Real-life use of isavuconazole in Spanish children and adolescents

Abstract

BACKGROUND AND OBJECTIVES: Isavuconazole (ISA) has been recently approved for the treatment of invasive aspergillosis and mucormycosis in patients aged >1 year. Prior to this approval, it was used in paediatric patients under compassionate use. The objective of this study is to describe the experience with ISA use in children. PATIENTS AND METHODS: A descriptive, retrospective, multicentre study conducted in nine Spanish hospitals, including patients aged ?18 years who received ?7 days of ISA between 2018 and 2023. Therapeutic drug monitoring (TDM) was performed with pre-dose [trough concentration (Ctrough)] levels measured according to local protocols. A therapeutic range of 2.5-5 mg/L was used for analysis. RESULTS: A total of 107 patients (median age: 11 years, 56% male) were included. ISA was used as a treatment (95 patients), mostly as second-line therapy (64 patients, 67%), due to toxicity from previous antifungals (27 patients, 42%). Of 53 patients with proven/probable invasive fungal disease (IFD), 32 (60%) showed a favourable response and 21 (40%) died, 13 due to IFD. Twelve patients received ISA as prophylaxis and none developed breakthrough IFD. Overall, 27/107 (25%) patients experienced adverse effects, the most common being hepatotoxicity, with 10 requiring discontinuation. TDM was performed in 76/95 patients (80%), revealing 59% of Ctrough values outside the therapeutic range. CONCLUSIONS: ISA appears to be a safe and effective option for treating IFD in children, especially when first-line agents have failed or caused excessive toxicity. Although no correlation between Ctrough and clinical outcomes was observed, the significant proportion of patients with out-of-range Ctrough emphasizes the need for TDM in paediatrics.