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Does Plavix (clopidogrel bisulfate) cause side effects?
Plavix (clopidogrel bisulfate) is an antiplatelet drug used to prevent strokes, heart attacks, and death in individuals who have had a previous stroke, unstable angina, heart attack or have peripheral arterial disease (PAD).
The combination of Plavix and aspirin is better than aspirin or Plavix alone in preventing another heart attack but the risk of bleeding is higher. Plavix prevents blood clots by irreversibly binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets.
Plavix is similar to ticlopidine in chemical structure and in the way it works. Unlike ticlopidine, Plavix does not cause serious reductions of white cells in the blood and, therefore, routine blood testing to determine if the white blood cell count is low is not necessary during treatment.
The risk of heart attacks and strokes (which usually are caused by blood clots) is increased in patients with a recent history of stroke or heart attack, and patients with peripheral vascular disease.
Peripheral vascular disease is the same as atherosclerotic arterial disease or "hardening" of the arteries in which the arteries become narrowed. It frequently occurs in the legs and often causes claudication or pain in the legs upon walking. Plavix is used to reduce the risk of heart attacks and strokes in these patients.
Common side effects of Plavix include
Serious side effects of Plavix include
- severe bleeding,
- allergic reactions,
- liver failure, and rarely,
- severe reduction in white blood cell count and thrombotic thrombocytopenic purpura (TTP).
Drug interactions of Plavix include nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, etodolac, nabumetone, fenoprofen, flurbiprofen, indomethacin, ketoprofen, oxaprozin, piroxicam, sulindac, tolmetin, and mefenamic acid, because the combination may increase the risk of stomach and intestinal bleeding.
- Combining Plavix with warfarin or other drugs that cause bleeding increases the risk of bleeding. Plavix is converted to its active form by enzymes in the liver.
- Drugs that reduce the activity of these enzymes, for example, omeprazole or esomeprazole may reduce the activity of Plavix and should not be used with Plavix.
- Other drugs that also may react with Plavix in a similar fashion include fluoxetine, cimetidine, fluconazole, ketoconazole, voriconazole, ethaverine, felbamate, and fluvoxamine.
What are the important side effects of Plavix (clopidogrel bisulfate)?
The tolerability of clopidogrel is similar to that of aspirin. The more common side effects of clopidogrel are:
- Abdominal pain
- chest pain,
- muscle aches,
- severe bleeding,
- allergic reactions,
- pancreatitis, and
- liver failure.
Ticlopidine (Ticlid) is an antiplatelet medication quite similar to clopidogrel. It has been associated with a severe reduction in white blood cell count in between 0.8% and 1% of persons. The risk of this dangerous side effect with clopidogrel is about 0.04%, much less than with ticlopidine but twice that of aspirin.
Clopidogrel rarely causes a condition called thrombotic thrombocytopenic purpura (TTP) in one out of every 250,000 people. TTP is a serious condition in which blood clots form throughout the body.
Blood platelets, which participate in clotting, are consumed, and the result can be bleeding because enough platelets are no longer left to allow blood to clot normally. For comparison, the related drug, ticlodipine (Ticlid), causes TTP 17-50 times more frequently than clopidogrel.
Plavix (clopidogrel bisulfate) side effects list for healthcare professionals
The following serious adverse reactions are discussed below and elsewhere in the labeling:
- Thrombotic thrombocytopenic purpura
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions and durations of follow-up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Plavix has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for one year or more. The clinically important adverse reactions observed in trials comparing Plavix plus aspirin to placebo plus aspirin and trials comparing Plavix alone to aspirin alone are discussed below.
In CURE, Plavix use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1).
The incidence of intracranial hemorrhage (0.1%) and fatal bleeding (0.2%) were the same in both groups. Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise.
The overall incidence of bleeding is described in Table 1.
