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Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were deter...

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Autores principales: Risum, Malene, Vestergaard, Mai-Britt, Weinreich, Ulla Møller, Helleberg, Marie, Vissing, Nadja Hawwa, Jørgensen, René
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145181/
https://www.ncbi.nlm.nih.gov/pubmed/33922419
http://dx.doi.org/10.3390/antibiotics10050487
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author Risum, Malene
Vestergaard, Mai-Britt
Weinreich, Ulla Møller
Helleberg, Marie
Vissing, Nadja Hawwa
Jørgensen, René
author_facet Risum, Malene
Vestergaard, Mai-Britt
Weinreich, Ulla Møller
Helleberg, Marie
Vissing, Nadja Hawwa
Jørgensen, René
author_sort Risum, Malene
collection PubMed
description Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.
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spelling pubmed-81451812021-05-26 Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole Risum, Malene Vestergaard, Mai-Britt Weinreich, Ulla Møller Helleberg, Marie Vissing, Nadja Hawwa Jørgensen, René Antibiotics (Basel) Article Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ. MDPI 2021-04-23 /pmc/articles/PMC8145181/ /pubmed/33922419 http://dx.doi.org/10.3390/antibiotics10050487 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Risum, Malene
Vestergaard, Mai-Britt
Weinreich, Ulla Møller
Helleberg, Marie
Vissing, Nadja Hawwa
Jørgensen, René
Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title_full Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title_fullStr Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title_full_unstemmed Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title_short Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole
title_sort therapeutic drug monitoring of isavuconazole: serum concentration variability and success rates for reaching target in comparison with voriconazole
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145181/
https://www.ncbi.nlm.nih.gov/pubmed/33922419
http://dx.doi.org/10.3390/antibiotics10050487
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