Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study (2024)

van der Meer, R., Wilms, E. B., Eggermont, M. N., Paalvast, H. M., van Luin, M., van Rossen, R. C. J. M. (2024). Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study. Journal of Cystic Fibrosis, 23(3), 549-553. https://doi.org/10.1016/j.jcf.2024.01.008

van der Meer, Renske ; Wilms, Erik B ; Eggermont, Margot N et al. / Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study. In: Journal of Cystic Fibrosis. 2024 ; Vol. 23, No. 3. pp. 549-553.

@article{6bef4df017d84c1d892f247eeec1d8b3,

title = "Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study",

abstract = "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.",

keywords = "Cystic fibrosis, Elexacaftor/tezacaftor/ivacaftor, Drug-drug interaction, Tacrolimus, Solid organ transplant",

author = "{van der Meer}, Renske and Wilms, {Erik B} and Eggermont, {Margot N} and Paalvast, {Helena M} and {van Luin}, Matthijs and {van Rossen}, {Richard C J M} and Heijerman, {Harry G M}",

note = "Copyright {\textcopyright} 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.",

year = "2024",

month = may,

doi = "10.1016/j.jcf.2024.01.008",

language = "English",

volume = "23",

pages = "549--553",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier",

number = "3",

}

van der Meer, R, Wilms, EB, Eggermont, MN, Paalvast, HM, van Luin, M, van Rossen, RCJM 2024, 'Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study', Journal of Cystic Fibrosis, vol. 23, no. 3, pp. 549-553. https://doi.org/10.1016/j.jcf.2024.01.008

Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study. / van der Meer, Renske; Wilms, Erik B; Eggermont, Margot N et al.
In: Journal of Cystic Fibrosis, Vol. 23, No. 3, 05.2024, p. 549-553.

Research output: Contribution to journal › Article › Academic › peer-review

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 - Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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 - Elexacaftor/tezacaftor/ivacaftor

KW - Drug-drug interaction

KW - Tacrolimus

KW - Solid organ transplant

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 -

van der Meer R, Wilms EB, Eggermont MN, Paalvast HM, van Luin M, van Rossen RCJM et al. Elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using tacrolimus, a drug-drug interaction study. Journal of Cystic Fibrosis. 2024 May;23(3):549-553. Epub 2024 Jan 29. doi: 10.1016/j.jcf.2024.01.008