Table 1: CURE Incidence of Bleeding Complications (% patients)
|5 g/dL hemoglobin drop||0.9||0.9|
|Requiring surgical intervention||0.7||0.7|
|Requiring transfusion (≥4 units)||1.2||1.0|
|Other major bleeding||1.6||1.0|
|Intraocular bleeding with significant loss of vision||0.05||0.03|
|Requiring 2-3 units of blood||1.3||0.9|
|* Life-threatening and other major bleeding.
† Led to interruption of study medication.
In COMMIT, similar rates of major bleeding were observed in the Plavix and placebo groups, both of which also received aspirin (see Table 2).
Table 2: Incidence of Bleeding Events in COMMIT (% patients)
|Type of Bleeding||Plavix
|Major* noncerebral or cerebral bleeding||0.6||0.5||0.59|
|Other noncerebral bleeding (nonmajor)||3.6||3.1||0.005|
|Any noncerebral bleeding||3.9||3.4||0.004|
|* Major bleeds were cerebral bleeds or noncerebral bleeds thought to have caused death or that required transfusion.|
CAPRIE (Plavix Vs Aspirin)
- In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking Plavix versus 2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for Plavix compared to 0.5% for aspirin.
- Other bleeding events that were reported more frequently in the Plavix group were epistaxis and hematoma.
Other Adverse Events
- In CURE and CHARISMA, which compared Plavix plus aspirin to aspirin alone, there was no difference in the rate of adverse events (other than bleeding) between Plavix and placebo.
- In CAPRIE, which compared Plavix to aspirin, pruritus was more frequently reported in those taking Plavix. No other difference in the rate of adverse events (other than bleeding) was reported.
The following adverse reactions have been identified during postapproval use of Plavix. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hemorrhages, including those with fatal outcome, have been reported in patients treated with Plavix.
- Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP), acquired hemophilia A
- Gastrointestinal disorders: Colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis, gastric/duodenal ulcer, diarrhea
- General disorders and administration site condition: Fever
- Hepatobiliary disorders: Acute liver failure, hepatitis (noninfectious), abnormal liver function test
- Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness, insulin autoimmune syndrome, which can lead to severe hypoglycemia.
- Musculoskeletal, connective tissue and bone disorders: Myalgia, arthralgia, arthritis
- Nervous system disorders: Taste disorders, headache, ageusia
- Psychiatric disorders: Confusion, hallucinations
- Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, eosinophilic pneumonia
- Renal and urinary disorders: Increased creatinine levels
- Skin and subcutaneous tissue disorders: Maculopapular, erythematous or exfoliative rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis (AGEP), angioedema, drug-induced hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), erythema multiforme, lichen planus, generalized pruritus
- Vascular disorders: Vasculitis, hypotension
What drugs interact with Plavix (clopidogrel bisulfate)?
- Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition.
Omeprazole Or Esomeprazole
- Avoid concomitant use of Plavix with omeprazole or esomeprazole. In clinical studies, omeprazole was shown to reduce significantly the antiplatelet activity of Plavix when given concomitantly or 12 hours apart.
- A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with Plavix.
- Dexlansoprazole, lansoprazole, and pantoprazole had less effect on the antiplatelet activity of Plavix than did omeprazole or esomeprazole.
- As with other oral P2Y12 inhibitors, coadministration of opioid agonists delay and reduce the absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its metabolites.
- Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
- Coadministration of Plavix and NSAIDs increases the risk of gastrointestinal bleeding.
Warfarin (CYP2C9 Substrates)
- Although the administration of clopidogrel 75 mg per day did not modify the pharmacokinetics of S-warfarin (a CYP2C9 substrate) or INR in patients receiving long-term warfarin therapy, coadministration of Plavix with warfarin increases the risk of bleeding because of independent effects on hemostasis.
- However, at high concentrations in vitro, clopidogrel inhibits CYP2C9.
SSRIs And SNRIs
- Since selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) affect platelet activation, the concomitant administration of SSRIs and SNRIs with clopidogrel may increase the risk of bleeding.
