Isavuconazole as primary antifungal prophylaxis in pediatric hematological patients: a clinical and pharmacokinetic analysis.

Abstract

Invasive fungal diseases (IFDs) are a major threat in pediatric patients with hematologic malignancies (HMs) and hematopoietic stem cell transplantation (HSCT) recipients. Optimal antifungal prophylaxis (AFP) remains a clinical challenge. Isavuconazole (ISA), a broad-spectrum triazole, may offer a safer, more predictable option for AFP in this setting, but pediatric data are scarce. We retrospectively analyzed pediatric patients (≤18 years) with HM or HSCT who received isavuconazole as primary AFP from January 2021 to April 2025 at a single center. Isavuconazole dosing, therapeutic drug monitoring (TDM), safety, and breakthrough IFD incidence were systematically evaluated in a standardized stewardship framework. Isavuconazole was administered as primary antifungal prophylaxis in 21 patients (median age 9.6 years), 17 (77.3 %) after HSCT. Doses were weight-adjusted (100 or 200 mg/day) with loading over 48 h. No severe adverse events attributable to isavuconazole were reported. No breakthrough IFDs occurred during prophylaxis. Concomitant use of CYP3A4-interacting agents (e.g., ruxolitinib) was not associated with increased toxicity or isavuconazole level alterations. TDM was performed in all patients (188 total measurements); median Cmin was 3.4 mg/L. The target range (1-5 mg/L) was achieved in 95.2% of first TDMs. Dosage adjustments were needed in only 5.9% of cases, indicating consistent pharmacokinetics. In this retrospective cohort of high-risk pediatric hematology patients, isavuconazole used as primary antifungal prophylaxis showed favorable safety, consistent drug exposure, and no breakthrough IFDs. These findings support further prospective evaluation of isavuconazole in pediatric prophylactic strategies.