National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom.
Antimicrob Agents Chemother. 2020 Dec 16;65(1). doi: 10.1128/AAC.01511-20.
Isavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age ( = 0.012) and a daily dose of 200 mg versus 100 mg ( = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs ( = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma ( = 0.022) and a daily dose of 200 mg versus 100 mg ( = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.
伊曲康唑是最新的三唑类抗真菌药物，具有良好的药代动力学和安全性特征。关于免疫功能正常宿主长期使用伊曲康唑的情况了解较少。我们对慢性肺曲霉病患者的伊曲康唑治疗药物监测进行了回顾性服务评估。记录了在常规临床实践中进行的不良事件（AE）和剂量调整，并根据常见不良事件术语标准 5.0 对 AE 进行了分类。45 名患者（平均年龄 64 岁）共进行了 285 次伊曲康唑血药浓度测量（平均浓度 4.1mg/L）。共有 117 次测量（41%）是在每天 100mg 剂量而不是 200mg 的患者中进行的，所有患者的血药浓度均>1mg/L。年龄（=0.012）和每日 200mg 与 100mg 剂量（=0.02）是血药浓度>6mg/L 的独立预测因素。共记录了 25 名患者（56%）的 AE。报告 AE 的患者首次测量的平均药物浓度为 5.5±2mg/L，而未报告 AE 的患者为 4.2±1.7mg/L（=0.032）。预测 AE 的最佳截断值为 4.6mg/L（浓度-时间曲线下面积，0.710）。16 名患者（36%）因 AE 停用伊曲康唑治疗。26 名患者（58%）继续使用伊曲康唑超过 6 个月。哮喘（=0.022）和每日 200mg 与 100mg 剂量（=0.048）与 2 级或更高级别的 AE 相关。伊曲康唑的日剂量减少（100mg 与 200mg）使大量患者的药物水平达到令人满意的水平；它的耐受性更好，并能够延长治疗时间。
