Salem M, Reichlin T, Fasel D, Leuppi-Taegtmeyer A
Department of Clinical Pharmacology and Toxicology, University & University Hospital Basel, Switzerland.
Department of Cardiology, University Hospital Basel, Switzerland.
Glob Cardiol Sci Pract. 2017 Jun 30;2017(2):11. doi: 10.21542/gcsp.2017.11.
Literature about torsade de pointes induced by azole antifungal agents is scarce, despite the well-known association. Furthermore, little is known about the latency time between commencing an azole antifungal agent and developing torsade de pointes. The objectives of the present study were therefore to identify all cases of torsade de pointes associated with systemic azole antifungal use reported to the WHO monitoring centre (Uppsala, Sweden) and to determine the latency times between commencing the azole and developing torsade de pointes. Investigator-driven, retrospective, descriptive analysis of post-marketing pharmacovigilance data regarding systemic azole antifungal agents and the development of torsade de pointes reported to the WHO monitoring centre 1995-2015. 191 cases were reported as follows: fluconazole 130, itraconazole 22, ketoconazole 5, posaconazole 1, voriconazole 33. More than half of all cases involved concomitant suspected or interacting drugs. The median latency times between starting the azole and developing torsade de pointes ranged from 1 (posaconazole) - 9.5 days (itraconazole), range <1-250). Clinicians should be aware of these features of azole-associated torsade de pointes, avoid interacting drugs if at all possible and monitor at-risk patients.
尽管唑类抗真菌药与尖端扭转型室速之间的关联已为人熟知，但关于此类药物所致尖端扭转型室速的文献却很匮乏。此外，对于开始使用唑类抗真菌药至发生尖端扭转型室速之间的潜伏期，人们了解甚少。因此，本研究的目的是确定向世界卫生组织监测中心（瑞典乌普萨拉）报告的所有与全身性唑类抗真菌药使用相关的尖端扭转型室速病例，并确定开始使用唑类药物至发生尖端扭转型室速之间的潜伏期。对1995年至2015年期间向世界卫生组织监测中心报告的有关全身性唑类抗真菌药及尖端扭转型室速发生情况的上市后药物警戒数据进行研究者驱动的回顾性描述性分析。共报告了191例病例，具体如下：氟康唑130例、伊曲康唑22例、酮康唑5例、泊沙康唑1例、伏立康唑33例。所有病例中半数以上涉及可疑的相互作用药物。开始使用唑类药物至发生尖端扭转型室速的中位潜伏期为1天（泊沙康唑）至9.5天（伊曲康唑）（范围<1至250天）。临床医生应了解唑类相关尖端扭转型室速的这些特征，尽可能避免使用相互作用药物，并对高危患者进行监测。
