Is Halving Maintenance of Voriconazole Safe and Efficient in Patients Suffering from Invasive Fungal Infections with Serious Hepatic Dysfunction?

Background: There is a wide debate about the efficacy and safety of voriconazole in patients with impaired hepatic function at Child-Pugh C level.

Objective: The purpose of this study was to investigate the safety and efficacy between the two groups treated with different dosages of voriconazole (400mg/day vs 200mg/day) in the treatment of invasive fungal infections (IFIs) in patients with hepatic dysfunction.

Methods: A retrospective study enrolling patients with hepatic dysfunction receiving intravenous voriconazole for IFIs from January 1st, 2017, to December 30th, 2021 was conducted. Patients were enrolled in the 400mg per day dose group and 200mg per day dose group. In patients with the same degree of hepatic impairment, factors affecting prognosis were screened and differences in steady-state blood trough concentrations (C) of voriconazole, positive G/GM tests and adverse effects (AEs) were compared between the two groups described above.

Results: In total, 308 patients with IFIs were enrolled. For Child-Pugh C class, patients receiving the halved maintenance dose had a lower C and AEs rate but higher recovered rate compared to those receiving maintenance dose, and significant predictors of recovery were dosage (OR, 5.131; 95% CI, 1.599-16.464; p = 0.006) and diabetes (OR, 0.111; 95% CI, 0.020-0.597; p = 0.010). For patients of Child-Pugh A & B class, chronic liver disease (OR, 0.334; 95% CI, 0.159-0.704; p = 0.004) was a prognosis-related factor.

Conclusion: Halving maintenance dose ensure the efficacy and safety of voriconazole in patients suffering from invasive fungal infections with serious hepatic dysfunction.