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Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events

BACKGROUND: Voriconazole is approved for treatment of invasive aspergillosis and other invasive fungal infections, but the role for therapeutic drug monitoring (TDM) is not clear. METHODS: We performed a retrospective cohort study of patients at the University of Washington Medical Center and Fred H...

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Autores principales: Chu, Helen Y, Jain, Rupali, Xie, Hu, Pottinger, Paul, Fredricks, David N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655856/
https://www.ncbi.nlm.nih.gov/pubmed/23442261
http://dx.doi.org/10.1186/1471-2334-13-105
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author Chu, Helen Y
Jain, Rupali
Xie, Hu
Pottinger, Paul
Fredricks, David N
author_facet Chu, Helen Y
Jain, Rupali
Xie, Hu
Pottinger, Paul
Fredricks, David N
author_sort Chu, Helen Y
collection PubMed
description BACKGROUND: Voriconazole is approved for treatment of invasive aspergillosis and other invasive fungal infections, but the role for therapeutic drug monitoring (TDM) is not clear. METHODS: We performed a retrospective cohort study of patients at the University of Washington Medical Center and Fred Hutchinson Cancer Research Center from 2007–2009. We compared the effect of therapeutic levels on clinical outcomes and evaluated the relationship between drug levels and adverse events. RESULTS: A total of 108 patients had voriconazole TDM performed, of whom 84 (77.8%) had a hematologic malignancy and 47 (43.5%) had undergone hematopoietic stem cell transplantation. The primary reasons for treatment were presumed pulmonary aspergillosis (n = 83, 76.8%), other invasive mould infections (n = 13, 12.0%) and candidiasis (n = 9, 8.3%). There was a high degree of variability in voriconazole drug levels among patients (r(2) = 0.01; range, <0.10 - 20 mg/L). Of the 46 patients with proven or probable invasive fungal disease, 25 (54.3%) achieved partial or complete response to therapy. There was no significant relationship between therapeutic drug levels and achievement of complete or partial response at 12 weeks (OR 0.29, 95% CI: 0.05-1.34) or radiologic response (OR 1.46, 95% CI: 0.32-7.83). Overall, 45 (41.7%) patients experienced adverse events. Voriconazole levels > 5.5 mg/L were not associated with increased incidence of encephalopathy (OR 3.08, 95% CI 0.79-11.0) or hepatotoxicity (OR 2.45, 95% CI 0.49-10.1). CONCLUSIONS: Voriconazole therapeutic drug levels were not associated with improvement in clinical outcomes among patients with proven or probable invasive fungal disease. We also did not find an association between supratherapeutic drug levels and hepatoxicity or encephalopathy. It is possible that the utility of voriconazole therapeutic drug monitoring to improve clinical efficacy or decrease adverse events may be limited to a subset of high-risk patients.
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spelling pubmed-36558562013-05-17 Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events Chu, Helen Y Jain, Rupali Xie, Hu Pottinger, Paul Fredricks, David N BMC Infect Dis Research Article BACKGROUND: Voriconazole is approved for treatment of invasive aspergillosis and other invasive fungal infections, but the role for therapeutic drug monitoring (TDM) is not clear. METHODS: We performed a retrospective cohort study of patients at the University of Washington Medical Center and Fred Hutchinson Cancer Research Center from 2007–2009. We compared the effect of therapeutic levels on clinical outcomes and evaluated the relationship between drug levels and adverse events. RESULTS: A total of 108 patients had voriconazole TDM performed, of whom 84 (77.8%) had a hematologic malignancy and 47 (43.5%) had undergone hematopoietic stem cell transplantation. The primary reasons for treatment were presumed pulmonary aspergillosis (n = 83, 76.8%), other invasive mould infections (n = 13, 12.0%) and candidiasis (n = 9, 8.3%). There was a high degree of variability in voriconazole drug levels among patients (r(2) = 0.01; range, <0.10 - 20 mg/L). Of the 46 patients with proven or probable invasive fungal disease, 25 (54.3%) achieved partial or complete response to therapy. There was no significant relationship between therapeutic drug levels and achievement of complete or partial response at 12 weeks (OR 0.29, 95% CI: 0.05-1.34) or radiologic response (OR 1.46, 95% CI: 0.32-7.83). Overall, 45 (41.7%) patients experienced adverse events. Voriconazole levels > 5.5 mg/L were not associated with increased incidence of encephalopathy (OR 3.08, 95% CI 0.79-11.0) or hepatotoxicity (OR 2.45, 95% CI 0.49-10.1). CONCLUSIONS: Voriconazole therapeutic drug levels were not associated with improvement in clinical outcomes among patients with proven or probable invasive fungal disease. We also did not find an association between supratherapeutic drug levels and hepatoxicity or encephalopathy. It is possible that the utility of voriconazole therapeutic drug monitoring to improve clinical efficacy or decrease adverse events may be limited to a subset of high-risk patients. BioMed Central 2013-02-26 /pmc/articles/PMC3655856/ /pubmed/23442261 http://dx.doi.org/10.1186/1471-2334-13-105 Text en Copyright © 2013 Chu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chu, Helen Y
Jain, Rupali
Xie, Hu
Pottinger, Paul
Fredricks, David N
Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title_full Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title_fullStr Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title_full_unstemmed Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title_short Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
title_sort voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655856/
https://www.ncbi.nlm.nih.gov/pubmed/23442261
http://dx.doi.org/10.1186/1471-2334-13-105
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