Cargando…

Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression

BACKGROUND: Guatemala is a developing country in Central America with limited health resources. In order to expand successful renal transplant care to children and adolescents at the lowest possible cost, our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via in...

Descripción completa

Detalles Bibliográficos
Autores principales: Méndez, Sindy, Ramay, Brooke M, Aguilar-González, Angie, Lou-Meda, Randall
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708881/
https://www.ncbi.nlm.nih.gov/pubmed/33312896
http://dx.doi.org/10.5500/wjt.v10.i11.356
_version_ 1783617633412710400
author Méndez, Sindy
Ramay, Brooke M
Aguilar-González, Angie
Lou-Meda, Randall
author_facet Méndez, Sindy
Ramay, Brooke M
Aguilar-González, Angie
Lou-Meda, Randall
author_sort Méndez, Sindy
collection PubMed
description BACKGROUND: Guatemala is a developing country in Central America with limited health resources. In order to expand successful renal transplant care to children and adolescents at the lowest possible cost, our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4. AIM: To study the safety, efficacy and the associated cost reduction of ketoconazole in combination with tacrolimus in this pediatric population. METHODS: A retrospective chart review was carried out among the cohort of pediatric renal transplant recipients treated at the Foundation for pediatric renal patients (Fundación para el Niño Enfermo Renal - FUNDANIER), a pediatric tertiary care renal transplant center in Guatemala City, Guatemala. Patient charts were reviewed to ascertain the number of transplant recipients who were transitioned from tacrolimus based immunosuppression to combination therapy with ketoconazole and tacrolimus. Twenty-five post-transplant patients that used ketoconazole combined with tacrolimus were identified. Anthropometric, clinical and laboratory data was collected from patient charts before and after the transition. RESULTS: Of the 25 patient charts reviewed 12 (48%) patients were male and the average patient age was 13 years. Twenty-four (96%) transplants were from living donors. There was a non-significant difference between the mean tacrolimus doses six months and two months prior to ketoconazole: -0.10 ± 0.04 (95%CI: 0.007, -0.029), P = 0.23. However, the difference between the mean tacrolimus doses six months prior to ketoconazole initiation and six months after ketoconazole addition was significant: 0.06 ± 0.05 (95%CI: -0.034, -0.086) P < 0.001. All tacrolimus doses were reduced by 45% after the addition of ketoconazole. Therapeutic levels of tacrolimus ranged between 6.8-8.8 ng/mL during the study period and patients demonstrated an increase in estimated glomerular filtration rate. The combination of tacrolimus and ketoconazole resulted in a 21% reduction in cost. CONCLUSION: Patients experienced an effective dose-reduction of tacrolimus with the administration of ketoconazole. There was no relevant variations in tacrolimus serum levels, number of rejections, or significant liver toxicity. The strategy allowed a cost reduction in pediatric immunosuppressive therapy.
format Online
Article
Text
id pubmed-7708881
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Baishideng Publishing Group Inc
record_format MEDLINE/PubMed
spelling pubmed-77088812020-12-11 Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression Méndez, Sindy Ramay, Brooke M Aguilar-González, Angie Lou-Meda, Randall World J Transplant Retrospective Cohort Study BACKGROUND: Guatemala is a developing country in Central America with limited health resources. In order to expand successful renal transplant care to children and adolescents at the lowest possible cost, our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4. AIM: To study the safety, efficacy and the associated cost reduction of ketoconazole in combination with tacrolimus in this pediatric population. METHODS: A retrospective chart review was carried out among the cohort of pediatric renal transplant recipients treated at the Foundation for pediatric renal patients (Fundación para el Niño Enfermo Renal - FUNDANIER), a pediatric tertiary care renal transplant center in Guatemala City, Guatemala. Patient charts were reviewed to ascertain the number of transplant recipients who were transitioned from tacrolimus based immunosuppression to combination therapy with ketoconazole and tacrolimus. Twenty-five post-transplant patients that used ketoconazole combined with tacrolimus were identified. Anthropometric, clinical and laboratory data was collected from patient charts before and after the transition. RESULTS: Of the 25 patient charts reviewed 12 (48%) patients were male and the average patient age was 13 years. Twenty-four (96%) transplants were from living donors. There was a non-significant difference between the mean tacrolimus doses six months and two months prior to ketoconazole: -0.10 ± 0.04 (95%CI: 0.007, -0.029), P = 0.23. However, the difference between the mean tacrolimus doses six months prior to ketoconazole initiation and six months after ketoconazole addition was significant: 0.06 ± 0.05 (95%CI: -0.034, -0.086) P < 0.001. All tacrolimus doses were reduced by 45% after the addition of ketoconazole. Therapeutic levels of tacrolimus ranged between 6.8-8.8 ng/mL during the study period and patients demonstrated an increase in estimated glomerular filtration rate. The combination of tacrolimus and ketoconazole resulted in a 21% reduction in cost. CONCLUSION: Patients experienced an effective dose-reduction of tacrolimus with the administration of ketoconazole. There was no relevant variations in tacrolimus serum levels, number of rejections, or significant liver toxicity. The strategy allowed a cost reduction in pediatric immunosuppressive therapy. Baishideng Publishing Group Inc 2020-11-28 2020-11-28 /pmc/articles/PMC7708881/ /pubmed/33312896 http://dx.doi.org/10.5500/wjt.v10.i11.356 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Retrospective Cohort Study
Méndez, Sindy
Ramay, Brooke M
Aguilar-González, Angie
Lou-Meda, Randall
Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title_full Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title_fullStr Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title_full_unstemmed Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title_short Exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
title_sort exploring the safety and efficacy of adding ketoconazole to tacrolimus in pediatric renal transplant immunosuppression
topic Retrospective Cohort Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708881/
https://www.ncbi.nlm.nih.gov/pubmed/33312896
http://dx.doi.org/10.5500/wjt.v10.i11.356
work_keys_str_mv AT mendezsindy exploringthesafetyandefficacyofaddingketoconazoletotacrolimusinpediatricrenaltransplantimmunosuppression
AT ramaybrookem exploringthesafetyandefficacyofaddingketoconazoletotacrolimusinpediatricrenaltransplantimmunosuppression
AT aguilargonzalezangie exploringthesafetyandefficacyofaddingketoconazoletotacrolimusinpediatricrenaltransplantimmunosuppression
AT loumedarandall exploringthesafetyandefficacyofaddingketoconazoletotacrolimusinpediatricrenaltransplantimmunosuppression