PMID- 36424314 OWN - NLM STAT- MEDLINE DCOM- 20221220 LR - 20221226 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 44 IP - 12 DP - 2022 Dec TI - Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. PG - 1604-1623 LID - S0149-2918(22)00353-8 [pii] LID - 10.1016/j.clinthera.2022.10.005 [doi] AB - PURPOSE: Voriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor metabolizers. In this therapeutic drug monitoring (TDM) guideline, recommendations were made according to ethnic group. METHODS: Five clinical questions were used. For the preparation of the guideline, the performance of TDM in multicenter studies was surveyed (study 1). We also conducted a systematic review and meta-analysis (study 2) to establish recommendations for non-Asians and Asians. FINDINGS: In study 1, 401 patients were surveyed. A risk of supratherapeutic concentrations was found in Japanese patients who adhered to the recommended dose. Target trough levels were achieved in 87% of patients with dose reductions. Although the trough level measured at the onset of adverse effects (AEs) was significantly associated with hepatotoxicity, no significant correlation was found between the initial trough level and hepatotoxicity, which indicated that hepatotoxicity was successfully prevented by the trough-guided dosing. In study 2, 22 studies (11 Asian locations and 11 non-Asian locations) were included in meta-analysis for the relationship between trough cutoff level (3, 4, 5, 5.5, and 6 microg/mL) and AEs. Significant differences were found for all cutoff levels, with the highest odds ratio for 4.0 microg/mL in Asian locations. In contrast, in non-Asian locations, no more than 1 study was available for any trough cutoff level, except for 5.5 microg/mL, at which level a significant increase in AEs was found. These findings indicate that TDM is strongly recommended to prevent AEs in Asians, and TDM is generally recommended for non-Asians to address subtherapeutic concentrations. TDM on day 3 is recommended to assess pharmacokinetic properties, including loading and maintenance doses. If the patient condition permits, delaying until day 5 is suggested for Asians because of the prolonged t((1/2)) in poor metabolizers. A trough level >/=1.0 microg/mL is strongly recommended to improve efficacy. Trough levels >/=2.0 microg/mL are suggested for invasive aspergillosis. To decrease adverse effects, trough levels <4.0 microg/mL are strongly recommended in Asians, whereas trough levels <5.5 microg/mL are generally recommended in non-Asians. Maintenance doses of 4 and 3 mg/kg twice daily are recommended in non-Asians and Asians, respectively. IMPLICATIONS: Different indications, timings, and target trough levels for TDM and different regimens are suggested for Asians and non-Asians. CI - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Takesue, Yoshio AU - Takesue Y AD - Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan; Department of Clinical Infectious Diseases, Tokoname City Hospital, Tokoname, Japan. Electronic address: takesuey@hyo-med.ac.jp. FAU - Hanai, Yuki AU - Hanai Y AD - Department of Pharmacy, Toho University Omori Medical Center, Tokyo, Japan. FAU - Oda, Kazutaka AU - Oda K AD - Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan. FAU - Hamada, Yukihiro AU - Hamada Y AD - Department of Pharmacy, Tokyo Women's Medical University Hospital, Tokyo, Japan. FAU - Ueda, Takashi AU - Ueda T AD - Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Mayumi, Toshihiko AU - Mayumi T AD - Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan. FAU - Matsumoto, Kazuaki AU - Matsumoto K AD - Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Tokyo, Japan. FAU - Fujii, Satoshi AU - Fujii S AD - Department of Pharmacy, Sapporo Medical University Hospital, Hokkaidou, Japan. FAU - Takahashi, Yoshiko AU - Takahashi Y AD - Department of Pharmacy, Hyogo College of Medicine Hospital, Nishinomiya, Japan. FAU - Miyazaki, Yoshitsugu AU - Miyazaki Y AD - Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan. FAU - Kimura, Toshimi AU - Kimura T AD - Department of Pharmacy, Juntendo University Hospital, Tokyo, Japan. CN - Japanese Antimicrobial Therapeutic Drug Monitoring Guideline Committee LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20221122 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - JFU09I87TR (Voriconazole) RN - 0 (Antifungal Agents) SB - IM MH - Humans MH - Adult MH - Voriconazole/adverse effects MH - Drug Monitoring MH - Consensus MH - East Asian People MH - Antifungal Agents/therapeutic use MH - *Drug-Related Side Effects and Adverse Reactions MH - *Chemical and Drug Induced Liver Injury/drug therapy OTO - NOTNLM OT - fungal infection OT - gene phenotype guideline OT - therapeutic drug monitoring OT - voriconazole COIS- Declaration of Interest Y. Takesue received grant support from Shionogi & Co Ltd and payment for lectures from Astellas Pharma Inc and MSD Japan. K. Matsumoto received grant support from Meiji Seika Pharma Co Ltd and Sumitomo Pharma Co Ltd and speaker honoraria from Meiji Seika Pharma Co Ltd. The authors have indicated that they have no other conflicts of interest regarding the content of this article. EDAT- 2022/11/25 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/11/24 22:14 PHST- 2022/07/03 00:00 [received] PHST- 2022/10/18 00:00 [revised] PHST- 2022/10/28 00:00 [accepted] PHST- 2022/11/25 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] PHST- 2022/11/24 22:14 [entrez] AID - S0149-2918(22)00353-8 [pii] AID - 10.1016/j.clinthera.2022.10.005 [doi] PST - ppublish SO - Clin Ther. 2022 Dec;44(12):1604-1623. doi: 10.1016/j.clinthera.2022.10.005. Epub 2022 Nov 22.