ABSTRACT
GOAL OF WORK: During the renovation works at our institution, the incidence density for invasive aspergillosis (IA) increased from <0.5 to 0.99/1,000 inpatient days in 2001. As a direct response to this increased environmental risk, itraconazole (ITC) was administered for primary prophylaxis in pediatric cancer patients for whom a particular high risk of IA was anticipated due to prolonged severe neutropenia (>10 days), autologous stem cell transplantation, acute myeloblastic leukemia or relapsed acute lymphoblastic leukemia, or high-dose steroids >3 weeks. MATERIALS AND METHODS: In this open-label, prospective observational study, ITC was given in ITC solution or capsule. Trough concentrations were measured in plasma with high-performance liquid chromatography after at least 7 days of treatment. Doses were adjusted to target plasma trough ITC concentrations > or =0.5 mg/l. RESULTS: From 2001 to 2005, 39 pediatric cancer patients received 44 prophylactic ITC cycles; 102 trough plasma concentrations were measured after oral administration. Plasma target concentrations >0.5 mg/l were achieved with both formulations. A median dose of 8 mg kg(-1) day(-1) (3.5-16.0 mg kg(-1) day(-1)) was necessary in pediatric oncology patients. The bioavailability of the liquid formulation was significantly lower when the solution was given by a feeding tube. Adverse effects (gastrointestinal, elevated transaminases, and one hemolysis) which led to the cessation of the ITC prophylaxis were reported in 11% of all courses. No breakthrough infection was seen in this pediatric population. CONCLUSION: Oral ITC offers a feasible and inexpensive option for antifungal prophylaxis in selected pediatric cancer patients. Drug monitoring and meticulous consideration of possible interactions and adverse effects are mandatory.
