ST LOUIS (MD Consult) - On October 20, 2010, Boehringer Ingelheim Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved Pradaxa (dabigatran etexilate) for the prevention of stroke in patients with nonvalvular atrial fibrillation. Pradaxa is an oral anticoagulant.

Pradaxa's therapeutic activity results from direct thrombin inhibition. The manufacturer remarks that, in contrast with vitamin-K antagonists (eg, warfarin), the use of dabigatran etexilate provides effective, predictable, and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions. In addition, the safe use of Pradaxa does not demand the routine coagulation monitoring or dose adjustment characterized by the use of vitamin-K antagonists. Boehringer Ingelheim believes that the availability of Pradaxa will be especially important for the large group of patients who currently do not take any treatment for stroke prevention because they cannot tolerate or refuse to take warfarin, or whose conditions are not adequately controlled using other treatment.

The approval of Pradaxa was granted on the basis of findings from the Randomized Evaluation of Long term anticoagulant therapY (RE-LY) trial. RE-LY was a global, phase 3, randomized trial of 18,113 patients enrolled in more than 900 centers in 44 countries. The purpose of the study was to investigate whether the use of dabigatran etexilate (using 2 blinded doses) was as effective as well-controlled warfarin therapy (ie, using a target international normalized ratio [INR] range of 2.0-3.0) for stroke prevention. Patients in the study were followed for a median of 2 years, with a minimum of 1 year of follow-up. The results demonstrated that the use of dabigatran etexilate 150 mg significantly reduced the risk of stroke and systemic embolism by 35% beyond the reduction achieved with the use of warfarin. Reductions in life-threatening and intracranial bleeding were also appreciated in patients receiving dabigatran etexilate.

As with other approved anticoagulant medications, bleeding, including life-threatening and fatal bleeding, was among the most common adverse reactions reported by patients treated with Pradaxa. Gastrointestinal symptoms, including dyspepsia, abdominal pain, nausea, heartburn, and bloating also have been reported.

Patients in the United States who receive prescriptions for Pradaxa will be given a medication guide that informs them of the risk of serious bleeding. The drug will be available in 75-mg and 150-mg capsules. The 150-mg twice-daily dose is approved for all patients except for those with severe renal impairment. The approved dose for this subset of patients is 75 mg twice daily.

According to the manufacturer, Pradaxa has already been approved in 75 countries for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip or elective total knee arthroplasty.

圣路易斯(MD Consult)——2010年10月20日，勃林格殷格翰制药公司宣布，美国食品药品管理局(FDA)已批准其生产的凝血酶抑制剂Pradaxa(达比加群酯)在非瓣膜性房颤患者中用于预防卒中的发生。

 

本品为口服抗凝剂，通过直接抑制凝血酶而发挥治疗作用。勃林格殷格翰公司表示，与华法林等维生素K拮抗剂相比，本品具有有效、可预测且一致的抗凝作用，发生药物间相互作用的可能性低，并且不与食物发生相互作用。此外，与应用维生素K拮抗剂不同，在安全应用本品的情况下，不需常规监测凝血功能和调整剂量。勃林格殷格翰公司认为，对于当前因无法耐受或拒绝服用华法林而未采取任何卒中预防措施的大量患者及经其他治疗未能有效控制病情的患者，本品此次的获批显得非常重要。

 

本品的获批是基于RE-LY研究的结果。RE-LY是一项由44个国家900多个中心参与的全球性III期随机研究，共入选18,113例患者，旨在评价达比加群酯(采用2个盲态剂量)在卒中预防方面是否与对照良好的华法林治疗[目标国际标准化比值(INR)为2.0~3.0]同样有效。中位随访时间为2年，最少随访1年。结果显示，达比加群酯150 mg组卒中和全身性栓塞发生率显著降低35%，高于华法林组降幅。达比加群酯组危及生命的出血和颅内出血的发生率亦降低。

与其他获批的抗凝剂一样，本品最常见的不良反应为出血(包括危及生命的和致死性的出血)。 另外还有一些胃肠道症状，包括消化不良、腹痛、恶心、胃灼热和胃气胀。

在美国，在为患者开具本品时，还将为其提供一份用药指南，告知其使用本品存在严重出血的风险。本品为胶囊制剂，剂量规格分75 mg和150 mg。150 mg(2次/日)被批准用于所有患者，除了严重肾功能损害者之外。被批准用于严重肾功能损害者的剂量为75 mg(2次/日)。

勃林格殷格翰公司表示，本品已被75个国家批准用于择期全髋或择期全膝关节置换术后静脉血栓栓塞事件的一级预防。