Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Department I of Internal Medicine, German Centre for Infection Research (DZIF), University of Cologne, Cologne, Germany.
Mycoses. 2018 Apr;61(4):256-260. doi: 10.1111/myc.12731. Epub 2018 Jan 3.
Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval. The objective of the study was to describe changes in the QTc interval induced by isavuconazole treatment. A total of 26 adult patients from 7 hospitals were included. Patients received isavuconazole for the treatment of invasive fungal infection and, in 1 case, for prophylaxis due to QTc prolongation under fluconazole. Twelve-channel electrocardiograms (ECGs) were performed before and during treatment. Out of 26 patients, 24 showed shortening of QTc interval. In patients with QTc shortening, QTc during isavuconazole treatment showed a mean decrease of 7.4 ± 5.8% (36.5 ± 38.8 ms, range 7-202; P = .004), compared to pre-isavuconazole ECG. One patient with available long-term follow-up showed further decrease in QTc on days 55 and 110. Apart from 1 case report, these are the first data outside controlled clinical trials showing QTc shortening. Knowledge about cardiac effects of isavuconazole will serve to better manage the use of concomitant medications.
伊曲康唑是一种新型抗真菌药物，已获批准用于治疗成人侵袭性曲霉病和毛霉病。唑类药物作为一类药物已知会延长 QTc 间期，但临床试验表明，伊曲康唑给药可能会以剂量相关的方式导致 QTc 缩短。在此，我们评估了伊曲康唑对 QTc 间期长度的影响。本研究的目的是描述伊曲康唑治疗引起的 QTc 间期变化。共纳入 7 家医院的 26 例成年患者。患者因侵袭性真菌感染接受伊曲康唑治疗，1 例因氟康唑引起 QTc 延长而接受预防治疗。在治疗前后进行了 12 通道心电图（ECG）检查。26 例患者中，24 例出现 QTc 间期缩短。在 QTc 缩短的患者中，与基线 ECG 相比，伊曲康唑治疗期间 QTc 平均降低了 7.4±5.8%（36.5±38.8ms，范围 7-202；P=0.004）。1 例有长期随访的患者在第 55 天和第 110 天 QTc 进一步降低。除了 1 例病例报告外，这些是在对照临床试验之外首次显示 QTc 缩短的数据。关于伊曲康唑心脏作用的知识将有助于更好地管理伴随药物的使用。
