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Higher Weight-Based Doses Are Required to Achieve and Maintain Therapeutic Voriconazole Serum Trough Concentrations
Tracy N Zembles1, Mahua Dasgupta2, Troy J Kenkel3
1Department of Enterprise Safety (TNZ), Children's Wisconsin, Milwaukee, WI.
Insights
Pediatric patients often need higher weight-based voriconazole doses than adults to reach therapeutic levels. Achieving and maintaining these target concentrations in children frequently requires multiple dose adjustments and therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Infectious Diseases
Background:
- Children require higher weight-based voriconazole doses than adults to achieve therapeutic serum trough concentrations (1-6 mcg/mL).
- Current dosing guidelines may not be sufficient for pediatric populations.
Purpose of the Study:
- To determine the initial voriconazole dose in children.
- To assess the proportion of pediatric patients achieving target concentrations with initial dosing.
- To evaluate the necessity of therapeutic drug monitoring (TDM) and dose modifications for maintaining therapeutic voriconazole levels in children.
Main Methods:
- Retrospective study of pediatric patients (<18 years) treated with voriconazole.
- Analysis of dosing and TDM values, compared by age groups.
- Data presented as median (IQR).
Main Results:
- 50% of patients achieved target voriconazole concentrations with initial dosing.
- An additional 31% achieved target concentrations after 2-4 dose modifications.
- Doses required were 22.3 mg/kg/day for children <12 years and 12.0 mg/kg/day for children ≥12 years.
- 59% (age <12) and 81% (age ≥12) of repeated measurements were within the therapeutic range after initial achievement.
Conclusions:
- Therapeutic voriconazole serum trough concentrations in children necessitate higher doses than currently recommended.
- Multiple dose adjustments and TDM are crucial for achieving and maintaining therapeutic voriconazole levels in pediatric patients.
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.
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