McColley Susanna A
a Feinberg School of Medicine , Northwestern University , Chicago , IL , USA.
b Clinical and Translational Research, Stanley Manne Children's Research Institute , Ann & Robert H. Lurie Children's Hospital of Chicago , Chicago , IL , USA.
Expert Opin Drug Saf. 2016 May;15(5):709-15. doi: 10.1517/14740338.2016.1165666. Epub 2016 Apr 7.
Ivacaftor is indicated for treatment of cystic fibrosis (CF) mediated by 10 mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that causes gating or partial function abnormalities. In placebo-controlled and open-label studies, ivacaftor-treated subjects showed improved pulmonary function, nutrition and quality of life measures. This article reviews ivacaftor safety.
Safety findings in ivacaftor clinical trials, and reported subsequently, were accessed by a PubMed search using key words "VX-770" or "ivacaftor". Additional information was accessed via Google Search. Transaminitis was noted in ivacaftor and combination lumacaftor-ivacaftor trials. Ivacaftor was associated with cataracts in juvenile rat pups in pre-clinical studies; non-congenital cataracts have been found in children taking ivacaftor. Ivacaftor is a CYP3A substrate; CYP3A inhibitors and inducers should be avoided during its administration. Ivacaftor and its M1 metabolite may inhibit CYP3A and P-gp; therefore, ivacaftor may increase systemic exposure to drugs which are substrates of CYP3A and/or P-gp, increasing the potential for adverse events.
Ivacaftor therapy may be associated with ocular and hepatic side effects; specific recommendations for monitoring are available. Potential drug interactions should be evaluated in patients taking ivacaftor. High clinical efficacy suggests that the risk benefit ratio of ivacaftor favors therapy.
依伐卡托适用于治疗由囊性纤维化跨膜传导调节因子（CFTR）基因的10种突变介导的囊性纤维化（CF），这些突变会导致门控或部分功能异常。在安慰剂对照和开放标签研究中，接受依伐卡托治疗的受试者肺功能、营养状况和生活质量指标均有所改善。本文综述依伐卡托的安全性。
通过使用关键词“VX-770”或“依伐卡托”在PubMed上进行检索，获取依伐卡托临床试验及后续报道中的安全性研究结果。通过谷歌搜索获取更多信息。在依伐卡托及鲁马卡托-依伐卡托联合治疗试验中发现了转氨酶升高。临床前研究发现依伐卡托与幼年大鼠幼崽的白内障有关；服用依伐卡托的儿童中发现了非先天性白内障。依伐卡托是CYP3A的底物；给药期间应避免使用CYP3A抑制剂和诱导剂。依伐卡托及其M1代谢产物可能会抑制CYP3A和P-糖蛋白；因此，依伐卡托可能会增加CYP3A和/或P-糖蛋白底物药物的全身暴露，增加不良事件发生的可能性。
依伐卡托治疗可能与眼部和肝脏副作用有关；有可用的具体监测建议。服用依伐卡托的患者应评估潜在的药物相互作用。较高的临床疗效表明依伐卡托的风险效益比有利于治疗。
