Real-World Use of Isavuconazole in Pediatric Cancer Patients for Fungal Disease

Overview

This retrospective study evaluated isavuconazole use in 55 pediatric cancer patients, primarily with hematological malignancies, for prophylaxis and treatment of invasive fungal disease. The drug showed a favorable safety profile, required frequent dose adjustments guided by plasma concentrations, and was mainly used as second-line therapy.

Background

Children undergoing chemotherapy or hematological stem cell transplantation are at high risk for invasive fungal infections. Isavuconazole, a triazole antifungal recently approved for pediatric use, offers broad-spectrum activity, predictable pharmacokinetics, fewer drug interactions, and good cerebral penetration. Real-world data on its use in pediatric oncology patients remain limited. This study aimed to assess dosing, exposure, safety, and clinical use of isavuconazole in this vulnerable population.

Data Highlights

Key Findings

• Isavuconazole was administered in 66 treatment episodes among 55 pediatric patients (median age 9 years), mostly with hematological malignancies.
• Used primarily as second-line azole therapy (78.8%), for therapy (69.7%), secondary prophylaxis (40.9%), and primary prophylaxis (6.0%).
• Median treatment duration was 76 days; pulmonary infections predominated (97.7%), with cerebral involvement in 37.2%.
• Initial median maintenance dose was 5.4 mg/kg/day; dose adjustments were common, especially in younger children, to achieve target trough concentrations (2.0–4.0 mg/L).
• Median trough concentration was 3.3 mg/L with wide intra-episode variability; 60% of patients required doses above standard 5.4 mg/kg/day.
• Isavuconazole was generally well tolerated; grade 3–4 hepatotoxicity and electrolyte imbalances were frequent but likely multifactorial due to co-medications.

Clinical Implications

Isavuconazole is a viable antifungal option in pediatric oncology patients, especially when other azoles are ineffective, toxic, or have problematic drug interactions. Therapeutic drug monitoring is essential to optimize dosing, particularly in younger children, to achieve effective plasma concentrations. Clinicians should monitor liver function and electrolytes closely due to frequent co-medication effects.

Conclusion

Real-world data support isavuconazole as a safe and effective antifungal in pediatric cancer patients, with frequent dose adjustments guided by plasma levels to ensure adequate exposure. Its favorable profile makes it a valuable alternative when other azoles are unsuitable.

References

1. Nijhuis et al. 2025 -- Real-world evaluation of isavuconazole in paediatric patients with cancer as prophylaxis and therapy for invasive fungal disease