Evaluation of Empiric Voriconazole Dosing and Therapeutic Drug Monitoring in Hospitalized Pediatric Patients

Area of Science:

• Pediatric Infectious Diseases
• Clinical Pharmacology
• Mycology

Background:

• Invasive fungal infections (IFIs) pose significant risks in immunocompromised children.
• Current voriconazole dosing guidelines may lead to inadequate drug levels in pediatric patients.
• Optimizing voriconazole therapy is crucial for improving outcomes in pediatric IFIs.

Purpose of the Study:

• To evaluate voriconazole exposure and attainment of therapeutic trough concentrations in hospitalized pediatric patients.
• To identify age-specific dosing requirements for achieving therapeutic voriconazole levels.
• To inform potential adjustments to pediatric voriconazole dosing strategies.

Main Methods:

• Retrospective analysis of hospitalized pediatric patients receiving voriconazole.
• Inclusion of patients with at least one measured serum trough concentration.
• Summarization of patient demographics, voriconazole dosing, and trough concentrations, stratified by age groups (0-1, 2-11, 12-18 years).

Main Results:

• Of 106 patients, 49% had subtherapeutic voriconazole troughs, and 30% never reached therapeutic levels.
• Median oral daily doses for therapeutic troughs were higher in younger children: 21.6 mg/kg (0-1 yr), 17.9 mg/kg (2-11 yr), and 9.5 mg/kg (12-18 yr).
• Patients under 2 years exhibited the highest proportion of subtherapeutic troughs and dosing variability.

Conclusions:

• Achieving therapeutic voriconazole concentrations is difficult across all pediatric age groups.
• Current dosing may be insufficient, particularly for infants and young children.
• Higher initial voriconazole doses are likely required for pediatric patients, especially those under 2 years, to ensure effective treatment of invasive fungal infections.