PMID- 36225945 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221014 IS - 2042-0986 (Print) IS - 2042-0994 (Electronic) IS - 2042-0986 (Linking) VI - 13 DP - 2022 TI - Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases. PG - 20420986221127503 LID - 10.1177/20420986221127503 [doi] LID - 20420986221127503 AB - AIMS: The gene polymorphism of voriconazole metabolism-related liver enzyme is notable in East Asia population. It casts a significant influence on the rational use of voriconazole. We conducted this study to investigate the relationship between steady-state voriconazole trough concentration (C(trough)) and adverse effects (AEs), especially hepatotoxicity. METHODS: We conducted a real-world study in the Jinling Hospital from January 2015 to June 2020. A total of 140 patients receiving voriconazole were enrolled in this study. The determination and scoring of voriconazole-associated hepatotoxicity were performed according to the Roussel Uclaf Causality Assessment Method scoring scale and the severity of hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Elevated steady-state voriconazole C(trough) with concomitant AEs are the most common reason for dose adjustments during treatment. Compared with the group without any AEs, voriconazole C(trough) was significantly higher in the hepatotoxicity and neurotoxicity groups, and the incidence of both events showed an overall increasing trend with increasing voriconazole C(trough.) Hepatotoxicity occurred in 66.7% of patients within 7 days of the first dose of voriconazole and 94.4% within 15 days of the dose. Steady-state voriconazole C(trough) >3.61 mg/l was associated with an increased incidence of hepatotoxicity (area under the curve = 0.645, p = 0.047). Logistic regression analysis showed that timely voriconazole dose adjustment was a predictor of attenuated hepatotoxicity after adjustment for confounders, but hepatotoxicity was not associated with voriconazole C(trough) measured at a single time point. CONCLUSION: Hepatotoxicity and neurotoxicity correlate with voriconazole C(trough), and dose reduction in patients with elevated steady-state voriconazole C(trough) may prevent hepatotoxicity. In patients with early occurrence of hepatotoxicity, initial therapeutic drug monitoring (TDM) might predict the risk of hepatotoxicity. Follow-up TDM may be necessary to predict late onset hepatotoxicity. PLAIN LANGUAGE SUMMARY: Safety of voriconazole for the treatment of pulmonary fungal diseases Introduction: Several studies have suggested an association between the concentration of voriconazole in the blood and liver damage, but the evidence is weak. This study aimed to investigate relationships between voriconazole drug concentration and side effects and to analyze the factors affecting liver damage caused by voriconazole.Methods: We conducted a study at the Jinling Hospital from January 2015 to June 2020, in which a total of 140 patients were finally enrolled.Results: Voriconazole doses were adjusted in 44 patients due to abnormal voriconazole drug concentration or side effects, 32 patients reduced the dose and 8 patients increased the dose. An elevated liver enzyme level was the most common cause for dose adjustment. After the first dose adjustment, most patients achieved the target drug concentration. A total of 18 patients were determined as probable or highly probable to have drug-induced liver injury from voriconazole. Voriconazole drug concentration was significantly higher in the liver damage and nervous system damage groups as compared with the group without any side effects, and most liver damage events occurred within 14 days of the first dose. Voriconazole drug concentration >3.61 mg/l was associated with an increased incidence of liver damage.Conclusion: In this study, approximately one-third of patients with pulmonary fungal disease needed to adjust their dose after the standard dose of voriconazole treatment. The incidence of liver damage and nervous system damage showed an overall increasing trend with increasing voriconazole baseline concentrations. Initial therapeutic drug monitoring may be predictive of liver damage. Follow-up monitoring of liver enzymes may be needed. CI - (c) The Author(s), 2022. FAU - Shen, Kunlu AU - Shen K AUID- ORCID: 0000-0001-8869-9044 AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China. FAU - Gu, Yu AU - Gu Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China. FAU - Wang, Yu AU - Wang Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Lu, Yajie AU - Lu Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Ni, Yueyan AU - Ni Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China. FAU - Zhong, Huanhiuan AU - Zhong H AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Shi, Yi AU - Shi Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Su, Xin AU - Su X AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 510515, China. AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China. AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. LA - eng PT - Journal Article DEP - 20221008 PL - England TA - Ther Adv Drug Saf JT - Therapeutic advances in drug safety JID - 101549074 PMC - PMC9549188 OTO - NOTNLM OT - hepatotoxicity OT - safety OT - voriconazole OT - voriconazole trough concentration COIS- The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/10/14 06:00 MHDA- 2022/10/14 06:01 PMCR- 2022/10/08 CRDT- 2022/10/13 02:42 PHST- 2022/01/09 00:00 [received] PHST- 2022/09/04 00:00 [accepted] PHST- 2022/10/13 02:42 [entrez] PHST- 2022/10/14 06:00 [pubmed] PHST- 2022/10/14 06:01 [medline] PHST- 2022/10/08 00:00 [pmc-release] AID - 10.1177_20420986221127503 [pii] AID - 10.1177/20420986221127503 [doi] PST - epublish SO - Ther Adv Drug Saf. 2022 Oct 8;13:20420986221127503. doi: 10.1177/20420986221127503. eCollection 2022.