TY - JOUR
T1 - Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study
AU - van der Meer, Renske
AU - Wilms, Erik B
AU - Eggermont, Margot N
AU - Paalvast, Helena M
AU - van Luin, Matthijs
AU - van Rossen, Richard C J M
AU - Heijerman, Harry G M
N1 - Publisher Copyright:
© 2024 European Cystic Fibrosis Society
PY - 2024/5
Y1 - 2024/5
N2 - BACKGROUND: 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.METHODS: 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.RESULTS: The DDI between tacrolimus and ETI resulted in an increased exposure of tacrolimus in all subjects, the dose adjusted AUC
0-24h 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.
CONCLUSION: 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.
AB - BACKGROUND: 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.METHODS: 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.RESULTS: The DDI between tacrolimus and ETI resulted in an increased exposure of tacrolimus in all subjects, the dose adjusted AUC
0-24h 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.
CONCLUSION: 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.
KW - Cystic fibrosis
KW - Drug-drug interaction
KW - Elexacaftor/tezacaftor/ivacaftor
KW - Solid organ transplant
KW - Tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=85184236229&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2024.01.008
DO - 10.1016/j.jcf.2024.01.008
M3 - Article
C2 - 38290918
SN - 1569-1993
VL - 23
SP - 549
EP - 553
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 3
ER -