Itraconazole Dosing and Drug Monitoring at a Tertiary Children's Hospital

Author: 

Leong YH1, Boast A1, Cranswick N, Curtis N, Gwee A
Pediatr Infect Dis J. 2018 Mar 29.

Abstract: 

BACKGROUND: Itraconazole is a broad-spectrum antifungal agent used for prophylaxis and treatment of fungal infections in immunocompromised children. Achieving the recommended target serum itraconazole trough concentration of ≥0.5 mg/L is challenging in children due to variation in itraconazole pharmacokinetics with age. We studied itraconazole use and treatment outcomes in a tertiary children's hospital. METHODS: We did a ten-year retrospective review of medical records of children at the Royal Children's Hospital Melbourne who received oral itraconazole and had therapeutic drug monitoring (TDM). RESULTS: Overall, 81 children received 92 courses of oral itraconazole and had TDM. Of 222 TDM samples, 183 (82.4%) were taken at the appropriate time (trough level at steady state). Patients aged ≤12 years and >12 years required median doses of 6.2 and 3.9 mg/kg/day respectively to attain target trough levels(p12 years. At least one sub-therapeutic trough concentration was reported in 63 (76.8%) courses; in only 18 (28.6%) of these was the dose adjusted. Gastrointestinal symptoms (14/92 (15.2%) courses) and hepatotoxicity (6/92 (6.5%)) were the most frequent adverse events. Neither were associated with elevated trough levels. CONCLUSIONS: The poor attainment of target levels with current recommended dosing in children aged