Therapeutic drug monitoring of voriconazole in children: experience from a tertiary care center in China [Clinical Therapeutics]

Voriconazole is a broad-spectrum triazole antifungal and the first line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients aged 2-14 years who were subjected to voriconazole trough concentrations monitoring from June 1, 2015 to December 1, 2017. A total of 138 voriconazole trough concentrations from 42 paediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35mg/liter with high inter- and intra-individual variability. Only 50.0% of children achieved the target range (1.0~5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) adjusted the dose according to trough concentrations. Children aged <6,6~12 and >12 years old required median oral maintenance dose to achieve the target range of 11.1, 7.2 and 5.3 mg/kg twice daily respectively (P=0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P=0.033, 0.003). Affecting factors such as administration routes and co-administration with proton pump inhibitors (PPIs) explained 55.3% of variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

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