英文药名：XARELTO（rivaroxaban）

中文药名：利伐沙班膜衣片
药品介绍
美国FDA于2012年11月2日批准扩大Xarelto(rivaroxaban)的适用症,新增用于治疗深静脉血栓(DVT)或肺栓塞(PE)以及预防DVT和PE复发。FDA通过优先审批程序批准了Xarelto的这一新适用症。
适应证和用途
XARELTO一种因子Xa抑制剂适用于在正在膝或髋关节置换手术患者中预防深部静脉血栓形成(DVT)，后者可能导致肺栓塞(PE)。
剂量和给药方法
10mg口服，每天1次
剂型和规格
片：10mg
禁忌证
（1）对XARELTO超敏性
（2）活动性重要出血
警告和注意事项
（1）出血的风险：XARELTO可引起严重和致命性出血。及时评价失血的征象和症状。
（2）妊娠相关出血：在妊娠妇女中由于潜在的产科出血和/或紧急剖宫产慎用XARELTO。及时评价失血征象和症状。
不良反应
最常见不良反应 (>5%)是出血。
药物相互作用
（1）P-gp和强CYP3A4抑制剂联用：避免同时使用除非证明缺乏明显相互作用。
（2）P-gp和弱或中度CYP3A4抑制剂联用：避免同时使用除非在有肾受损患者权衡效益胜于出血风险。
（3）P-gp和强CYP3A4诱导剂联用：避免同时使用或考虑增加剂量。
（4）抗凝剂：避免同时使用。
（5）氯吡格雷[Clopidogrel]：避免同时使用除非权衡获益胜于出血风险。
特殊人群中使用
（1）哺乳母亲：终止药物或终止哺乳。
（2）肾受损：避免在有严重受损(CrCl <30 mL/min)患者中使用。在中度受损(CrCl 30至<50mL/min)慎用。
（3）肝受损：避免在有中度(Child-Pugh B)或严重(Child-Pugh C)肝受损患者或伴有凝血病有任何程度肝病患者中使用。

Xarelto: two new indications for oral anticoagulant
The direct oral factor Xa inhibitor, rivaroxaban (Xarelto), has been approved for two new indications.
In addition to the prevention of venous thromboembolism (VTE) following hip or knee replacement, Xarelto (rivaroxaban) is now licensed for:
•prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and one or more risk factors (including congestive heart failure, hypertension, ≥75 years of age, diabetes mellitus and prior stroke or transient ischaemic attack);
•treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT.
Stroke prevention in AF
Rivaroxaban (20mg once daily) was compared with dose-adjusted warfarin (target INR 2.5, range 2.0–3.0) in the pivotal randomised double-blind ROCKET AF study (n=14,264). The primary efficacy endpoint (a composite of stroke and systemic embolism) occurred in 188 patients taking rivaroxaban (1.7% per year) compared with 241 in the warfarin group (2.2% per year); hazard ratio (HR) 0.79 from the per-protocol analysis (95% CI, 0.66–0.96; p<0.001 for non-inferiority). Patients with renal impairment (CrCl 30–49ml/min; n=2950) were given a lower dose of rivaroxaban (15mg once daily) and in a subgroup analysis displayed a similar treatment effect to that found in the overall trial.
DVT
The open-label non-inferiority EINSTEIN DVT study (n=3449) investigated rivaroxaban in the treatment of acute symptomatic DVT. Patients were randomised to receive rivaroxaban 15mg twice daily for 3 weeks then 20mg once daily for 3, 6 or 12 months (n=1731), or subcutaneous enoxaparin plus warfarin or acenocoumarol (n=1718). Rivaroxaban was equally efficacious as the active control in reduction of recurrent VTE (36 events [2.1%] versus 51 events [3.0%], respectively; HR 0.68; 95% CI, 0.44–1.04; p<0.001 for non-inferiority).
The EINSTEIN-Extension trial (n=1197) investigated the efficacy of rivaroxaban (20mg once daily) against placebo in the prevention of VTE recurrence, following treatment for DVT or PE. Rivaroxaban displayed superior efficacy to placebo (8 events [1.3%] versus 42 [7.1%], respectively; HR 0.18; 95% CI, 0.09–0.39; p<0.001).
