Necessity for a Significant Maintenance Dosage Reduction of Voriconazole in Patients with Severe Liver Cirrhosis (Child–Pugh Class C)

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  • Yamada Takehiro
    Department of Pharmacy, Hokkaido University Hospital
  • Imai Shungo
    Department of Pharmacy, Hokkaido University Hospital
  • Koshizuka Yasuyuki
    Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine
  • Tazawa Yuki
    Department of Pharmacy, Hokkaido University Hospital
  • Kagami Keisuke
    Department of Pharmacy, Hokkaido University Hospital
  • Tomiyama Naoki
    Department of Pharmacy, Hokkaido University Hospital
  • Sugawara Ryosuke
    Department of Pharmacy, Hokkaido University Hospital
  • Yamagami Akira
    Department of Pharmacy, Hokkaido University Hospital
  • Shimamura Tsuyoshi
    Division of Organ Transplantation, Hokkaido University Hospital
  • Iseki Ken
    Department of Pharmacy, Hokkaido University Hospital Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Laboratory of Clinical Pharmaceutics and Therapeutics

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Abstract

<p>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.</p>

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