Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2020 Aug;63(8):779-786.
doi: 10.1111/myc.13129. Epub 2020 Jun 25.

Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan

Yukihiro Hamada  1 , Takashi Ueda  2 , Yoshitsugu Miyazaki  3 , Kazuhiko Nakajima  2 , Keiko Fukunaga  4 , Taiga Miyazaki  5 , Nana Nakada-Motokawa  5 , Miki Nagao  6 , Hideki Kawamura  7 , Akari Shigemi  7 , Fumiya Ebihara  1 , Toshimi Kimura  1 , Kazuhiro Ikegame  4 , Motoi Uchino  8 , Hiroki Ikeuchi  8 , Yoshio Takesue  2
Affiliations
Multicenter Study

Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan

Yukihiro Hamada et al. Mycoses. 2020 Aug.

Abstract

Background: Hepatotoxicity and visual symptoms are common adverse effects (AEs) of voriconazole therapy.

Objective: To retrospectively evaluate the effects of treatment modification based on therapeutic drug monitoring on AEs in patients undergoing voriconazole therapy.

Methods: The target voriconazole trough concentration (Cmin ) was 1-5 µg/mL. Receiver operating characteristic curves were used to determine Cmin cut-offs for AEs.

Results: A total of 401 patients were included. Among 108 patients with high initial Cmin , voriconazole was discontinued in 32 and the dose was reduced in 71. Among 44 patients with low initial Cmin , voriconazole was discontinued in 4 and the dose was increased in 19. Hepatotoxicity occurred in 6.0% of patients, after a median of 10 days. Visual symptoms were evident in 9.5% of patients after a median of 4 days. Initial Cmin was significantly associated with visual symptoms but not hepatotoxicity, which suggested the effect of treatment modification on hepatotoxicity. However, both hepatotoxicity and visual symptoms were significantly correlated with Cmin at the onset of AEs, and the Cmin cut-offs were 3.5 μg/mL for hepatotoxicity and 4.2 μg/mL for visual symptoms. Voriconazole was discontinued after the occurrence of AEs in 62.5% of patients with hepatotoxicity but only 26.3% of patients with visual symptoms. With dose adjustment, treatment was completed in 8/9 patients with hepatotoxicity and 27/28 patients with visual symptoms.

Conclusions: A significant preventive effect was demonstrated on hepatotoxicity, but not on visual symptoms because of earlier occurrence. With treatment modification after the occurrence of AEs, most patients completed therapy.

Keywords: antifungal stewardship; hepatotoxicity; therapeutic drug monitoring; visual symptoms; voriconazole.

PubMed Disclaimer

Conflict of interest statement

Y. Takesue has received grant support from Sumitomo Dainippon Pharma Co., Ltd., and Shionogi & Co., Ltd., and payment for lectures from Astellas Pharma Inc, and MSD Japan. T. Miyazaki has received grants from Pfizer and MSD and lectures honoraria from Pfizer, MSD, Sumitomo Dainippon Pharma and Astellas Pharma. Y. Miyazaki has received payment for lectures from Astellas Pharma Inc, Sumitomo Dainippon Pharma Co. Ltd. and MSD Japan. Other authors have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Receiver operating characteristic curve of initial trough concentration (C min) and C min at the occurrence of adverse effects to predict adverse effects
See this image and copyright information in PMC

References

    1. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327‐360. - PubMed
    1. Ullmann AJ, Akova M, Herbrecht R, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect. 2012;18(Suppl 7):53‐67. - PubMed
    1. Saito T, Fujiuchi S, Tao Y, et al. Efficacy and safety of voriconazole in the treatment of chronic pulmonary aspergillosis: experience in Japan. Infection. 2012;40:661‐667. - PubMed
    1. Luong ML, Hosseini‐Moghaddam SM, Singer LG, et al. Risk factors for voriconazole hepatotoxicity at 12 weeks in lung transplant recipients. Am J Transplant. 2012;12:1929‐1935. - PubMed
    1. Zonios DI, Gea‐Banacloche J, Childs R, et al. Hallucinations during voriconazole therapy. Clin Infect Dis. 2008;47:e7‐e10. - PMC - PubMed

Publication types

MeSH terms