The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis.
The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis.
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DOI：
10.1080/14740338.2017.1372419
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发表时间：
2017-11
影响因子：
3.1
通讯作者：
McColley SA
中科院分区：
文献类型：
--
作者：
Talamo Guevara M;McColley SA
Lumacaftor-ivacaftor 适用于治疗 Phe-508del 囊性纤维化跨膜电导调节因子 (CFTR) 基因突变纯合患者的囊性纤维化 (CF)。在临床试验中，接受治疗的患者表现出肺功能的改善、肺部症状的减轻以及其他益处。本文回顾了这种疗法的安全性。 PubMed 和 Google 使用关键词“VX-770”、“ivacaftor”、“VX-809”和“lumacaftor”进行搜索，获取 ivacaftor、lumacaftor 和联合治疗试验的安全性结果，并随后通过批准后评估进行报告。在 ivacaftor 和联合试验中观察到转氨酶升高。在临床前动物研究以及服用依伐卡托和联合治疗的儿童中观察到非先天性白内障。一些服用 lumacaftor 和联合治疗的患者会出现呼吸困难，通常无需停止治疗即可缓解。 Lumacaftor 是 CYP3A 的强诱导剂，而 ivacaftor 是 CYP3A 敏感的底物。联合治疗可以减少 CYP3A 底物药物的全身暴露，从而降低治疗效果。不推荐lumacaftor-ivacaftor与敏感CYP3A底物或治疗指数窄的CYP3A底物共同给药。 Lumacaftor-ivacaftor 治疗可能与眼部和肝脏副作用有关。可以提供具体的监测建议。出现呼吸困难，尤其是在治疗开始期间。应评估接受联合治疗的患者潜在的药物相互作用。 lumacaftor-ivacaftor 的风险效益比有利于治疗。
Lumacaftor-ivacaftor is indicated for treatment of cystic fibrosis (CF) in patients homozygous for the Phe-508del cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. In clinical trials, treated patients showed improved pulmonary function, reduced pulmonary exacerbations, and other benefits. This article reviews safety of this therapy. Safety findings in ivacaftor, lumacaftor and combined therapy trials, and reported subsequently through post-approval evaluation, were accessed by PubMed and Google searches using key words “VX-770”, “ivacaftor”, “VX-809”, and “lumacaftor”. Transaminitis was seen in ivacaftor and combination trials. Non-congenital cataracts were seen in pre-clinical animal studies and in children taking ivacaftor and combined therapy. Dyspnea occurs in some patients taking lumacaftor and combined therapy and usually resolves without stopping treatment. Lumacaftor is a strong inducer of CYP3A while ivacaftor is a CYP3A sensitive substrate. Combination therapy can decrease systemic exposure of medications that are substrates of CYP3A, decreasing therapeutic effect. Co-administration of lumacaftor-ivacaftor with sensitive CYP3A substrates or CYP3A substrates with narrow therapeutic index is not recommended. Lumacaftor-ivacaftor therapy may be associated with ocular and hepatic side effects. Specific recommendations for monitoring are available. Dyspnea occurs, especially during initiation of treatment. Potential drug interactions should be evaluated in patients taking combination therapy. The risk benefit ratio of lumacaftor-ivacaftor favors therapy.
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DOI：
10.1056/nejmoa1409547
发表时间：
2015-07-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Wainwright CE;Elborn JS;Ramsey BW;Marigowda G;Huang X;Cipolli M;Colombo C;Davies JC;De Boeck K;Flume PA;Konstan MW;McColley SA;McCoy K;McKone EF;Munck A;Ratjen F;Rowe SM;Waltz D;Boyle MP;TRAFFIC Study Group;TRANSPORT Study Group
通讯作者：
TRANSPORT Study Group
影响因子：
17.1
作者：
Cholon DM;Quinney NL;Fulcher ML;Esther CR Jr;Das J;Dokholyan NV;Randell SH;Boucher RC;Gentzsch M
通讯作者：
Gentzsch M
影响因子：
10
作者：
Clancy JP;Rowe SM;Accurso FJ;Aitken ML;Amin RS;Ashlock MA;Ballmann M;Boyle MP;Bronsveld I;Campbell PW;De Boeck K;Donaldson SH;Dorkin HL;Dunitz JM;Durie PR;Jain M;Leonard A;McCoy KS;Moss RB;Pilewski JM;Rosenbluth DB;Rubenstein RC;Schechter MS;Botfield M;Ordoñez CL;Spencer-Green GT;Vernillet L;Wisseh S;Yen K;Konstan MW
通讯作者：
Konstan MW
影响因子：
5.1
作者：
Yen, Elizabeth H.;Quinton, Hebe;Borowitz, Drucy
通讯作者：
Borowitz, Drucy
影响因子：
3.1
作者：
McColley, Susanna A.;Schechter, Michael S.;Konstan, Michael W.
通讯作者：
Konstan, Michael W.