美国食品药品管理局(FDA)于9月20日批准将达比加群酯(一种口服直接凝血酶抑制剂)用于非瓣膜性心房纤颤患者(AF)，以降低其发生卒中和全身性血管栓塞的风险。

    RE-LY试验(评价抗凝疗法长期效果的随机研究)的结果是FDA做出以上决定的依据。RE-LY试验是一项纳入18,113例非瓣膜性AF患者(所有患者均具备至少1项以上卒中风险因素)的非劣性随机化国际研究，其主要终点是卒中和全身性血管栓塞的发病率。

    RE-LY试验对比了两种不同剂量的达比加群酯(盲法给药)和华法林(开标签给药)的疗效。结果发现，在预防卒中和全身性血管栓塞方面，150 mg的达比加群酯效果优于华法林和100 mg的达比加群酯。与华法林相比，两种剂量的达比加群酯均可降低患者出血性卒中的发病率，150 mg组还可以降低患者的心血管死亡风险。

Pradaxa, developed by the pharmaceutical company Boehringer Ingelheim, is the latest blood thinner in the market. It is being touted as a replacement for the chemical warfarin which has many side effects. This blood thinner has undergone years of intensive research and clinical tests. On March 18, 2008, the European Medicines Agency granted authorization for the marketing of this blood thinner for the treatment and prevention of thromboembolic disease. In another major breakthrough The United States Food and Drug Administration granted approval for use of Pradaxa on October 19, 2010. Pradaxa capsules contain the active ingredient dabigatran etexilate and it has been made as a safer alternative to warfarin which requires constant monitoring. It is the first new anticoagulant to be introduced to the market in the last fifty years. It has already gained approval for use in 75 counties.

Benefits

Pradaxa is an anticoagulant direct thrombin inhibitor. It is used for prevention of strokes and systemic embolism in patients with atrial fibrillation (AF). AF affects 1% of people around the world and 10% of people over the age of 80. Around three million patients afflicted with AF suffer from strokes every year as this leads to the formation of blood clots. So far, Warfarin was used to combat strokes but it has many adverse side effects. Pradaxa is a more effective drug with lesser side effects. Pradaxa successfully blocks the activity of thrombin (both free and clot-bound) which is primarily responsible for clot formation. It is also used in preventing blood clots in hip and knee surgery patients. Clinical tests have proved that this blood thinner, unlike warfarin, acts rapidly and displays quick results. Another major difference is that patients using this drug need not make any change in their diet. Clinical tests have proven that those given Pradaxa have a 34% lower risk of stroke or systemic embolism than patients given warfarin.

Side effects

Though this blood thinner has fewer side effects as compared to traditional blood thinners like warfarin it should be used only under a doctor’s guidance. There may be some side effects, and as this prescription medication is relatively new, many side effects may not be realized as of yet. Like other blood thinning drugs, Pradaxa too may cause bleeding even resulting in death but such incidents are less. The patient should consult the doctor if he or she observes unusual bruising, coughing up or vomiting blood. It can also cause stomach upset or burning, and stomach pain. People over 75 should use this drug carefully especially if they are already suffering from stomach ulcer and kidney problems. In rare cases it can also cause drug allergy. So far there is no evidence that this medicine can be safely be used on pregnant women. Conclusion Though Pradaxa has arrived like a breath of fresh air in the world of prescription blood thinners, it is not foolproof and has a few drawbacks. It is certainly far better and more effective than warfarin and may eventually replace the drug in the long run. Unlike warfarin, Pradaxa does not necessitate regular blood tests and prothrombin time monitoring, saving the patient needless trouble and not affecting the quality of his life.

Indication(s):

To reduce risk of stroke and systemic embolism in non-valvular atrial fibrillation.

Pharmacology:

By directly inhibiting thrombin, dabigatran and its active metabolites prevent the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited.

Dabigatran prolongs the aPTT, ecarin clotting time (ECT), and TT at therapeutic doses. With a dose of 150mg twice daily, the median peak aPTT is about 2x control; 12 hours after the last dose the median aPTT is 1.5x control. International normalized ratio (INR) is relatively insensitive to the activity of dabigatran. When converting a patient from dabigatran to warfarin, the INR is not likely to be useful until at least 2 days after discontinuing dabigatran.

The capsules should not be opened before administering, as this can increase the bioavailability of the drug by 75%.

Clinical Trials:

A multi-center, randomized parallel-group study compared two blinded doses of dabigatran (110mg twice daily or 150mg twice daily) with open-label warfarin (dosed to target INR of 2 to 3) in patients with non-valvular, persistent, paroxysmal, or permanent atrial fibrillation and one or more additional risk factors (previous stroke, TIA, or systemic embolism; left ventricular ejection fraction <40%; symptomatic heart failure ≥NYHA Class 2; age ≥75years; or age ≥65years with either diabetes, coronary artery disease, or hypertension). The primary objective was to determine if the study drug was non-inferior to warfarin in reducing the occurrence of a composite endpoint, stroke (ischemic and hemorrhagic) and systemic embolism. The study was designed to ensure that dabigatran preserved more than 50% of warfarin’s effect as established by previous warfarin studies in atrial fibrillation. Over 18,000 patients were randomized and followed for a median of 2 years. Compared to warfarin and dabigatran 110mg twice daily, dabigatran 150mg twice daily significantly reduced the primary composite endpoint (stroke and systemic embolism).

Legal Classification:

Rx

Adults:

Swallow whole. CrCl>30mL/min: 150mg twice daily. Renal impairment (CrCl 15–30mL/min): 75mg twice daily; CrCl<15mL/min or on dialysis: not recommended. Converting from warfarin, other anticoagulants: see literature. Take missed dose as soon as possible on same day; skip dose if it cannot be taken at least 6 hours before the next scheduled dose; do not double doses.

Children:

Not recommended.

Contraindication(s):

Active pathological bleeding.

Warnings/Precautions:

Increased risk of serious bleeding. Promptly evaluate signs/symptoms of blood loss (eg, a drop in hemoglobin and/or hematocrit or hypotension). Suspend treatment before invasive therapy or surgery, including dental procedures (see literature); restart promptly. Avoid lapses in therapy. Bleeding risk can be assessed by ecarin clotting time (ECT), or if not available, aPTT. Severe renal impairment. Elderly (>75 years). Labor & delivery. Pregnancy (Cat.C). Nursing mothers.

Interaction(s):

Antagonized by P-gp inducers (eg, rifampin); avoid. Increased dabigatran levels with P-gp inhibitors (eg, ketoconazole, amiodarone, quinidine, clopidogrel). May be potentiated by immediate-release verapamil; separate dosing by ≥1 hour. Concomitant NSAIDs, platelet inhibitors, heparin, fibrinolytic therapy: increased risk of bleeding. Switching to or from warfarin: monitor closely.

Adverse Reaction(s):

Gastritis-like symptoms (eg, GERD, esophagitis, erosive gastritis, gastric hemorrhage), bleeding (may be fatal).

How Supplied:

Caps—60

Last Updated:

11/19/2010