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(p<0.001). Of children aged ≤12 years, 71.4% required doses above the recommended dose of 5 mg/kg/day to achieve therapeutic levels, compared to 17.4% of those aged >12 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 <12 years suggests higher empiric doses are needed in this age group. The poor compliance with TDM guidelines highlights the need for better education about appropriate timing of sampling and dose adjustment.