PMID- 32510723 OWN - NLM STAT- MEDLINE DCOM- 20210409 LR - 20210409 IS - 1439-0507 (Electronic) IS - 0933-7407 (Print) IS - 0933-7407 (Linking) VI - 63 IP - 8 DP - 2020 Aug TI - 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. PG - 779-786 LID - 10.1111/myc.13129 [doi] AB - 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 (C(min) ) was 1-5 microg/mL. Receiver operating characteristic curves were used to determine C(min) cut-offs for AEs. RESULTS: A total of 401 patients were included. Among 108 patients with high initial C(min) , voriconazole was discontinued in 32 and the dose was reduced in 71. Among 44 patients with low initial C(min) , 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 C(min) 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 C(min) at the onset of AEs, and the C(min) cut-offs were 3.5 mug/mL for hepatotoxicity and 4.2 mug/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. CI - (c) 2020 The Authors. Mycoses published by Blackwell Verlag GmbH. FAU - Hamada, Yukihiro AU - Hamada Y AD - Department of Pharmacy, Tokyo Women's Medical University Hospital, Tokyo, Japan. FAU - Ueda, Takashi AU - Ueda T AUID- ORCID: 0000-0002-5176-9050 AD - Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Miyazaki, Yoshitsugu AU - Miyazaki Y AD - Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan. FAU - Nakajima, Kazuhiko AU - Nakajima K AD - Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Fukunaga, Keiko AU - Fukunaga K AD - Department of Hematology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Miyazaki, Taiga AU - Miyazaki T AD - Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan. FAU - Nakada-Motokawa, Nana AU - Nakada-Motokawa N AD - Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan. FAU - Nagao, Miki AU - Nagao M AD - Department of Infection Control and Prevention, Kyoto University Hospital, Kyoto, Japan. FAU - Kawamura, Hideki AU - Kawamura H AD - Division of Medical and Environmental Safety, Department of Infection Control and Prevention, Kagoshima University Hospital, Kagoshima, Japan. FAU - Shigemi, Akari AU - Shigemi A AD - Division of Medical and Environmental Safety, Department of Infection Control and Prevention, Kagoshima University Hospital, Kagoshima, Japan. FAU - Ebihara, Fumiya AU - Ebihara F AD - Department of Pharmacy, Tokyo Women's Medical University Hospital, Tokyo, Japan. FAU - Kimura, Toshimi AU - Kimura T AD - Department of Pharmacy, Tokyo Women's Medical University Hospital, Tokyo, Japan. FAU - Ikegame, Kazuhiro AU - Ikegame K AD - Department of Hematology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Uchino, Motoi AU - Uchino M AD - Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Ikeuchi, Hiroki AU - Ikeuchi H AD - Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Takesue, Yoshio AU - Takesue Y AD - Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan. LA - eng GR - JP18fk0108045/Japan Agency for Medical Research and Development/ PT - Journal Article PT - Multicenter Study DEP - 20200625 PL - Germany TA - Mycoses JT - Mycoses JID - 8805008 RN - 0 (Antifungal Agents) RN - JFU09I87TR (Voriconazole) SB - IM MH - Aged MH - *Antifungal Agents/administration & dosage/adverse effects/therapeutic use MH - Antimicrobial Stewardship MH - *Chemical and Drug Induced Liver Injury/diagnosis/pathology/prevention & control MH - Drug Monitoring MH - Drug-Related Side Effects and Adverse Reactions/diagnosis/pathology/prevention & control MH - Female MH - Humans MH - Male MH - Middle Aged MH - Mycoses/drug therapy MH - Retrospective Studies MH - *Voriconazole/administration & dosage/adverse effects/therapeutic use PMC - PMC7496238 OTO - NOTNLM OT - antifungal stewardship OT - hepatotoxicity OT - therapeutic drug monitoring OT - visual symptoms OT - voriconazole COIS- 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. EDAT- 2020/06/09 06:00 MHDA- 2021/04/10 06:00 PMCR- 2020/09/17 CRDT- 2020/06/09 06:00 PHST- 2020/03/17 00:00 [received] PHST- 2020/05/27 00:00 [revised] PHST- 2020/06/01 00:00 [accepted] PHST- 2020/06/09 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2020/06/09 06:00 [entrez] PHST- 2020/09/17 00:00 [pmc-release] AID - MYC13129 [pii] AID - 10.1111/myc.13129 [doi] PST - ppublish SO - Mycoses. 2020 Aug;63(8):779-786. doi: 10.1111/myc.13129. Epub 2020 Jun 25.