[Posted 05/13/2014]ISSUE:The FDA recently completed a new study in Medicare patients comparing dabigatran (Pradaxa) to warfarin, for risk of ischemic or clot-related stroke, bleeding in the brain, major gastrointestinal (GI) bleeding, myocardial infarction (MI), and death. The new study included information from more than 134,000 Medicare patients, 65 years or older, and found that among new users of blood-thinning drugs, dabigatran was associated with a lower risk of clot-related strokes, bleeding in the brain, and death, than warfarin. The study also found an increased risk of major gastrointestinal bleeding with use of dabigatran as compared to warfarin. The MI risk was similar for the two drugs.
Importantly, the new study is based on a much larger and older patient population than those used in FDA's earlier review of post-market data, and employed a more sophisticated analytical method to capture and analyze the events of concern. This study's findings, except with regard to MI, are consistent with the clinical trial results that provided the basis for dabigatran's approval. As a result of these latest findings, the FDA still considers dabigatran to have a favorable benefit to risk profile and have made no changes to the current label or recommendations for use.
BACKGROUND:Dabigatran and warfarin are used to reduce the risk of stroke and blood clots in patients with a common type of abnormal heart rhythm called non-valvular atrial fibrillation (AF).
RECOMMENDATION:Patients should not stop taking dabigatran (or warfarin) without first talking with their health care professionals. Stopping the use of blood-thinning medications such as dabigatran and warfarin can increase the risk of stroke and lead to permanent disability and death. Health care professionals who prescribe dabigatran should continue to follow the dosing recommendations in the drug label. For more information visit the FDA website at: Web Siteand Web Site.
If you have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) and are taking dabigatran to help prevent strokes or serious blood clots, you are at a higher risk of having a stroke after you stop taking this medication. Do not stop taking dabigatran without talking to your doctor. Continue to take dabigatran even if you feel well. Be sure to refill your prescription before you run out of medication so that you will not miss any doses of dabigatran. If you need to stop taking dabigatran, your doctor may prescribe another anticoagulant ('blood thinner') to help prevent a blood clot from forming and causing you to have a stroke.
If you have epidural or spinal anesthesia or a spinal puncture while taking a 'blood thinner' such as dabigatran, you are at risk of having a blood clot form in or around your spine that could cause you to become paralyzed. Tell your doctor if you have an epidural catheter that is left in your body or have or have ever had repeated epidural or spinal punctures, spinal deformity, or spinal surgery. Tell your doctor and pharmacist if you are taking any of the following: anagrelide (Agrylin), aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin), indomethacin (Indocin, Tivorbex), ketoprofen, and naproxen (Aleve, Anaprox, others), cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine), eptifibatide (Integrilin), heparin, prasugrel (Effient), ticagrelor (Brilinta), ticlopidine, tirofiban (Aggrastat), and warfarin (Coumadin, Jantoven). If you experience any of the following symptoms, call your doctor immediately: back pain, muscle weakness (especially in your legs and feet), numbness or tingling, (especially in your legs), or loss of control of your bowels or bladder.
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to dabigatran.
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.
Dabigatran is used to treat deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in patients who have been treated with an injectable anticoagulant (''blood thinner''). It is also used to reduce the risk of a PE and DVT from happening again after initial treatment is completed. 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 medications called direct thrombin inhibitors. It works by preventing blood clots from forming in the body.
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 with a whole glass of water; 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.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
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: dronedarone (Multaq), ketoconazole (Nizoral), and rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.tell your doctor if you have had a valve in your heart replaced or if you have recently noticed any unusual bruising or bleeding. Your doctor probably will 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 breastfeeding. 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.
Unless your doctor tells you otherwise, continue your normal diet.
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.
Dabigatran may cause side effects. Tell your doctor if any of these symptoms occur: stomach painupset stomachheartburnnausea
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment: unusual bruising or bleedingpink or brown urinered or black, tarry stoolscoughing up bloodvomiting material that is bloody or looks like coffee groundsbleeding from the gumsfrequent nosebleedsheavy menstrual bleedingbleeding from a cut that lasts longer than normaljoint pain or swellingheadachedizziness or feeling faintweaknesshivesrashitchingdifficulty breathing or swallowingchest pain or tightnessswelling of the face, throat, tongue, lips, eyes, arms, hands, feet, ankles, or lower legs
Dabigatran may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Do not store dabigatran in a pillbox or pill organizer. Store it at room temperature and away from excess heat and moisture. Open only one bottle of dabigatran at a time. Finish your opened bottle of dabigatran before opening a new bottle). 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.
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 bleedingpink or brown urinered or black, tarry stoolsvomiting material that is bloody or looks like coffee groundscoughing up blood
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: July 15, 2014.