Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data

The aim of this study was to investigate whether routine therapeutic drug monitoring (TDM) of voriconazole (VRCZ) reduced discontinuation due to hepatotoxicity. Hepatotoxicity was observed in 15 (51.7%) out of 29 patients. The percentages of patients who developed hepatotoxicity within 4 days and 1 week were 26.7 and 46.7%, respectively. The drug trough concentrations in patients with and without hepatotoxicity were 5.55 +/- 2.73 and 2.36 +/- 1.67 mu g/ml (P<0.01, the two-sided Student's t-test), respectively. Trough concentrations reached the target of 1-5 mu g/ml in patients with gradual dose reductions based on TDM, and, consequently, liver enzyme levels returned to the original levels before the VRCZ treatment. All patients eventually continued effective VRCZ therapy despite its hepatotoxicity. Thus, dose adjustments by TDM to achieve the target trough concentrations is useful in order to avoid hepatotoxicity and enable continued effective VRCZ therapy for Japanese patients with invasive fungal infections.