Voriconazole hepatotoxicity in severe liver dysfunction

Abstract

There are no studies regarding to these effects in patients with severe liver dysfunction.

Objectives: The aims of this study were to characterize voriconazole hepatotoxicity in patients with severe liver dysfunction and to compare it with a matched cohort treated with liposomal amphotericin B.

Methods: This is an observational study, in which adults patients treated with at least 4 doses of voriconazole were included. Patients treated with liposomal amphotericin B were used as control group.

Results: Sixty nine percent of patients treated with voriconazole showed changes in liver function tests (LFTs) during therapy. They showed elevated transaminases in 35%, cholestasis in 15% or a combination of both in 45%. According to the CTC classification, all patients with hepatotoxicity had a severe reaction. The Roussel Uclaf Causality Assessment Method score in all patients with hepatotoxicity was greater than 8. There was a correlation between initial loading dose greater than 300 mg (4.5 mg/kg) and the risk of hepatotoxicity (p < 0.001). The control group developed alterations in the LFTs in only 10.3% of patients.

Conclusion: Voriconazole should be used with caution in patients with severe liver dysfunction and following liver transplantation, with frequent monitoring of LFTs or using liposomal amphotericin B instead.