Real-life use of isavuconazole in Spanish children and adolescents
Natalia Mendoza-Palomar1,2, Silvia Simó Nebot3,4, Laura Roig-Soria1,2
1Paediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Insights
Isavuconazole (ISA) shows promise for treating invasive fungal diseases in children, particularly when other antifungals fail. Therapeutic drug monitoring is crucial, as many pediatric patients had ISA levels outside the target range.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacology and Therapeutics
- Mycology
Background:
- Isavuconazole (ISA) is approved for invasive aspergillosis and mucormycosis in children over 1 year old.
- Prior to approval, ISA was used in pediatric patients under compassionate use programs.
- This study aims to document the clinical experience with ISA in a pediatric population.
Purpose of the Study:
- To evaluate the safety and efficacy of isavuconazole (ISA) in pediatric patients.
- To describe treatment outcomes and adverse events associated with ISA use in children.
- To assess the utility of therapeutic drug monitoring (TDM) for ISA in pediatric patients.
Main Methods:
- A retrospective, multicenter study involving 107 pediatric patients (≤18 years) treated with ISA for ≥7 days between 2018-2023.
- Data collected included patient demographics, indication for ISA, prior antifungal use, clinical outcomes, adverse events, and therapeutic drug monitoring (TDM) results.
- A therapeutic range for ISA trough concentrations (Ctrough) of 2.5-5 mg/L was utilized for analysis.
Main Results:
- Of 107 patients, 95 received ISA for treatment, primarily as second-line therapy (67%) due to toxicity from previous antifungals (42%).
- In 53 patients with proven/probable invasive fungal disease (IFD), 60% had a favorable response, while 40% died (13 due to IFD).
- Adverse events occurred in 25% of patients, with hepatotoxicity being most common (10 cases requiring discontinuation). TDM revealed 59% of Ctrough values were outside the therapeutic range.
Conclusions:
- Isavuconazole (ISA) is a safe and effective treatment option for pediatric invasive fungal diseases (IFD), especially after first-line agent failure or intolerance.
- No direct correlation between ISA trough concentrations (Ctrough) and clinical outcomes was observed in this cohort.
- The high proportion of pediatric patients with out-of-range Ctrough values highlights the importance of therapeutic drug monitoring (TDM) in this population.
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.
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