In patients with atrial fibrillation, experts recommend aggressive treatment to reduce the risk of stroke and other thromboembolic complications. A new anticoagulant is available to aid prophylaxis. Last November, the Food and Drug Administration (FDA) approved Pradaxa® (dabigatran etexilate) for prevention of strokes and blood clots in patients with nonvalvular atrial fibrillation. Manufactured by Boehringer Ingelheim Pharmaceuticals Inc., Pradaxa is made from tick saliva.

Since the 1950s, warfarin sodium (Coumadin) has been the most commonly used therapy for both prophylaxis and treatment of thromboembolic complications of atrial fibrillation. Warfarin dosing is individualized based on the patient’s prothrombin time or International Normalized Ratio response to the drug. Other factors that influence dosing are sex, age, race, weight, concomitant medications, genetic factors, and dietary intake. Patients on warfarin require frequent blood tests to ensure they’re taking the proper dosage.

Unlike warfarin, Pradaxa doesn’t require frequent blood testing or special dietary considerations. It has a rapid onset and a short half-life. During initiation, Pradaxa therapy aids more rapid achievement of therapeutic drug levels and relies less on patient compliance for blood-test monitoring. The RE-LY trial of 18,113 patients, which compared the safety and effectiveness of Coumadin and Pradaxa, found patients taking Pradaxa had fewer strokes than those taking Coumadin. Further clinical trials are in progress to investigate safe use of Pradaxa for other anticoagulation needs.

How does the drug work?

The active ingredient in Pradaxa is dabigatran etexilate mesylate. Dabigatran is the first in a new class of drugs called oral direct factor Xa (FXa) inhibitors, which have a direct thrombin inhibitor effect on the complicated blood-clotting process. Thrombin, a central component in the process, induces conversion of fibrinogen into fibrin; in turn, fibrin binds platelets together to form blood clots. Pradaxa binds to thrombin and blocks its action, halting blood-clot formation.

Who should receive it?

The FDA has approved Pradaxa to prevent systemic thrombus formation and strokes in patients with non-valvular atrial fibrillation.

How is it administered?

Pradaxa is given orally in capsule form. For patients with normal renal function (creatinine clearance [CrCl] greater than 30 mL/minute), the dosage is 150 mg twice daily. The drug is contraindicated in patients with CrCl below 15 mL/minute. Specific dosing adjustments are required for safe administration.

Pradaxa can be taken with or without food. Patients should swallow the capsule whole without crushing it. Discontinuing Pradaxa can lead to an increased risk of stroke. If heparin therapy will be initiated, it should be delayed until 24 hours after the last Pradaxa dose.

What are its benefits?

In the RE-LY study, Pradaxa was shown to be more effective than warfarin in preventing strokes and blood clots. Its dosing is simpler and more straightforward than that of warfarin, with no need for frequent blood tests or consideration of weight. Pradaxa interacts with only a few other drugs and no foods. Unlike with warfarin, patients using Pradaxa can eat green, leafy vegetables and other vitamin K–enriched foods without worry. Also, the drug begins working rapidly and doesn’t require longer hospital stays to reach therapeutic anticoagulant levels. (See Comparing Coumadin and Pradaxa by clicking the PDF icon above.)

What are its drawbacks?

In clinical trials, Pradaxa increased the risk of stomach irritation and myocardial infarction (MI). Also, it must be taken twice daily.

Pradaxa is more expensive than warfarin. Average cost is $7 daily, compared to $.50 daily for warfarin. (Some argue this cost differential equalizes itself because Pradaxa doesn’t require blood-test monitoring.)

Pradaxa shouldn’t be given concomitantly with rifampin, quinidine, or St. John’s wort, as these agents may reduce its effectiveness and necessitate frequent monitoring. Although dosage adjustments aren’t needed for patients taking concomitant ketoconazole or other drugs in its class, those taking amiodarone, clarithromycin, or verapamil may have an increased serum Pradaxa concentration; they should take a lower Pradaxa dosage. Praxada isn’t recommended for use in combination with clopidogrel, dextran, heparins or low-molecular-weight heparins, thrombolytics, or other anticoagulants.

No antidote exists for Pradaxa. In case of extensive bleeding, fresh frozen plasma and other blood products should be given as supportive treatment.

What are common side effects?

In patients taking 150 mg twice daily, common side effects include bruising, shaving cuts with prolonged clotting time, dyspepsia, gastritis, GI ulcers, and esophagitis. Also, Pradaxa is more likely to cause GI bleeding and MI than warfarin. Patients taking concurrent nonsteroidal anti-inflammatory drugs may be at increased risk for bleeding.

What are the precautions?

Praxada should be used with caution in patients who:

• are younger than age 18 or older than age 75 and who weigh less than 50 kg (110 lb) or more than 110 kg (242 lb)
• have decreased renal function, hepatic disorders, an increased bleeding tendency, bacterial cardiac infections, or active GI ulcerative disease.

It should be used sparingly in patients who’ve had recent major surgery of the brain, spine, or eye or received recent epidural anesthesia. The drug’s safety during pregnancy or breastfeeding hasn’t been established.

What are the nursing considerations?

Be aware that Pradaxa is approved in the United States only for anticoagulation therapy in patients with non-­
val­vular atrial fibrillation. Instruct females to notify their healthcare professionals if they are pregnant or suspect pregnancy, are planning to become pregnant, or are breastfeeding. Periodically during Pradaxa therapy, assess patients for signs or symptoms of stroke or peripheral vascular disease.

Provide the following instructions to patients receiving Pradaxa:

• • Take capsules whole, with or without food, twice a day.
  • Be consistent with timing of doses, and try to take the drug every 12 hours.
  • If you miss a dose and the next scheduled dose is less than 6 hours away, skip the missed dose. If it’s more than 6 hours away, take the missed dose. Never take two doses at a time.
  • Store the drug in its original package at room temperature. Discard it 30 days after opening the bottle.
  • Know that anticoagulants increase your bleeding risk. Also, bleeding from small cuts will take longer than usual to stop.
  • Contact your healthcare professional if you experience excessive bruising, unexplained nosebleeds, bloody sputum, tarry stools, brown or red urine, or joint swelling.
  • Inform all your healthcare providers of all drugs and supplements you’re taking, and let them know if you have kidney problems, bleeding problems, stomach ulcers, or other medical problems.

Catherine P. Lovecchio is on the faculty of the nursing department at the University of Scranton in Scranton, Pennsylvania.