Tolerability of isavuconazole after posaconazole toxicity in leukaemia patients

Posaconazole (PCZ) is widely used for prophylaxis or treatment of invasive fungal infections (IFIs) in leukaemia patients. However, issues with PCZ tolerability can result in treatment interruption. Isavuconazole (ISA) has a similar broad spectrum of activity to PCZ, however real-world data regarding the tolerability of ISA after PCZ toxicity are lacking. In this study, the authors describe the tolerability of ISA after PCZ toxicity in leukaemia patients. The authors retrospectively assessed tolerability of ISA after PCZ toxicity in adult leukaemia patients (March 2015 to November 2017). All patients who received > 7 days of ISA within 48 hours of PCZ discontinuation were included. Laboratory markers for liver toxicity were collected at three time points: prior to PCZ, at switch to ISA, and after ISA therapy. The authors identified 23 such patients. Increased liver function tests (LFTs) were noted in 20 patients on PCZ, while 3 patients had Grade 3/4 QTc prolongation. No patient discontinued subsequent ISA due to toxicity. Grade ¾ elevations in LFTs were decreased after changing to ISA (30% after PCZ vs. 5% after ISA). No patient had significant QTc prolongation after switching to ISA. The authors concluded that ISA was well-tolerated in patients discontinuing PCZ due to toxicity, with no patient discontinuing ISA due to toxicity.

Authors: DiPippo AJ, Rausch CR, Kontoyiannis DP. ; Full Source: Mycoses. 2018 Sep 19. doi: 10.1111/myc.12851. [Epub ahead of print]