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Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections

Authors Falci DR, Pasqualotto AC

Received 10 July 2013

Accepted for publication 14 August 2013

Published 22 October 2013 Volume 2013:6 Pages 163—174


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Diego R Falci,1,2 Alessandro C Pasqualotto2,3

1Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil; 2Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; 3Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil

Abstract: The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium.

Keywords: isavuconazole, invasive fungal infections, antifungals, triazoles, Aspergillus

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