[Posted 11/16/2014] ISSUE: FDA is evaluating preliminary data from a clinical trial showing that treatment for 30 months with dual antiplatelet blood-thinning therapy decreased the risk of heart attacks and clot formation in stents, but there was an increased overall risk of death compared to 12 months of treatment. The clinical trial compared 30 months versus 12 months of treatment with dual antiplatelet therapy consisting of aspirin plus either clopidogrel (Plavix) or prasugrel (Effient), following implantation of drug-eluting coronary stents. These stents are small, medicine-coated tubes inserted into narrowed arteries in the heart to keep them open and maintain blood flow to the heart. Clopidogrel and prasugrel are important medicines used to prevent heart attacks, strokes, and other clot-related diseases.
FDA believes the benefits of clopidogrel (Plavix) and prasugrel (Effient) therapy continue to outweigh their potential risks when used for approved uses.
BACKGROUND: The Dual Antiplatelet Therapy (DAPT) trial was published in the New England Journal of Medicine on November 16, 2014. FDA has not reviewed the trial results or reached any conclusions based on the findings from this clinical trial. We are communicating this safety information while we continue to evaluate the results from this trial and other available data. We will communicate our final conclusions and recommendations when our evaluation is complete.
RECOMMENDATION:Health care professionals should not change the way they prescribe these drugs at this time. Patients should not stop taking these drugs because doing so may result in an increased risk of heart attacks, blood clots, strokes, and other major cardiovascular problems. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Clopidogrel must be changed to an active form in your body so that it can treat your condition. Some people do not change clopidogrel to its active form in the body as well as other people. Because the medication does not work as well in these people, they may be at a higher risk of having a heart attack or stroke. There are tests available to identify people who have trouble changing clopidogrel to an active form. Talk to your doctor about whether you should be tested. If you are found to have difficulty converting clopidogrel to its active form, your doctor may change your dose of clopidogrel or tell you not to take clopidogrel.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with clopidogrel 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 (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of taking clopidogrel.
Why is this medication prescribed?
Clopidogrel is used alone or with aspirin to prevent serious or life-threatening problems with the heart and blood vessels in people who have had a stroke, heart attack, or severe chest pain. This includes people who have percutaneous coronary intervention (PCI; angioplasty; a type of heart surgery) that may involve inserting coronary stents (metal tubes surgically placed in clogged blood vessels to improve blood flow) or who have coronary artery bypass grafting (CABG; a type of heart surgery). Clopidogrel is also used to prevent serious or life-threatening problems with the heart and blood vessels in people who have peripheral arterial disease (poor circulation in the blood vessels that supply blood to the legs). Clopidogrel is in a class of medications called antiplatelet medications. It works by preventing platelets (a type of blood cell) from collecting and forming clots that may cause a heart attack or stroke.
How should this medicine be used?
Clopidogrel comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take clopidogrel at around the same time 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 clopidogrel exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Clopidogrel will help prevent serious problems with your heart and blood vessels only as long as you take the medication. Continue to take clopidogrel even if you feel well. Do not stop taking clopidogrel without talking to your doctor. If you stop taking clopidogrel, there is a higher risk that you may have a heart attack or stroke. If you have a stent, there is also a higher risk that you could develop a blood clot in the stent if you stop taking clopidogrel too soon.
Other uses for this medicine
Clopidogrel is also sometimes used to prevent blood clots in people with atrial fibrillation (a condition in which the heart beats irregularly). Talk to your doctor about the possible risks of using this medication for your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking clopidogrel,
- tell your doctor and pharmacist if you are allergic to clopidogrel, prasugrel (Effient), ticlopidine (Ticlid), any other medications, or any ingredient in clopidogrel tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what other 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); aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn); cilostazol (Pletal);esomeprazole (Nexium); etravirine (Intelence); omeprazole (Prilosec, Prilosec OTC, Zegerid); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), sibutramine (Meridia), and venlafaxine (Effexor). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have bleeding ulcers (sores in the lining of the stomach or small intestine that are bleeding), bleeding in the brain, or any other condition that causes severe bleeding. Your doctor may tell you that you should not take clopidogrel.
- tell your doctor if you have recently been injured and if you have or have ever had liver or kidney disease or any condition that may cause bleeding, including stomach problems such as ulcers and certain eye problems.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking clopidogrel, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking clopidogrel.
- you should know that you may bleed more easily or for a longer time than usual while you are taking clopidogrel. Be careful not to cut or hurt yourself while you are taking clopidogrel.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next 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 medication cause?
Clopidogrel may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- excessive tiredness
- stomach pain
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:
- difficulty breathing or swallowing
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- black and tarry stools
- red blood in stools
- bloody vomit
- vomit that looks like coffee grounds
- unusual bleeding or bruising
- slow or difficult speech
- weakness or numbness of an arm or a leg
- changes in vision
- shortness of breath
- fast heartbeat
- pale skin
- purple patches or bleeding under the skin
- yellowing of the skin or eyes
Clopidogrel 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 http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].
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 (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/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
What other information should I know?
Keep all appointments with your doctor.
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.