Voriconazole plasma concentrations and dosing in paediatric patients below 24 months of age.
drug monitoring
mycoses
pediatrics
prophylaxis
treatment
voriconazole
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
11
07
2023
received:
05
05
2023
accepted:
28
07
2023
medline:
4
10
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
Voriconazole (VCZ) is an important first-line option for management of invasive fungal diseases and approved in paediatric patients ≥24 months at distinct dosing schedules that consider different developmental stages. Information on dosing and exposures in children <24 months of age is scarce. Here we report our experience in children <24 months who received VCZ due to the lack of alternative treatment options. This retrospective analysis includes 50 distinct treatment episodes in 17 immunocompromised children aged between 3 and <24 months, who received VCZ between 2004 and 2022 as prophylaxis (14 patients; 47 episodes) or as empirical treatment (3 patients; 3 episodes) by mouth (46 episodes) or intravenously (4 episodes) based on contraindications, intolerance or lack of alternative options. Trough concentrations were measured as clinically indicated, and tolerability was assessed based on hepatic function parameters and discontinuations due to adverse events (AEs). VCZ was administered for a median duration of 10 days (range: 1-138). Intravenous doses ranged from 4.9 to 7.0 mg/kg (median: 6.5) twice daily, and oral doses from 3.8 to 29 mg/kg (median: 9.5) twice daily, respectively. The median trough concentration was 0.63 mg/L (range: 0.01-16.2; 38 samples). Only 34.2% of samples were in the recommended target range of 1-6 mg/L; 57.9% had lower and 7.9% higher trough concentrations. Hepatic function parameters analysed at baseline, during treatment and at end of treatment did not show significant changes during VCZ treatment. There was no correlation between dose and exposure or hepatic function parameters. In three episodes, VCZ was discontinued due to an AE (6%; three patients). In conclusion, this retrospective analysis reveals no signal for increased toxicity in paediatric patients <24 months of age. Empirical dosing resulted in mostly subtherapeutic exposures which emphasises the need for more systematic study of the pharmacokinetics of VCZ in this age group.
Substances chimiques
Voriconazole
JFU09I87TR
Antifungal Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
969-976Informations de copyright
© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.
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