止吐药昂丹司琼新标签反映QT间期延长风险

圣路易斯(MD Consult)——2012年6月29日，美国食品药品管理局(FDA)发布安全性通告，更新了止吐药Zofran(昂丹司琼)的标签，以反映与使用该药相关的QT间期延长风险。近期完成的临床研究的初步结果提示，单次静脉注射32 mg昂丹司琼可能对心电活动产生负面影响，导致QT间期延长。发生QT间期延长的患者可能倾向于发生尖端扭转型室性心动过速，后者是一种潜在致死性心律失常。

新信息显示，QT间期延长的发生具有剂量依赖性，尤其多见于单次静脉注射32 mg的患者。患有先天性长QT综合征、慢性心力衰竭、心动过缓的患者，以及正在使用可延长QT间期的其他药物的患者，使用昂丹司琼时发生QT间期延长的风险尤其高。在输注昂丹司琼之前必须先纠正电解质异常(如低钾血症或低镁血症)。

Zofran生产商葛兰素史克将从该药的标签上删除32 mg单次静脉注射的给药剂量。新标签将标明，有化疗诱导性恶心、呕吐的成人和儿童仍可继续使用昂丹司琼，但只能使用药物标签上推荐的小剂量，即每4 h注射0.15 mg/kg，共注射3剂，而且任何单剂不得超过16 mg。此外，修订后的药物标签还将加入来自新临床研究的信息。

关于QT间期延长的新信息并未导致昂丹司琼的推荐口服剂量被修改，也未影响昂丹司琼小剂量静脉注射预防术后恶心、呕吐的推荐剂量。

FDA仍在评估有关QT间期延长风险的数据，并且计划在获得更多信息后发布新通告。与使用昂丹司琼有关的不良反应可报告至FDA的MedWatch不良事件报告系统。

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ST LOUIS (MD Consult) - On June 29, 2012, the US Food and Drug Administration (FDA) issued a safety update regarding the risk of QT-interval prolongation with use of the antiemetic Zofran (ondansetron). Preliminary results from a recently completed clinical study suggest that a single 32-mg intravenous (IV) dose of ondansetron may adversely affect the electrical activity of the heart, leading to QT-interval prolongation. Patients experiencing QT-interval prolongation may be predisposed to Torsades de Pointes, a potentially fatal heart rhythm.

New information indicates that QT-interval prolongation occurs in a dose-dependent manner, and specifically at a single IV dose of 32 mg. Patients who may be at particular risk for QT-interval prolongation with the use of ondansentron are those with congenital long-QT syndrome, congestive heart failure, bradyarrhythmias, or patients receiving concomitant medications that prolong the QT interval. Electrolyte abnormalities (eg, hypokalemia or hypomagnesemia) should be corrected before ondansetron is infused.

GlaxoSmithKline, the manufacturer of Zofran, will remove the 32-mg single IV dose from the drug's label. The updated label will state that ondansetron can continue to be used in adults and children with chemotherapy-induced nausea and vomiting at the lower IV dose recommended in the drug label; that is, a dose of 0.15 mg/kg administered every 4 hours for 3 doses. However, no single IV dose should exceed 16 mg. In addition, information from the new clinical study will be included in the revised drug label.

The new information on QT-interval prolongation does not change any of the recommended oral dosing regimens for ondansetron. It also does not change the recommended lower dose IV dosing of ondansetron to prevent postoperative nausea and vomiting.

The FDA continues to assess data about the risk of QT-interval prolongation, and plans to issue an update when more information becomes available. Adverse reactions experienced with the use of ondansetron may be reported to the FDA's MedWatch Adverse Event Reporting Program.