Higher Weight-Based Doses Are Required to Achieve and Maintain Therapeutic Voriconazole Serum Trough Concentrations in Children

Abstract

OBJECTIVE Children require weight-based voriconazole doses proportionately larger than adults to achieve therapeutic serum trough concentrations (1–6 mcg/mL). The objective of this quality improvement project was to determine the initial dose, proportion of patients achieving target concentrations with initial dosing, and subsequent therapeutic drug monitoring and dose modifications needed to achieve and maintain therapeutic voriconazole concentrations in children. METHODS This retrospective study evaluated children aged <18 years treated with voriconazole during the study period. Dosing and therapeutic drug monitoring (TDM) values were collected and compared by age. Data are presented as median (IQR), unless otherwise stated. RESULTS Fifty-nine patients, aged 10.4 (3.7–14.7) years and 49% female, met inclusion criteria; 42 had at least 1 steady-state voriconazole serum trough concentration measured. Twenty-one of 42 (50%) achieved the target concentration at the first steady-state measurement. An additional 13 of 42 (31%) achieved the target following 2 to 4 dose modifications. The dose required to first achieve a value in the target range was 22.3 (18.0–27.1) mg/kg/day in children aged <12 years and 12.0 (9.8–14.0) mg/kg/day in children aged ≥12 years. After reaching the target, 59% and 81% of repeated steady-state measurements were in the therapeutic range in patients aged <12 years and ≥12 years, respectively. CONCLUSIONS Reaching therapeutic voriconazole serum trough concentrations required doses larger than currently recommended by the American Academy of Pediatrics. Multiple dose adjustments and TDM measurements were required to achieve and maintain therapeutic voriconazole serum concentrations.