Safety
Rates of major and non-major clinically relevant bleeding were similar in the two arms of the ROCKET AF study, but fatal bleeding and rates of intracranial haemorrhage were less frequent with rivaroxaban. Additionally, similar rates of all-cause mortality and myocardial infarction were observed but major gastrointestinal bleeding was more common in the rivaroxaban group. In the EINSTEIN trial, similar rates of adverse events occurred in the two groups; however, in the EINSTEIN-Extension study, non-fatal major bleeding occurred in 4 patients in the rivaroxaban group but no patients in the placebo group (p=0.11).
New tablets
To support the new indications, Xarelto is now available as 15mg and 20mg tablets in addition to the existing 10mg tablets licensed for prevention of VTE following hip or knee replacement surgery.

FDA Approves XARELTO® (rivaroxaban tablets) to Help Prevent Deep Vein Thrombosis in Patients Undergoing Knee or Hip Replacement Surgery
XARELTO® is the only new oral anticoagulant with FDA approval in this indication
Raritan, NJ (July 1, 2011) /PRNewswire/ — Janssen Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved XARELTO® (rivaroxaban tablets), a novel, once-daily, oral anticoagulant for the prevention (prophylaxis) of deep vein thrombosis (DVT) which may lead to a pulmonary embolism (PE) in people undergoing knee or hip replacement surgery.
“The approval of once-daily XARELTO® tablets will provide a new option to help protect patients from developing venous blood clots following knee or hip replacement surgery,” said Louis M. Kwong, M.D., Professor of Orthopedic Surgery at Harbor-UCLA Medical Center, who was involved with the rivaroxaban clinical trials program in this indication. “XARELTO® has a proven clinical benefit over one of today’s most widely used options in preventing these potentially life-threatening blood clots, and the use of a once-daily pill may play an essential role in helping to simplify clinical practice.”
According to the American Academy of Orthopedic Surgeons, more than 800,000 Americans undergo knee or hip replacement surgery each year. These procedures are associated with an increased risk for DVT, a blood clot that forms in a deep vein, usually in the leg. If all or part of a DVT breaks off, it can travel to the lungs and become a PE, where it may impact the flow of oxygenated blood and lead to potentially life-threatening consequences.
The American College of Chest Physicians recommends the use of blood thinners (anticoagulants) immediately following major orthopedic replacement surgery and extended use post-discharge (at least 10 days for knee replacement, and up to 35 days for hip replacement) to help reduce such risks; however, full compliance with these guidelines using previously available options has not been widely observed. DVT and PE are the leading causes of re-hospitalization following joint replacement surgery.
“The use of blood thinners has been shown to safely and effectively help keep people from developing preventable blood clots,” said Alan Brownstein, Chief Executive Officer of the National Blood Clot Alliance. “The FDA approval of a new blood thinner, XARELTO®, offers a new option for patients seeking knee or hip replacement surgery, and we encourage people to discuss with their physicians the risk of blood clots and which blood thinner offers optimal protection as part of their pre-surgical consultation.”
Pivotal data from the XARELTO® Phase 3 clinical development program reflected in the approved label showed significantly greater efficacy of rivaroxaban, both in head-to-head comparison with enoxaparin and when comparing extended-duration (5 weeks) rivaroxaban with short-duration (2 weeks) enoxaparin, followed by placebo. In these trials, rivaroxaban and enoxaparin demonstrated similar safety profiles including low rates of major bleeding.
XARELTO® is approved for use at a 10 mg dose, once-daily for 35 days following hip replacement and for 12 days following knee replacement surgery. To date, XARELTO® is approved in more than 110 countries worldwide and has been successfully launched in more than 80 countries by Bayer HealthCare. Janssen Pharmaceuticals, Inc. holds marketing rights for XARELTO® in the U.S. The U.S. Bayer HealthCare sales force will support the Janssen Pharmaceuticals, Inc. sales force by detailing XARELTO® in designated hospital accounts.
“Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and XARELTO® provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home,” said Paul Chang, M.D., Vice President, Medical Affairs, Internal Medicine, Janssen Pharmaceuticals, Inc. “We’re pleased to make XARELTO® tablets available to physicians to help them better protect their patients from these highly preventable surgical complications.”
