Prophylactic administration of voriconazole with two different doses for invasive fungal infection in children and adolescents with acute myeloid leukemia

Abstract

Background: Pediatric patients under treatment for acute myeloid leukemia (AML) are at high risk for invasive fungal infection (IFI). We evaluated the efficacy of prophylactic administration of voriconazole (VRCZ) with two different doses. Methods: Between October 2005 and June 2011, 17 children and adolescents (aged 0–20 years) undergoing chemotherapy for AML were prophylactically administered with 5 mg/kg/d of oral VRCZ. Furthermore, 22 AML patients (aged 0–19 years) were administered 10 mg/kg/d of oral VRCZ between July 2011 and December 2014. The incidences of IFI with two different doses of VRCZ were compared. Results: Irrespective of the dosage of VRCZ, eight patients developed IFI. Of these eight patients, four belonged to the 5 mg/kg/d group and four to the 10 mg/kg/d group. Cumulative incidences of IFI at 180 days after the initiation of chemotherapy were not different between the 5 mg/kg/d and 10 mg/kg/d groups. The trough plasma VRCZ concentration in the 10 mg/kg/d group ranged from < 0.09 μg/mL to 2.17 μg/mL, with a median level of 0.27 μg/mL, and patients with the targeted trough concentration (1–4 μg/mL) comprised only 18.8% of the evaluable patients in this group, whereas the trough plasma VRCZ concentration of the evaluable patients in the 5 mg/kg/d group were all below the limit of sensitivity (< 0.09 μg/mL). Conclusion: More dose escalation is required based on this study. As VRCZ concentration is considerably influenced by genetic polymorphisms and drug–drug interactions, VRCZ should be used under therapeutic drug monitoring to keep effective drug concentrations. Keywords: acute myeloid leukemia, concentration, invasive fungal infection, prophylaxis, voriconazole