Isavuconazole shortens the QTc interval

Abstract

Background

Isavuconazole is a novel antifungal drug, approved for treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval.

Objectives

To describe changes of the QTc interval induced by isavuconazole treatment.

Patients/Methods

A total of 26 adult patients from seven hospitals were included. Patients received isavuconazole for treatment of invasive fungal infection and, in one case, for prophylaxis due to QTc prolongation under fluconazole. 12-channel electrocardiograms were performed before and during treatment.

Results

24 out of 26 patients showed shortening of QTc interval. In patients with QTc shortening, QTc during isavuconazole treatment showed a mean decrease of 7.4 ± 5.8% [(36.5 ± 38.8 ms, range 7 to 202; p=0.004), compared to pre-isavuconazole ECG. One patient with available long-term follow-up showed further decrease in QTc on day 55 and 110.

Conclusion

Apart from one case report, these are the first data outside controlled clinical trials showing QTc shortening. Knowledge about cardiac effects of isavuconazole will serve to better manage the use of concomitant medications.