Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158

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Necessity for a significant maintenance dosage reduction of voriconazole in patients with severe liver cirrhosis (Child-Pugh class C)
Takehiro YamadaShungo ImaiYasuyuki KoshizukaYuki TazawaKeisuke KagamiNaoki TomiyamaRyosuke SugawaraAkira YamagamiTsuyoshi ShimamuraKen Iseki
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JOURNAL FREE ACCESS Advance online publication

Article ID: b18-00164

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Abstract

Therapeutic drug monitoring for voriconazole, an antifungal agent, is essential for maximizing efficacy and preventing toxicity. The aim of this study was to elucidate the optimal maintenance dose of voriconazole in patients with severe liver cirrhosis (Child-Pugh class C) by reviewing the plasma trough concentrations obtained by therapeutic drug monitoring and daily doses of voriconazole. We retrospectively evaluated 6 patients with Child-Pugh class C cirrhosis who received oral voriconazole treatment and were liver transplant recipients or were awaiting liver transplantation. We compared their voriconazole trough concentrations and daily maintenance doses to those of patients who did not have liver cirrhosis (n = 56). We found that plasma voriconazole trough concentrations in all patients with Child-Pugh class C were almost within therapeutic range, and the median plasma trough concentration at steady state was not significantly different from that of patients who did not have liver cirrhosis. In addition, the median daily maintenance dose of voriconazole was significantly lower (2.13 mg/kg/d) than that of the control patients (6.27 mg/kg/d), suggesting that trough voriconazole concentrations are elevated in Child-Pugh class C patients. Thus, we conclude that oral voriconazole maintenance doses in patients with Child-Pugh class C should be reduced to approximately one-third that of patients with normal liver function, with the follow-up dose adjusted by therapeutic drug monitoring.

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© 2018 The Pharmaceutical Society of Japan
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