Isavuconazole: A Review in Invasive Aspergillosis and Mucormycosis

Isavuconazole is a second-generation triazole with activity against a broad spectrum of clinically important fungi. Its water-soluble prodrug, isavuconazonium sulfate (Cresemba^®), available in interchangeable intravenous and oral formulations, is approved in the USA and EU for the treatment of adults with invasive aspergillosis and mucormycosis. In international phase III clinical trials, isavuconazole was efficacious and generally well tolerated in the treatment of these life-threatening diseases. In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for the primary treatment of invasive mould disease (primarily aspergillosis) and was associated with fewer drug-related treatment-emergent adverse events (TEAEs) than voriconazole. In addition, the single-arm, phase III VITAL trial and a matched case-control analysis of isavuconazole- versus amphotericin B-treated patients provided evidence of the efficacy of isavuconazole in the treatment of mucormycosis. The most commonly reported TEAEs among isavuconazole recipients were gastrointestinal disorders such as nausea, vomiting and diarrhoea. Isavuconazole has several other attributes that make it a useful new treatment option for these invasive mould diseases, including predictable pharmacokinetics, excellent bioavailability, no food effect with the oral formulation, and its potential utility in renally impaired patients given the absence of cyclodextrin in the intravenous formulation.