Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, NY, USA.
J Clin Pharm Ther. 2021 Apr;46(2):286-294. doi: 10.1111/jcpt.13329. Epub 2020 Dec 7.
Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has led to improved clinical outcomes and an increase in lifespans of cystic fibrosis (CF) patients. As CF patients continue to live longer, they are at risk for developing adverse drug reactions associated with polypharmacy and CFTR modulators.
The authors aim to describe safety concerns of the current combination CFTR modulators, based upon a literature review, including notable safety concerns and recommendations for drug-drug interactions.
Cystic fibrosis transmembrane conductance regulator agents are generally well tolerated with low discontinuation rates when compared to placebo. Elevations in liver enzymes and drug-drug interactions are the most notable safety concerns. Additionally, lumacaftor/ivacaftor has shown more respiratory-related adverse events and drug-drug interactions compared to elexacaftor/tezacaftor/ivacaftor and tezacaftor/ivacaftor. Postmarketing studies are needed to determine long-term safety concerns.
囊性纤维化跨膜电导调节因子（CFTR）调节剂的治疗已导致囊性纤维化（CF）患者的临床结局改善和寿命延长。随着 CF 患者的寿命继续延长，他们面临与多药治疗和 CFTR 调节剂相关的药物不良反应的风险。
作者旨在根据文献综述描述当前联合 CFTR 调节剂的安全性问题，包括显著的安全性问题和药物相互作用的建议。
与安慰剂相比，CFTR 调节剂通常具有良好的耐受性，停药率较低。肝酶升高和药物相互作用是最值得关注的安全性问题。此外，与 elexacaftor/tezacaftor/ivacaftor 和 tezacaftor/ivacaftor 相比，lumacaftor/ivacaftor 显示出更多与呼吸相关的不良事件和药物相互作用。需要进行上市后研究以确定长期安全性问题。
