The Clinical Significance of Voriconazole Therapeutic Drug Monitoring in Children With Invasive Fungal Infections

Pediatr Hematol Oncol. 2015;32(8):557-67. doi: 10.3109/08880018.2015.1088905. Epub 2015 Nov 11.

Abstract

Voriconazole is an antifungal drug used to treat fungal infections. This was a retrospective study of 61 children with hemato-oncologic diseases or solid organ transplantation who were administered voriconazole for invasive fungal infections. Of the 61 patients, 31 (50.8%) were in the therapeutic drug monitoring (TDM) group, and 30 (49.2%) were in the non-TDM group. At 12 weeks, treatment failure rate in the non-TDM group was higher than the TDM group (78.6% versus 40.0%, p = 0.038). Drug discontinuation due to adverse events was less frequent in the TDM group than the non-TDM group (26.0% versus 92.3%, p = 0.001). Children required higher dosages to maintain drug levels within the targeted therapeutic range: an average of 8.3 mg/kg/dose in patients <12 years old and 6.9 mg/kg/dose for those ≥12 years old. Treatment failure rates were higher in patients whose voriconazole levels remained below 1.0 mg/L for more than 50% of their treatment duration than those above 1.0 mg/L (71.4% vs. 9.1% after 12 weeks, p = 0.013). Serial monitoring of voriconazole levels in children is important for improving treatment response and preventing unnecessary drug discontinuation. Higher dosages are needed in children to reach therapeutic range.

Keywords: adverse events; children; therapeutic drug monitoring; treatment response; voriconazole.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Hematologic Neoplasms
  • Humans
  • Male
  • Mycoses / blood*
  • Mycoses / drug therapy*
  • Mycoses / etiology
  • Organ Transplantation
  • Time Factors
  • Voriconazole / administration & dosage*
  • Voriconazole / adverse effects
  • Voriconazole / pharmacokinetics*

Substances

  • Voriconazole