Voriconazole Monitoring in Children with Invasive Fungal Infections

OBJECTIVES: The primary objective of this study was to determine the optimal daily dose of voriconazole required to achieve therapeutic trough concentrations in children 1 month to 18 years of age. The secondary objective was to analyze the association between voriconazole trough concentrations and clinical and microbiological outcomes, toxicity, and mortality. METHODS: This study was a retrospective chart review (October 2009 to August 2012) of pediatric oncology/bone marrow transplant patients with proven or probable invasive fungal infections treated with intravenous or oral voriconazole. Patients were excluded if they were older than 18 years of age, had no voriconazole concentrations drawn during the study period, or received voriconazole prior to the study period. RESULTS: Thirty-four patients were reviewed; 11 patients met all criteria for inclusion. There were 6 males and 5 females, with a median age of 8 years (range: 0.8–14.8) and a median weight of 27 kg (range: 9–74). Doses were adjusted to a median 6 mg/kg/dose (range: 3–8.7 mg/kg/dose) given every 8 (n = 5) to 12 (n = 6) hours; dose regimens varied greatly. All but 1 child achieved a voriconazole trough concentration above 1 mg/L; 7 children had a trough concentration above 2 mg/L. The median time to achieve a therapeutic trough concentration was 11 days (range: 6–37 days). Therapy failed for 4 of 11 patients, including 3 of the 4 youngest patients (p=0.022). Three of the 4 for whom therapy failed also had voriconazole trough concentrations less than 2 mg/L; this did not reach statistical significance. Voriconazole therapy was discontinued in 2 patients due to toxicity. CONCLUSIONS: This study confirmed that voriconazole pharmacokinetics vary greatly in pediatric oncology/bone marrow transplant patients. “Optimal” doses varied over nearly a 3-fold range. Younger patients may be at greater risk of poor outcomes and may require additional monitoring and dose adjustment.