Plavix (clopidogrel) vs. Coumadin (warfarin): What’s the difference?
- Clopidogrel and warfarin are blood thinners used to prevent blood clots.
- A brand name for clopidogrel is Plavix.
- Brand names for warfarin include Coumadin and Jantoven.
- Side effects of clopidogrel and warfarin that are similar include increased bleeding, rash, and diarrhea.
- Side effects of clopidogrel that are different from warfarin include itching, abdominal pain, headache, chest pain, muscle aches, dizziness, allergic reactions, pancreatitis, and liver failure.
- Side effects of warfarin that are different from clopidogrel include necrosis (gangrene) of the skin, purple and painful toes, hair loss, bloating, and yellowing of eyes and skin (jaundice).
What is clopidogrel? What is warfarin?
Clopidogrel is an anti-platelet drug, which is a type of blood thinner, used to prevent strokes, heart attacks, and death in high-risk patients who have had a previous stroke, unstable angina, heart attack, or have peripheral arterial disease (PAD). Clopidogrel works to prevent blood clots by binding to P2Y12 receptors on platelets and preventing adenosine diphosphate (ADP) from activating them. Clopidogrel belongs to the P2Y12 inhibitor drug class, which also includes ticagrelor (Brilinta) and prasugrel (Effient). Clopidogrel is similar to ticlopidine (Ticlid) in chemical structure and in the way it works.
Warfarin is an anticoagulant (blood thinner) prevents the formation of blood clots by reducing the production of factors by the liver that promote clotting, factors II, VII, IX, and X, and the anticoagulant proteins C and S. The production of these factors by the liver are dependent on adequate amounts of vitamin K. Warfarin reduces the production of the factors because it antagonizes vitamin K. Warfarin is used to treat deep vein thrombosis (DVT) to prevent extension of the clot and to reduce the risk of pulmonary embolism, pulmonary embolism to prevent further emboli, and in patients with atrial fibrillation or artificial heart valves to reduce the risk of strokes, and after a heart attack. Warfarin also is helpful in preventing blood clots from forming in certain orthopedic surgeries such as knee or hip replacements. Warfarin is used in preventing closure of coronary artery stents due to clotting.
Deep vein thrombosis (DVT) occurs in the _______________.
What are the side effects of clopidogrel and warfarin?
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.
The two most serious side effects of warfarin are:
- Necrosis (gangrene) of the skin
Bleeding can occur in any organ or tissue. Bleeding around the brain can cause severe headache and paralysis. Bleeding in the joints can cause joint pain and swelling. Bleeding in the stomach or intestines can cause weakness, fainting spells, black tarry stools, vomiting of blood, or coffee ground material. Bleeding in the kidneys can cause back pain and blood in urine.
Other side effects include:
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What is the dosage of clopidogrel vs. warfarin?
Clopidogrel bisulfate usually is taken once daily. It can be taken with or without food. Clopidogrel is activated by enzymes in the liver to its active form. Individuals who have reduced activity of liver enzymes that activate clopidogrel due to liver disease may not adequately respond to clopidogrel. Alternative treatments should be used for these patients. The recommended dose for treating unstable angina or heart attack is 300 mg initially followed by 75 mg daily in combination with 75-325 mg of aspirin. Peripheral arterial disease or recent stroke is treated with 75 mg daily.
- Warfarin may be taken with or without food.
- Since warfarin is metabolized (inactivated) by the liver and then excreted by the kidneys, dosages need to be lowered in patients with liver and kidney dysfunction.
- Frequent blood tests (INR test) are performed to measure the effect of warfarin and to adjust dosing.
- There are published INR ranges for the various uses of warfarin.
- Treatment usually is started at 2 to 5 mg once daily and the dose is adjusted based in INR tests.
- Patients typically require 2 to 10 mg of warfarin daily.
What drugs interact with clopidogrel and warfarin?
The combination of clopidogrel with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil, Nuprin), naproxen (Naprosyn, Aleve), diclofenac (Voltaren), etodolac (Lodine), nabumetone (Relafen), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis; Oruvail), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and mefenamic acid (Ponstel) may increase the risk of stomach and intestinal bleeding.
Combining clopidogrel with warfarin (Coumadin) or other drugs that cause bleeding increases the risk of bleeding.
Clopidogrel is converted to its active form by enzymes in the liver. Drugs that reduce the activity of these enzymes, for example, omeprazole (Prilosec, Zegerid) or esomeprazole (Nexium) may reduce the activity of clopidogrel and should not be used with clopidogrel. Other drugs that also may react with clopidogrel in a similar fashion include:
- fluoxetine (Prozac, Sarafem),
- cimetidine (Tagamet),
- fluconazole (Diflucan),
- ketoconazole (Nizoral, Extina, Xolegel, Kuric),
- voriconazole (Vfend),
- ethaverine (Ethatab, Ethavex),
- felbamate (Felbatol), and
- fluvoxamine (Luvox).
- Many drugs, both prescription and nonprescription (OTC), can affect the anticoagulant action of warfarin or increase the risk of bleeding. Patients on warfarin should regularly consult their doctor before instituting any medications on their own.
- It also is advisable for patients on warfarin to carry identification such as bracelets to alert other health professionals to the presence of anticoagulation.
- A few examples of drugs that interact with warfarin are:
- Drugs that increase the effect of warfarin by reducing the breakdown of warfarin include amiodarone (Cordarone), trimethoprim/sulfamethoxazole (Bactrim), fluconazole (Diflucan), itraconazole (Sporanox), fluvastatin, fluvoxamine, metronidazole miconazole, voriconazole (Vfend), zafirlukast (Accolate), ciprofloxacin (Cipro), cimetidine, atorvastatin (Lipitor), clarithromycin (Biaxin), fluoxetine (Prozac), indinavir (Crixivan), and ritonavir (Norvir).
- Drugs that may reduce the effect of warfarin by increasing its breakdown include St. John's wort, carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol), rifampin, bosentan (Tracleer), and prednisone.
- Bleeding is increased by other anticoagulants such as heparin, argatroban (Acova), dabigatran (Pradaxa), and others; antiplatelet drugs such as aspirin and other nonsteroidal anti-inflammatory drugs (for example, ibuprofen [Motrin], naproxen [Alleve]), clopidogrel (Plavix), and prasugrel (Effient); serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and paroxetine (Paxil). Garlic and ginkgo also increase the risk of bleeding because they cause bleeding when taken alone.
- Foods with high vitamin K content (for example, green leafy vegetables) reduce the effect of warfarin. Maintenance of a consistent intake of vitamin K containing foods is important to avoid fluctuations in the effect of warfarin
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Are clopidogrel and warfarin safe to use while pregnant or breastfeeding?
• There are no adequate studies of clopidogrel in pregnant women.
• Studies in rats have shown that clopidogrel appears in breast milk; however, it is not known whether it also appears in human breast milk. Because of a potential for side effects in the nursing infant, the physician must weigh the potential benefits and possible risks before prescribing clopidogrel to nursing mothers.
• Warfarin should be avoided by pregnant women or women who may become pregnant. Birth defects and fetal bleeding have been reported.
• Available evidence suggests that warfarin is not secreted in breast milk.