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

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 because of variation in itraconazole pharmacokinetics with age. We studied itraconazole use and treatment outcomes in a tertiary children's hospital. Methods: We did a 10-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 <= 12 and >12 years of age required median doses of 6.2 and 3.9 mg/kg/d, respectively, to attain target trough levels (P < 0.001). Of children <= 12 years of age, 71.4% required doses above the recommended dose of 5 mg/kg/d to achieve therapeutic levels, compared with 17.4% of those >12 years of age. At least 1 subtherapeutic 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 was associated with elevated trough levels. Conclusions: The poor attainment of target levels with current recommended dosing in children