Clinical Scorecard: Real-world Evaluation of Isavuconazole in Paediatric Cancer Patients for Invasive Fungal Disease Prophylaxis and Therapy

At a Glance

Key Highlights

• Isavuconazole used primarily as second-line azole treatment for prophylaxis and therapy of invasive fungal infections, mainly pulmonary with frequent cerebral involvement
• Dose adjustments based on therapeutic drug monitoring were frequently required, especially in younger children, to achieve target trough concentrations (2.0–4.0 mg/L)
• Isavuconazole was generally well tolerated with low rates of treatment discontinuation due to suspected toxicity despite frequent co-medication contributing to laboratory abnormalities

Guideline-Based Recommendations

Diagnosis

• Identify invasive fungal disease risk in paediatric cancer and HSCT patients
• Use clinical and microbiological data to confirm fungal infection sites, especially pulmonary and cerebral

Management

• Initiate isavuconazole at 5.4 mg/kg/day maintenance dose with loading dose of 16.2 mg/kg/day for 48 hours
• Adjust dosing guided by therapeutic drug monitoring to maintain trough concentrations between 2.0 and 4.0 mg/L
• Consider isavuconazole for patients with toxicity or subtherapeutic levels on alternative azoles, or when broad spectrum and cerebral penetration are needed

Monitoring & Follow-up

• Perform regular plasma concentration measurements (Ctrough) to guide dose adjustments
• Monitor laboratory parameters for hepatotoxicity, nephrotoxicity, and electrolyte imbalances, considering co-medications
• Assess clinical response and tolerability continuously during treatment episodes

Risks

• Potential hepatotoxicity and electrolyte disturbances, often confounded by concomitant medications
• Variability in drug exposure necessitating individualized dosing
• Possible difficulties with oral capsule intake in some patients

Patient & Prescribing Data

55 paediatric patients with haematological malignancies, including 25 post-HSCT

Median treatment duration was 76 days; isavuconazole was used mainly as second-line therapy; dose adjustments were common to achieve target exposure; treatment discontinuation was mostly due to completion or palliative care

Clinical Best Practices

• Use therapeutic drug monitoring to individualize isavuconazole dosing in paediatric patients
• Consider isavuconazole for patients with intolerance or inadequate exposure to other azoles
• Monitor for toxicity but interpret laboratory abnormalities in context of polypharmacy
• Ensure multidisciplinary coordination for managing complex antifungal therapy in paediatric oncology and HSCT settings

References

• European Society for Blood and Marrow Transplantation Annual Meeting 2025