Front Pharmacol. 2026 Mar 23;17:1807350. doi: 10.3389/fphar.2026.1807350. eCollection 2026.
ABSTRACT
Isavuconazole has high oral bioavailability and a predictable pharmacokinetic profile, and is a first-line agent for invasive fungal disease in adults. In children, its use is off-label. A 14-year-old boy received oral isavuconazole (200 mg daily) for pulmonary aspergillosis after allogeneic hematopoietic stem cell transplantation. After 2 months of therapy, the steady-state trough concentration increased from 2.2 mg/L to 15.0 mg/L, well above the suggested range (2.0-5.0 mg/L). Pharmacogenetic analysis revealed a CYP3A5∗3/∗3 (poor metabolizer) genotype. The drug accumulation likely reflected a combined effect of no CYP3A5 activity, long-term therapy, and possible competition within the CYP3A4 pathway from concomitant medications. It is still unclear whether these high levels cause toxic reactions. This case highlights the need for baseline and follow up steady-state therapeutic drug levels in pediatric patients receiving off-label isavuconazole, especially during extended therapy. Monitoring may help detect supratherapeutic exposure early and guide dose adjustments to optimize the therapeutic outcomes.
PMID:41948716 | PMC:PMC13050909 | DOI:10.3389/fphar.2026.1807350
