Analysis of voriconazole serum concentrations and safety profile in pediatric oncology patients

Background: Voriconazole (VCZ) serum drug levels (SDL) vary widely and are associated with increased mortality when they are below the therapeutic range for invasive aspergillosis (IA). Aim: To describe VCZ SDL in oncology pediatric patients in order to reach adequate concentrations for prophylaxis (>= 0.5 mg/L) and treatment (>= 1.0 y 2.0 mg/L) for IA and their relationship with toxicity. Patients and Methods: Retrospective analysis of VCZ SDL and toxicities recorded in oncology pediatric patients between February 2013 and November 2014. The daily dosage and SDLs were analyzed according to administration route: intravenous (IV) and oral (PO), type of therapy (prophylaxis and treatment) and patient age (< 12 y >= 12 years old). Results: 112 through levels from 26 patients were analyzed and the average age was 9.3 years-old. The SDL obtained from the IV route were 43.7%. There were more SDL >= 0.5 mg/L and >= 1.0 mg/L with the IV route than the PO route (p < 0.05). Patients younger than 12-years-old received a higher dosage than those >= 12 years old (median 18.6 and 9.2 mg/kg/d, respectively, p < 0.05). To reach SDL >= 0.5 mg/L with the PO route, a dosage of 200 mg every 12 hours showed the best results for all patients (80-100% SDL >= 0.5 mg/L). With an IV dosage between 14 and 20 mg/kg/day in patients >= 12-years old, 80% of the SDL were >= 1 mg/L and >= 2 mg/L. Inpatients younger than 12-year-old, dosages between 8-30 mg/kg/day showed similar results (50-63% of SDL >= 1 mg/L, and 36-40% of SDL >= 2 mg/L). Eight patients (30.8%) presented an adverse drug reaction and no relationship with the SDL was found. Conclusion:A VCZ standard dosage of 200 mg every 12 hours PO showed the best results for IA prophylaxis in all patients. Patients younger than 12-years-old would require higher dosages than the doses used in this study to attain adequate SDL for IA treatment. No relation with SDL and adverse reactions was found.