Clinical pharmacology and practical aspects of isavuconazole use

Abstract

The steadily increasing incidence of invasive fungal infections, influenced to some extent by the COVID-19 pandemic, caused by both yeast and molds makes it necessary to improve the antifungal therapies used. Historically, azoles have held a key position with respect to a range of clinical forms and patient populations. Isavuconazole is the newest of the currently clinically available next generation triazole antimycotics approved in 2015 for the therapy of invasive aspergillosis and invasive mucormycosis. Isavuconazole is active against a variety of yeast, mycelial and dimorphic fungi. The significant advantages of isavuconazole, primarily over voriconazole and in some cases over posaconazole, make it an attractive option for the therapy of difficult patients with invasive fungal infections. These potential advantages include the absence of QTc prolongation, more predictable pharmacokinetics, a significantly less complex drug interaction profile and good tolerability, especially compared to voriconazole, availability in oral and intravenous dosage forms. This review will discuss key aspects of the clinical pharmacology of isavuconazole with a focus on invasive aspergillosis and invasive mucormycosis, including the in vitro activity of the compound against various micromycetes, pharmacokinetic and pharmacodynamic characteristics that distinguish isavuconazole from other new triazoles. The review will also present the current positioning of the drug in clinical practice, primarily based on current versions of international clinical practice guidelines.