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Case Report: Pediatric isavuconazole supratherapeutic exposure: a case of long-term use, CYP3A5 poor metabolizer genotype and concomitant CYP3A4 medications

Year: 2026

Type: article

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.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1807350

Authors: Manman Liu, Lan Li, Chen Zhou, Changying Luo, Xiaodong Wang, Juan Wu

Institutions: Shanghai Jiao Tong University, Shanghai Children's Medical Center

Language: English

Topic: Antifungal resistance and susceptibility

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801