Abstract
Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.
Highlights
Invasive fungal infection (IFI) is an uncommon condition, occurring almost exclusively in immunosuppressed and critically ill patients
They show that variability of the drug remains high despite the 2012 updated dosing recommendations, and that voriconazole levels are influenced by severe hypoalbuminemia and elevated C-reactive protein (CRP)
It is reported that genetic polymorphisms conditioning voriconazole metabolism may differ depending on the patients’ ethnicity, and this is especially relevant in Asian patients [27,52,53,54,55]
Summary
Invasive fungal infection (IFI) is an uncommon condition, occurring almost exclusively in immunosuppressed and critically ill patients. It is associated with high morbidity and mortality, especially when caused by filamentous fungi [1,2,3,4,5,6]. Mainly in adults and in children, suggest that therapeutic drug monitoring (TDM) improves the efficacy and safety of voriconazole [1,8,15,16,17,18,19,20,21,22,23,24]. As between-subject differences in voriconazole plasma concentrations (PC) are more marked in children than in adults [25,26,27,28,29,30], monitoring of trough concentrations is important in children to ensure optimal treatment
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