Department of Pulmonology and Adult CF Centre, Haga Hospital, Els Borst-Eilersplein 275, The Hague 2545 AA, The Netherlands.
Central Hospital Pharmacy (Laboratory AHZ), Charlotte Jacobslaan 70, The Hague 2545 AB, The Netherlands.
J Cyst Fibros. 2024 May;23(3):549-553. doi: 10.1016/j.jcf.2024.01.008. Epub 2024 Jan 29.
The use of elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis (pwCF) after solid organ transplantation is controversial because of potential drug-drug interactions (DDI) with tacrolimus. We aimed to improve insight into the safety and clinical benefits of co-administration of ETI and tacrolimus in liver or kidney transplanted adult pwCF.
In 5 pwCF, tacrolimus concentrations were monitored during 2 weeks before and 4 weeks after starting ETI treatment. Trough levels, area under the curve (AUC) and clinical effect of ETI were investigated. During the study (6 weeks in total) adverse events were monitored.
The DDI between tacrolimus and ETI resulted in an increased exposure of tacrolimus in all subjects, the dose adjusted AUC was 1.79 (median) times higher at the end of the study. Five dose adjustments were performed in 4 subjects in order to attain tacrolimus target range. No adverse events were reported and all subjects showed clinical improvement during ETI treatment.
The clinical value of ETI treatment in kidney and liver transplanted pwCF is clear. The use of ETI may increase tacrolimus levels moderately. Therefore, we recommend close monitoring of tacrolimus trough levels in patients who start ETI.
由于潜在的药物相互作用（DDI）与他克莫司，在实体器官移植后囊性纤维化（pwCF）患者中使用依利卡福特/tezacaftor/ivacaftor（ETI）存在争议。我们旨在提高对共同管理 ETI 和他克莫司在肝或肾移植成人 pwCF 中的安全性和临床益处的认识。
在开始 ETI 治疗前的 2 周和 4 周内，监测 5 名 pwCF 中的他克莫司浓度。研究了 ETI 的谷浓度、曲线下面积（AUC）和临床效果。在研究期间（总共 6 周）监测不良事件。
ETI 和他克莫司之间的 DDI 导致所有受试者他克莫司暴露增加，研究结束时剂量调整后的 AUC 高 1.79（中位数）倍。为了达到他克莫司靶标范围，4 名受试者中的 5 名进行了剂量调整。未报告不良事件，所有受试者在 ETI 治疗期间均显示出临床改善。
ETI 治疗在肾和肝移植 pwCF 中的临床价值是明确的。ETI 的使用可能会适度增加他克莫司的水平。因此，我们建议在开始 ETI 治疗的患者中密切监测他克莫司谷浓度。
