Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis
Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis
复制标题
DOI：
10.1128/aac.01511-20
复制
发表时间：
2021-01-01
影响因子：
4.9
通讯作者：
Rautemaa-Richardson, Riina
中科院分区：
文献类型：
--
作者：
Kosmidis, Chris;Otu, Akan;Rautemaa-Richardson, Riina
艾沙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。关于其在免疫活性宿主中的长期使用知之甚少。我们对慢性肺曲霉病患者艾沙康唑治疗药物监测进行了回顾性服务评价。记录常规临床实践期间的不良事件（AE）和剂量调整，并根据不良事件通用术语标准v5.0对AE进行分类。45例患者（平均年龄64岁）测定了285个艾沙康唑血药浓度（平均水平4.1 mg/L）。总共有117次（41%）测量是在每天100毫克而不是200毫克的患者身上进行的，所有人的血液水平都大于1毫克/升。年龄（P = 0.012）和每日剂量200 mg与100 mg（P = 0.02）是>6 mg/L水平的独立预测因素。25例患者（56%）记录了AE。首次测量时，报告AE的患者的平均药物水平为5.5 +/- 2 mg/L，而未报告AE的患者为4.2 +/- 1.7 mg/L（P = 0.032）。最佳预测AE的截止阈值为4.6 mg/L（浓度-时间曲线下面积，0.710）。16例患者（36%）因AE而中止艾沙康唑治疗。26例患者（58%）继续使用艾沙康唑超过6个月。哮喘（P = 0.022）和每日剂量200 mg与100 mg（P = 0.048）与2级或以上AE相关。减少艾沙康唑的日剂量（100 mg vs 200 mg）可在大量患者中获得满意的药物水平;其耐受性更好，并可延长治疗时间。
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 (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 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 (P = 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 (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 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.