Real-Life Use of Isavuconazole in Patients Intolerant to Other Azoles: Table 1.

To the Editor—Isavuconazole (ISV) is a broad-spectrum antifungal azole that recently received Food and Drug Administration approval for treatment of invasive aspergillosis, based on the results of a noninferiority trial that compared it with voriconazole [1]. ISV was also approved for the treatment of invasive mucormycosis, based on the results of an open-label trial with case-control analysis comparing it with amphotericin B [2]. As reported by Thompson et al [3], ISV is also active against Cryptococcus spp. and endemic dimorphic fungi, with efficacy comparable to standard regimens. Its favorable pharmacological and adverse effect profile makes ISV an appealing option for the treatment of invasive fungal diseases (IFDs) [4, 5]. Postregistration data are lacking regarding the safety and effectiveness of ISV when used in patients with intolerance to other antifungal azoles. We report our recent experience using ISV in this specific population. At our institution, from May 2015 to April 2016, ISV was used for the treatment of IFD in 28 patients. In 11 of these patients, ISV was used because of intolerance to either voriconazole or posaconazole. The criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [6] were used to classify proved or probable IFD. Patient characteristics, indications for treatment, and outcomes are summarized in Table 1. Most patients (73%) were male, and the median age was 52 years. Eight patients (73%) had a proved diagnosis of IFD, and 8 of the IFDs were caused by molds. The adverse effects that led to the switch to ISV were elevated transaminases in 4 patients, neurovisual toxicity in 3, cardiotoxicity in 2, drug interactions in 1, and dermal photosensitivity in 1 case. Change of therapy to ISV resulted in resolution of the adverse effects in 10 (91%) of the patients, after a median of 13 days (range, 1–43 days); 1 patient with QTc prolongation secondary to posaconazole could not be evaluated because a follow-up electrocardiogram was not available. Clinical Characteristics, Indications for Treatment, and Outcomes in Patients Who Received Isavuconazole as Alternative Therapy (N = 11) Abbreviations: IFD, invasive fungal disease; ISV, isavuconazole. a Histopathologic diagnosis; no species differentiation available. Clinical Characteristics, Indications for Treatment, and Outcomes in Patients Who Received Isavuconazole as Alternative Therapy (N = 11) Abbreviations: IFD, invasive fungal disease; ISV, isavuconazole. a Histopathologic diagnosis; no species differentiation available. ISV was used for a median duration of 12 weeks. One patient had transiently elevated transaminase levels during ISV treatment, but this adverse effect did not result in discontinuation of ISV. Three patients (27%) had a complete response to ISV therapy, and 6 (55%) had a partial response. The all-cause mortality rate was 18%. Our early clinical experience indicates that ISV is a well-tolerated and effective antifungal agent for the treatment of IFD in patients with intolerance to other broad-spectrum azoles. Potential conflict of interest. G. J. A. served as a consultant for Astellas and reports grant funding from Cubist/Merck. E. E. O. reports no potential conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.