High frequency of isavuconazole use over voriconazole for chronic pulmonary aspergillosis: a retrospective observational study on tolerability and therapeutic drug monitoring

Abstract

ABSTRACT Chronic pulmonary aspergillosis (CPA) is a progressive fungal infection associated with significant morbidity and mortality. Voriconazole, a standard first-line treatment, is limited by poor tolerability, unpredictable pharmacokinetics, and extensive drug-drug interactions. Isavuconazole, a newer triazole with a more favorable safety profile, is currently recommended only as later-line therapy due to limited evidence in CPA. To evaluate the rate of switch from voriconazole to isavuconazole, and to assess the tolerability, pharmacokinetic profile, and drug costs of isavuconazole in a real-world CPA cohort. Single-center retrospective observational study of 40 patients with CPA enrolled at Luigi Sacco University Hospital, Milan, between October 2020 and October 2024, with therapeutic drug monitoring (TDM) throughout treatment. Of 26 patients initiated on voriconazole, 53.8% required a switch to isavuconazole, primarily due to failure to achieve therapeutic plasma concentrations (71.4%) and adverse events. Overall, 70% (28/40) of the cohort ultimately received isavuconazole. Among 233 isavuconazole TDM measurements, 17.6% fell outside the therapeutic range (1–5 mg/L), and 50% of patients required at least one dose adjustment. No patient discontinued isavuconazole due to adverse events, and no treatment failure or relapse occurred among isavuconazole-treated patients. TDM-guided dose reduction to 100 mg daily in 39.3% of patients yielded an estimated drug cost saving of 21.9%. Isavuconazole demonstrated a favorable tolerability profile with no treatment discontinuations due to adverse events. Proactive TDM proved clinically valuable in guiding dose optimization and reducing drug costs, supporting isavuconazole as a viable alternative for long-term CPA management.