About XARELTO® (rivaroxaban tablets)
XARELTO® is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in people undergoing knee or hip replacement surgery. XARELTO® belongs to a group of medicines called anticoagulants. It works by blocking the blood clotting Factor Xa and thereby reduces the tendency of the blood to form clots.
XARELTO® is the third New Drug Application the U.S. FDA has approved from the Janssen Pharmaceutical Companies this year.
Additionally, XARELTO® is being evaluated for the prevention and treatment of a broad range of disorders in which blood clotting plays a major role. The extensive program of clinical trials evaluating rivaroxaban makes the compound the most studied oral, Factor Xa inhibitor in the world today. By the time of its completion, more than 65,000 patients will have participated in the rivaroxaban clinical development program. Rivaroxaban is being developed jointly by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. and Bayer HealthCare.
Important Safety Information
WHAT IS XARELTO®?
XARELTO®(rivaroxaban tablets) is a prescription medicine used to help prevent blood clots from forming in patients after hip or knee replacement surgery.
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®?
•You should take XARELTO® exactly as directed by your doctor
•Do not skip a dose or stop taking XARELTO® unless you are advised to do so by your doctor. Stopping may increase your risk of a blood clot
•If a dose is missed, take XARELTO® as soon as possible and continue on the following day, taking XARELTO® as directed by your doctor. Do not take two doses at the same time
•XARELTO® can cause bleeding, which can sometimes be serious, even life-threatening. You may find you bruise or bleed more easily while you take it. It might take longer than usual to stop bleeding
•Alert your doctor right away if you develop any:
◦Tingling, numbness or muscle weakness, especially in your legs. This is particularly important if you had a procedure called spinal or epidural puncture as part of your anesthesia for your hip or knee replacement surgery
◦Unusual bleeding or bruising (bruises that develop without an injury or grow in size)
◦New bleeding (for example, nose bleeds, bleeding gums, red urine, bright red blood in your stool, coughing up or vomiting blood)
◦Bleeding that is heavier than usual (for example, from cuts or menstruation)
◦Dizziness, weakness, or tiredness, all of which could indicate a loss of blood
◦Pain, swelling, or new fluid leakage in or around the surgical incision
WHO SHOULD NOT TAKE XARELTO®?
Tell your doctor if you have:
•Unusual bleeding
•Ever had an allergic-type (hypersensitivity) reaction to XARELTO®
WHAT SHOULD I TELL MY DOCTOR BEFORE OR WHILE TAKING XARELTO®?
•Tell your doctor or dentist about all the medicines you take
◦This includes XARELTO®, any other prescription and nonprescription medicines, over-the-counter medications, and herbal supplements
•Tell your doctor if you:
◦Have a bleeding disorder or have problems with unusual bleeding
◦Have any problems with your kidneys or liver
◦Are pregnant or planning to become pregnant
◦Are breast-feeding or are planning to breast-feed
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®?
•XARELTO® may increase your chance of bleeding. This bleeding can sometimes be serious (and even life-threatening)
•In studies side effects with XARELTO® included fluid leakage from a wound, itching, pain in arms or legs, blisters, fainting, and muscle spasm.

