Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes.

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Serval ID
serval:BIB_0AF2ACCE09D5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes.
Journal
Clinical Infectious Diseases
Author(s)
Pascual A., Calandra T., Bolay S., Buclin T., Bille J., Marchetti O.
ISSN
1537-6591 (Electronic)
ISSN-L
1058-4838
Publication state
Published
Issued date
2008
Volume
46
Number
2
Pages
201-211
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
BACKGROUND: Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity.
METHODS: This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments.
RESULTS: A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from <or=1 mg/L (the minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) in 25% of cases to >5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels <or=1 mg/L (6 [46%] of 13 patients, including 5 patients with aspergillosis, 4 of whom were treated orally with a median dosage of 6 mg/kg per day) than in those with voriconazole levels >1 mg/L (15 [12%] of 39 patients; P=.02). Blood levels >1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels >5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels <or=5.5 mg/L presented with neurological toxicity (P=.002). Comedication with omeprazole possibly contributed to voriconazole accumulation in 4 patients. In all cases, discontinuation of therapy resulted in prompt and complete neurological recovery.
CONCLUSIONS: Voriconazole therapeutic drug monitoring improves the efficacy and safety of therapy in severely ill patients with invasive mycoses.
Keywords
Adult, Aged, Antifungal Agents/administration & dosage, Antifungal Agents/adverse effects, Aspergillosis/blood, Aspergillosis/drug therapy, Candidiasis/blood, Candidiasis/drug therapy, Chromatography, High Pressure Liquid/methods, Drug Monitoring, Female, Humans, Male, Middle Aged, Mycoses/blood, Mycoses/drug therapy, Pyrimidines/administration & dosage, Pyrimidines/adverse effects, Retrospective Studies, Triazoles/administration & dosage, Triazoles/adverse effects
Pubmed
Web of science
Open Access
Yes
Create date
12/02/2008 11:54
Last modification date
25/09/2019 7:08
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