Brand Name(s):

• Pradaxa®

IMPORTANT WARNING:

[Posted 12/19/2012]ISSUE:The U.S. Food and Drug Administration (FDA) is informing health care professionals and the public that the blood thinner (anticoagulant) dabigatran etexilate mesylate (Pradaxa) should not be used to prevent stroke or blood clots (major thromboembolic events) in patients with mechanical heart valves, also known as mechanical prosthetic heart valves. A clinical trial in Europe (the RE-ALIGN trial)1 was recently stopped because dabigatran etexilate mesylate users were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. There was also more bleeding after valve surgery in the dabigatran etexilate mesylate users than in the warfarin users.

Dabigatran etexilate mesylate is not approved for patients with atrial fibrillation caused by heart valve problems. FDA is requiring a contraindication (a warning against use) of dabigatran etexilate mesylate in patients with mechanical heart valves.

BACKGROUND:Dabigatran etexilate mesylate is a blood-thinning medication used to reduce the risk of stroke and blood clots in patients with a specific condition called non-valvular atrial fibrillation (AF), a common heart rhythm abnormality that causes the upper chambers of the heart, or atria, to beat rapidly and irregularly. Dabigatran etexilate mesylate is not indicated for patients with atrial fibrillation caused by heart valve problems.

RECOMMENDATION:Health care professionals should promptly transition any patient with a mechanical heart valve who is taking Dabigatran etexilate mesylate to another medication. The use of dabigatran etexilate mesylate in patients with another type of valve replacement made of natural biological tissue, known as a bioprosthetic valves, has not been evaluated and cannot be recommended. Patients with all types of prosthetic heart valve replacements taking dabigatran etexilate mesylate should talk to their health care professional as soon as possible to determine the most appropriate anticoagulation treatment. Patients should not stop taking anticoagulant medications without guidance from their health care professional; stopping dabigatran etexilate mesylate or other anticoagulants suddenly can increase the risk of blood clots and stroke. For more information visit the FDA website at: Web Siteand Web Site.

[UPDATED 11/02/2012] The FDA evaluated new information about the risk of serious bleeding associated with use of the anticoagulants (blood thinners) dabigatran (Pradaxa) and warfarin (Coumadin, Jantoven, and generics). This assessment was done using insurance claims and administrative data from FDA's Mini-Sentinel pilot of the Sentinel Initiative. The results of this assessment indicate that bleeding rates associated with new use of dabigatran 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 dabigatran (the RE-LY trial). FDA is continuing to evaluate multiple sources of data in the ongoing safety review of this issue. See the Data Summary in the 11/02/2012 Drug Safety Communication at: Web Sitefor additional information.

FDA has not changed its recommendations regarding dabigatran. Dabigatran provides an important health benefit when used as directed. Healthcare professionals who prescribe dabigatran should carefully follow the dosing recommendations in the drug label, especially for patients with renal impairment (when kidneys don't function normally) to reduce the risk of bleeding. Patients with atrial fibrillation should not stop taking dabigatran without first talking to their healthcare professional. Stopping use of anticoagulant medications such as dabigatran can increase the risk of stroke. Strokes can lead to permanent disability and death. For more information visit the FDA website at: Web Siteand Web Site.

WHY is this medicine prescribed?

Dabigatran is used to help prevent strokes or serious blood clots in people who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) without heart valve disease. Dabigatran is in a class of anticoagulant (''blood thinner'') medications called direct thrombin inhibitors. It works by preventing blood clots from forming in the body.

HOW should this medicine be used?

Dabigatran comes as a capsule to take by mouth. It is usually taken with or without food twice a day. Take dabigatran at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dabigatran exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole; do not split, chew, or crush them. Do not open the capsules and sprinkle the contents on food or into drinks.

Dabigatran will help prevent strokes and blood clots only as long as you continue to take it. Continue to take dabigatran even if you feel well. Make sure to refill your prescription before you run out of medication so that you will not miss doses of dabigatran. Do not stop taking dabigatran without talking to your doctor. If you suddenly stop taking dabigatran, the risk that you will have a stroke may increase.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with dabigatran and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What SPECIAL PRECAUTIONS should I follow?

Before taking dabigatran,

• tell your doctor and pharmacist if you are allergic to dabigatran, any other medications, or any of the ingredients in dabigatran capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven), ongoing use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve), clopidogrel (Plavix), dronedarone (Multaq), heparin, ketoconazole (Nizoral), prasugrel (Effient), and rifampin (Rifadin, Rimactane). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have recently noticed any unusual bruising or bleeding. Your doctor may tell you not to take dabigatran.
• tell your doctor if you are 75 years of age or older; if you have or have ever had a bleeding problem, bleeding or an ulcer in your stomach or intestine; or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dabigatran, call your doctor. Taking dabigatran may increase the risk that you will experience severe bleeding during labor and delivery.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking dabigatran.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it. However, if you remember the missed dose less than 6 hours before your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture. Throw away any medication that is outdated or no longer needed, and throw away any medication that is left in the container 4 months after you opened it. Talk to your pharmacist about the proper disposal of your medication.

What should I do in case of OVERDOSE?

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

• unusual bruising or bleeding
• pink or brown urine
• red or black, tarry stools
• vomiting material that is bloody or looks like coffee grounds
• coughing up blood

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to dabigatran.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.

Selected Revisions: February 15, 2013.