拜耳新型口服抗凝血剂Xarelto获EC批准
2013年5月27日，欧盟委员会（EC）已批准将拜瑞妥（Xarelto，rivaroxaban，利伐沙班）以2.5mg BID剂量（2.5mg，每日2次）联合标准抗血小板疗法，用于心脏生物标志物水平升高的成人患者急性冠脉综合征（ACS）发作后动脉粥样硬化事件（心血管死亡、心肌梗死或中风）的预防。该批准，使Xarelto成为唯一获批用于心脏生物标志物水平升高患者ACS事件后保护心脏的新型口服抗凝血剂。
动脉血栓（arterial blood clots）通过血小板激活和凝血酶生成双重途径生成，可能会导致ACS事件的再次复发。标准抗血小板疗法，仅靶向于血栓形成中的血小板激活途径，Xarelto则靶向于凝血因子Xa，该蛋白是凝血酶生成的关键触发子。
Xarelto此次新适应症的获批，是基于关键性III期ATLAS ACS2-TIMI51试验的重要临床发现。该项试验在超过15500例患者中开展，研究结果表明，在那些近期经历过ACS事件的患者中，与接受标准抗血小板疗法[低剂量阿司匹林和/或噻吩吡啶类药物（氯吡格雷或噻氯匹定）]相比，将Xarelto 2.5mg BID添加至标准抗血小板疗法，能够显着降低患者心血管死亡、心肌梗死、卒中事件，达到了复合主要疗效终点。
研究中，与冠状动脉旁路移植（CABG）无相关性的心肌梗死溶栓（TIMI）大出血事件和颅内出血（ICH）事件发生率均较低，但重要的是，使用Xarelto时，未观察到致死性颅内出血（ICH）或致死性出血风险的升高。
基于ATLAS ACS 2-TIMI51的研究结果，2012年欧洲心脏病学会（ESC）指南推荐，对于正在接受阿司匹林+氯吡格雷抗血小板疗法且伴有低出血风险的ST段抬高型心肌梗死（STEMI）患者，应考虑使用Xarelto 2.5mg BID治疗。

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注：以下产品不同的国家上市价格不同，详细以在线咨询为准！
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产地国家: 西班牙
原产地英文商品名:
XARELTO FILM COATED TAB 20mg/tab  28tabs/box
原产地英文药品名:
RIVAROXABAN
中文参考商品译名:
拜瑞妥薄膜衣片 20毫克/片  28片/盒
中文参考药品译名:
利伐沙班
中文参考化合物名称:
5-氯-氮-((5S)-2-氧-3-[-4-（3-氧-4-吗啉基）苯基]-1,3-唑烷-5-基-2-噻吩-羧酰胺
生产厂家中文参考译名:
拜耳
生产厂家英文名:
Bayer
---------------------------------------------------------------
产地国家: 西班牙
原产地英文商品名:
XARELTO FILM COATED TAB 15mg/tab 28tabs/box
原产地英文药品名:
RIVAROXABAN
中文参考商品译名:
拜瑞妥薄膜衣片 15毫克/片 28片/盒
中文参考药品译名:
利伐沙班
中文参考化合物名称:
5-氯-氮-((5S)-2-氧-3-[-4-（3-氧-4-吗啉基）苯基]-1,3-唑烷-5-基-2-噻吩-羧酰胺
生产厂家中文参考译名:
拜耳
生产厂家英文名:
Bayer
---------------------------------------------------------------
产地国家: 美国
原产地英文商品名:
XARELTO FILM COATED TAB 10mg/tab 30tabs/box
原产地英文药品名:
RIVAROXABAN
中文参考商品译名:
拜瑞妥薄膜衣片 10毫克/片 30片/盒
中文参考药品译名:
利伐沙班
中文参考化合物名称:
5-氯-氮-((5S)-2-氧-3-[-4-（3-氧-4-吗啉基）苯基]-1,3-唑烷-5-基-2-噻吩-羧酰胺
生产厂家中文参考译名:
JANSSEN PHARMS
生产厂家英文名:
JANSSEN PHARMS
---------------------------------------------------------------
产地国家: 美国
原产地英文商品名:
XARELTO FILM COATED TAB 15mg/tab 30tabs/box
原产地英文药品名:
RIVAROXABAN
中文参考商品译名:
拜瑞妥薄膜衣片 15毫克/片 30片/盒
中文参考药品译名:
利伐沙班
中文参考化合物名称:
5-氯-氮-((5S)-2-氧-3-[-4-（3-氧-4-吗啉基）苯基]-1,3-唑烷-5-基-2-噻吩-羧酰胺
生产厂家中文参考译名:
JANSSEN PHARMS
生产厂家英文名:
JANSSEN PHARMS
---------------------------------------------------------------
产地国家: 德国
原产地英文商品名:
XARELTO FILM COATED TAB 20mg/tab 30tabs/box
原产地英文药品名:
RIVAROXABAN
中文参考商品译名:
拜瑞妥薄膜衣片 20毫克/片 30片/盒
中文参考药品译名:
利伐沙班
中文参考化合物名称:
5-氯-氮-((5S)-2-氧-3-[-4-（3-氧-4-吗啉基）苯基]-1,3-唑烷-5-基-2-噻吩-羧酰胺
生产厂家中文参考译名:
JANSSEN PHARMS
生产厂家英文名:
JANSSEN PHARMS