Analysis of routine dose adjustments' of voriconazole in invasive fungal infections.

Mr. Korostelev, S. Coudun, E. Guiller, K. Bihan, N. Tissot, H. Junot, N. Zahr


Background:   Voriconazole is a major antifungal drug with activity contre endemic fungi, Candida and Aspergillus species inimmunocompromised patients. It presents significant neuroprotective and hepatotoxicities.Some sudies Showed a relationship entre trough concentrations of voriconazole and efficacy or toxicity.

The aim of this retrospective study is to evaluate-the therapeutic monitoringof voriconazole in invasive fungalinfections Realized at Pitié-Salpêtrière Hospital (Paris, France).

Methods:  For 29 months (from 01/01/2012 to 31/05/2014), 295 different patients (clinical trial Any outside) Were included in this study: 99 women and 196 men. At the time of dosing, the average age of all patients Was 57.3 ± 15 years. Seven hundred sixty-four doses of voriconazole Were Realized at residual concentration thesis on patients' plasma samples by a high performance liquid chromatography method.

Results:  The overall voriconazole concentration average is 2.7 ± 2.7mg / L. For a total of 295 patients Treated by voriconazole has majorité of patients (65%) Were dosed. Selon has consensually recommended concentrations of voriconazole (1-5.5mg / L), this study Showed That dose adjustment needed for Was Approximately 58% of patients dosed (over gold underdose). Such patients in 82 assays (73%) Were the object of a dose adjustment, a change in therapy or treatment discontinuation was contre 30 assays (27%) Without Any dose adjustment.

Conclusion:   Due to a high interindividual variability of voriconazole pharmacokinetics, therapeutic monitoring as critical Appears to Improve efficiency of the treatment by aiming the consensually recommended concentrations and toxicity to Reduce Especially liver and neurological toxicities. This study Showed That at Pitie-Salpetriere hospital, the patients nevertheless Treated for invasive fungal infections by voriconazole Were dosed in more than half cases, a significant proportion Does not benefit of a pharmacological monitoring. Yet, When the dosage prescribed Was, Was the dose adjustment done in according with voriconazole therapeutic monitoring in MOST cases. In conclusion, a systematic pharmacological monitoring Could Be a solution to optimize patient's outcome and to Reduce toxicities.


Full conference title: 

Réunion Interdisciplinaire de Chimiothérapie Anti Infectieuse
    • RICAI 34th (2014)