", and "vestibular disorder" as reaction terms. Cases were retrieved using VigiLyze™ and exported to an Excel spreadsheet for descriptive analysis. Causality was assessed using Austin Bradford-Hill criteria and labeledness of the reaction was evaluated through a thorough literature review including the summary of product characteristics.
From 1972 to August 2017, 94 cases of hearing disorder associated with hydrochlorothiazide were submitted from 18 countries to VigiBase™. The median age was 64 years with almost equal male to female ratio. In 53.2% of the cases, hydrochlorothiazide was reported as the only suspected drug. Of these, 26 cases encountered hearing disorder following the sole intake of hydrochlorothiazide. Reaction was marked as "serious" in 36% of the cases and median time to reaction onset was 3 days. Outcome was reported as reversible in 66.7% of the cases. Reaction resolved in 17 cases following withdrawal of hydrochlorothiazide and recurred in one case after subsequent rechallenge with the product. Consistency of cases and a dose-response relationship was also observed in this case series.
This case series assessment found a suggestive causal relationship between hydrochlorothiazide and hearing disorder. Taking the inherent limitations of this study into account, results should be interpreted with caution and further studies are required to validate the safety signal.
目前尚不清楚氢氯噻嗪会导致听力障碍。然而，厄立特里亚药物警戒中心收到了与氢氯噻嗪相关的听力障碍病例，包括不可逆性耳聋。因此，本研究的目的是评估氢氯噻嗪与听力障碍之间的因果关系。
从世界卫生组织全球药品不良反应数据库VigiBase™中检索数据。2017年8月6日在VigiBase™上进行搜索，使用“氢氯噻嗪”作为药物名称，“耳毒性”、“听力下降”和“前庭障碍”作为反应术语。使用VigiLyze™检索病例并导出到Excel电子表格进行描述性分析。使用奥斯汀·布拉德福德·希尔标准评估因果关系，并通过全面的文献综述（包括产品特性摘要）评估反应的标注性。
从1972年到2017年8月，18个国家向VigiBase™提交了94例与氢氯噻嗪相关的听力障碍病例。中位年龄为64岁，男女比例几乎相等。在53.2%的病例中，氢氯噻嗪被报告为唯一可疑药物。其中，26例在单独服用氢氯噻嗪后出现听力障碍。36%的病例反应被标记为“严重”，反应开始的中位时间为3天。66.7%的病例报告结果为可逆。17例在停用氢氯噻嗪后反应消失，1例在随后再次使用该产品后复发。在该病例系列中还观察到病例的一致性和剂量反应关系。
该病例系列评估发现氢氯噻嗪与听力障碍之间存在提示性因果关系。考虑到本研究的固有局限性，结果应谨慎解释，需要进一步研究来验证该安全信号。