Repaglinide (CYP2C8 Substrates)
- The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. Plavix can increase the systemic exposure to drugs that are primarily cleared by CYP2C8, thereby needing dose adjustment and appropriate monitoring.
- Plavix increased repaglinide exposures by 3.9-fold to 5.1-fold.
- Avoid concomitant use of repaglinide with Plavix. If concomitant use cannot be avoided, initiate repaglinide at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg. Increased frequency of glucose monitoring may be required during concomitant use.
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Related Disease Conditions
Heart disease (coronary artery disease) occurs when plaque builds up in the coronary arteries, the vessels that supply blood to the heart. Heart disease can lead to heart attack. Risk factors for heart disease include: Smoking High blood pressure High cholesterol Diabetes Family history Obesity Angina, shortness of breath, and sweating are just a few symptoms that may indicate a heart attack. Treatment of heart disease involves control of heart disease risk factors through lifestyle changes, medications, and/or stenting or bypass surgery. Heart disease can be prevented by controlling heart disease risk factors.
Heart Disease: Sudden Cardiac Death
Second Source WebMD Medical Reference
Stress and Heart Disease
The connection between stress and heart disease is not clear. Stress itself may be a risk factor, or high levels of stress may make risk factors for heart disease worse. The warning signs of stress can be physical, mental, emotional, or behavioral. Reducing stressors in an individuals life not only can lead to a more productive life, but may also decrease the risk for heart disease and causes of heart disease.
Heart Disease in Women
Heart disease in women has somewhat different symptoms, risk factors, and treatment compared to heart disease in men. Many women and health professionals are not aware of the risk factors for heart disease in women and may delay diagnosis and treatment. Lifestyle factors such as diet, exercise, tobacco use, overweight/obesity, stress, alcohol consumption, and depression influence heart disease risk in women. High blood pressure, high cholesterol, and diabetes also increase women's risk of heart disease. Electrocardiogram (EKG or ECG), stress-ECG, endothelial testing, ankle-brachial index (ABI), echocardiogram, nuclear imaging, electron beam CT, and lab tests to assess blood lipids and biomarkers of inflammation are used to diagnose heart disease. Early diagnosis and treatment of heart disease in women saves lives. Heart disease can be prevented and reversed with lifestyle changes.
Heart Disease Treatment in Women
Heart disease treatment in women should take into account female-specific guidelines that were developed by the American Heart Association. Risk factors and symptoms of heart disease in women differ from those in men. Treatment may include lifestyle modification (diet, exercise, weight management, smoking cessation, stress reduction), medications, percutaneous intervention procedure (PCI), and coronary artery bypass grafting (CABG). Heart disease is reversible with treatment.
Congenital Heart Defects
Congenital heart defects are heart problems that are present at birth. Genetics may play a role in some heart defects. Symptoms can range from nonexistent to severe and life-threatening. Fatigue, rapid breathing, and decreased blood circulation are a few possible symptoms of congenital heart defects. Many cases do not require any treatment. Procedures using catheters and surgery may be used to repair severe heart defects.
Smoking and Heart Disease
Smoking increases the risk of heart disease in women and men. Nicotine in cigarettes decrease oxygen to the heart, increases blood pressure, blood clots, and damages coronary arteries. Learn how to quit smoking today, to prolong your life.
Treatment & Diagnosis
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Medications & Supplements
- Aspirin vs. Plavix (clopidogrel)
- Plavix (clopidogrel) vs. Coumadin (warfarin)
- Plavix (clopidogrel) vs. Xarelto (rivaroxaban)
- Ibuprofen and Plavix (Side Effects and Interactions)
- clopidogrel bisulfate (Plavix)
- Coumadin vs. Plavix (Differences and Similarities)
- Plavix (clopidogrel) vs. Effient (prasurgrel)
- clopidogrel (Plavix) vs. heparin (Hemochron)
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.