对达比加群酯出血风险不必太过担忧

圣路易斯(MD Consult)——2012年11月2日，美国食品药品管理局(FDA)公布了一项关于使用抗凝剂Pradaxa(达比加群酯)致出血风险的调查结果。在Pradaxa获准上市后，FDA收到了许多Pradaxa新使用者发生出血事件的上市后报告。为此，FDA决定着手评估，与华法林新使用者相比，Pradaxa新使用者的消化道出血和颅内出血的实际发生率。

这项风险评估采用的是FDA警戒行动(Sentinel Initiative) Mini-Sentinel监测系统的医保补偿和管理数据。FDA警戒行动旨在提供一个积极监测的系统，采用多种来源的现有医疗保健电子数据来评估已获批药品及其他医疗产品的安全性。关于Pradaxa安全性的Mini-Sentinel评价结果显示，与新使用Pradaxa相关的出血率并未高于与新使用华法林相关的出血率，这与批准Pradaxa时依据的大规模临床试验观察结果相吻合。

FDA没有更改其关于Pradaxa的推荐意见。开具Pradaxa处方的医务人员应该仔细遵照产品说明书中规定的推荐剂量(尤其是对于伴有肾功能损害的患者)以降低出血风险。此外，还应告知患者留意出血的各种体征和症状，以及哪些情况下需要及时就医。

FDA关于这个问题的安全调查仍在进行当中，正在继续评估数据的多种来源。作为这次调查的一部分，FDA正在采用Mini Sentinel数据开展2项基于方案的额外观察性评估。此外，FDA还在继续监测相关的上市后报告以寻找剂量使用不当、药物间相互作用、其他可能导致出血事件的临床因素等证据。

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ST LOUIS (MD Consult) - On November 2, 2012, the US Food and Drug Administration (FDA) announced results of an investigation concerning bleeding risks associated with use of the anticoagulant Pradaxa (dabigatran). After the approval of Pradaxa, the FDA received a large number of post-marketing reports of bleeding among Pradaxa users. Prompted by these reports, the FDA decided to examine the actual rates of gastrointestinal bleeding and intracranial hemorrhage for new users of Pradaxa, compared with new users of warfarin.

The risk assessment was performed using insurance claims and administrative data from the FDA's Mini-Sentinel pilot of the Sentinel Initiative. The Sentinel Initiative was created to provide a system for active surveillance using pre-existing electronic healthcare data from multiple sources as a means of assessing the safety of approved drugs and other medical products. The results of the Mini-Sentinel assessment regarding the safety of Pradaxa indicate that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin, which is consistent with observations from the large clinical trial used to approve Pradaxa.

The FDA has not changed its recommendations regarding Pradaxa. Health care professionals who prescribe Pradaxa should carefully follow the dosing recommendations in the drug label (especially for patients with renal impairment) to reduce the risk of bleeding. Patients should be made aware of the signs and symptoms of bleeding, and should be instructed about concerns that require medical evaluation.

The FDA is continuing to evaluate multiple sources of data in the ongoing safety review of this issue. As part of this ongoing review, the FDA is conducting 2 additional protocol-based observational assessments using Mini Sentinel data. In addition, the FDA continues to monitor post-market reports for evidence of inappropriate dosing, use of interacting drugs, and other clinical factors that might lead to a bleeding event.