Drug Design, Development and Therapy (Apr 2018)
Spotlight on isavuconazole in the treatment of invasive aspergillosis and mucormycosis: design, development, and place in therapy
Abstract
Jeffrey D Jenks,1,* Helmut JF Salzer,2,3,* Juergen Prattes,4,5,* Robert Krause,4,5,* Dieter Buchheidt,6,* Martin Hoenigl1,3,7,8,* 1Department of Medicine, University of California San Diego, San Diego, CA, USA; 2Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany; 3German Center for Infection Research, Clinical Tuberculosis Center, Leibniz Lung Center, Borstel, Germany; 4Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria; 5CBmed – Center for Biomarker Research in Medicine, Graz, Austria; 6Department of Hematology and Oncology, Mannheim University Hospital, Heidelberg University, Mannheim, Germany; 7Division of Pulmonology, Medical University of Graz, Graz, Austria; 8Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, CA, USA *All authors contributed equally to this work Abstract: In recent decades, important advances have been made in the diagnosis and treatment of invasive aspergillosis (IA) and mucormycosis. One of these advances has been the introduction of isavuconazole, a second-generation broad spectrum triazole with a favorable pharmacokinetic and safety profile and few drug–drug interactions. Phase III trials in patients with IA and mucormycosis demonstrated that isavuconazole has similar efficacy to voriconazole for the treatment of IA (SECURE trial) and liposomal amphotericin B for the treatment of mucormycosis (VITAL trial with subsequent case–control analysis) and a favorable safety profile with significantly fewer ocular, hepatobiliary, and skin and soft tissue adverse events compared to voriconazole. As a result, recent IA guidelines recommend isavuconazole (together with voriconazole) as gold standard treatment for IA in patients with underlying hematological malignancies. In contrast to liposomal amphotericin B, isavuconazole can be safely administered in patients with reduced renal function and is frequently used for the treatment of mucormycosis in patients with reduced renal function. Updated guidelines on mucormycosis are needed to reflect the current evidence and give guidance on the use of isavuconazole for mucormycosis. Studies are needed to evaluate the role of isavuconazole for 1) anti-mold prophylaxis in high-risk patients, 2) salvage treatment for IA and mucormycosis, and 3) treatment for other mold infections such as Scedosporium apiospermum. Keywords: TDM, plasma level, triazole, SECURE, VITAL, susceptibility, real life
