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What is Coumadin (warfarin)?
- treat deep vein thrombosis (DVT) to prevent extension of the clot, and to reduce the risk of pulmonary embolism;
- to prevent further emboli in patients with pulmonary embolism;
- to reduce the risk of strokes, and after a heart attack in patients with atrial fibrillation or artificial heart valves;
- to prevent blood clots from forming in certain orthopedic surgeries such as knee or hip replacements; and
- to prevent closure of coronary artery stents due to clotting.
Coumadin 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. Coumadin is important in preventing the formation of blood clots, preventing extension of clots already formed, and minimizing the risk of embolization of blood clots to other vital organs such as the lungs and brain.
Common side effects of Coumadin include:
- hair loss,
- yellowing of eyes and skin (jaundice), and
- purple, painful toes.
Serious side effects of Coumadin include:
- severe bleeding and necrosis (gangrene) of the skin.
- 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.
Drug interactions of Coumadin which can increase the effect of Coumadin by reducing its breakdown in the body include:
- metronidazole miconazole,
- indinavir, and
Drugs that may reduce the effect of Coumadin by increasing its breakdown include:
Bleeding is increased when Coumadin is taken with other anticoagulants, antiplatelet drugs such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and serotonin reuptake inhibitors (SSRIs). 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 Coumadin.
Coumadin should be avoided by pregnant women or women who may become pregnant. Birth defects and fetal bleeding have been reported. Available evidence suggests that Coumadin is not secreted in breast milk. Consult your doctor before breastfeeding.
What are the important side effects of Coumadin (warfarin)?
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:
Signs of overdose include:
Coumadin (warfarin) side effects list for healthcare professionals
The following serious adverse reactions to Coumadin are discussed in greater detail in other sections of the labeling:
- Tissue Necrosis
- Acute Kidney Injury
- Systemic Atheroemboli and Cholesterol Microemboli
- Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS
- Other Clinical Settings with Increased Risks
Other adverse reactions to Coumadin include:
- Immune system disorders: hypersensitivity/allergic reactions (including urticaria and anaphylactic reactions)
- Vascular disorders: vasculitis
- Hepatobiliary disorders: hepatitis, elevated liver enzymes. Cholestatic hepatitis has been associated with concomitant administration of Coumadin and ticlopidine.
- Gastrointestinal disorders: nausea, vomiting, diarrhea, taste perversion, abdominal pain, flatulence, bloating
- Skin disorders: rash, dermatitis (including bullous eruptions), pruritus, alopecia
- Respiratory disorders: tracheal or tracheobronchial calcification
- General disorders: chills
What drugs interact with Coumadin (warfarin)?
Drugs may interact with Coumadin through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with Coumadin are:
- synergism (impaired hemostasis,
- reduced clotting factor synthesis),
- competitive antagonism (vitamin K), and
- alteration of the physiologic control loop for vitamin K metabolism (hereditary resistance).
Pharmacokinetic mechanisms for drug interactions with Coumadin are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism. More frequent INR monitoring should be performed when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs, including drugs intended for short-term use (e.g., antibiotics, antifungals, corticosteroids).
Consult the labeling of all concurrently used drugs to obtain further information about interactions with Coumadin or adverse reactions pertaining to bleeding.
CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. The more potent warfarin S-enantiomer is metabolized by CYP2C9 while the R-enantiomer is metabolized by CYP1A2 and 3A4.
- Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin.
- Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin.
Examples of inhibitors and inducers of CYP2C9, 1A2, and 3A4 are below in Table 2; however, this list should not be considered all-inclusive. Consult the labeling of all concurrently used drugs to obtain further information about CYP450 interaction potential. The CYP450 inhibition and induction potential should be considered when starting, stopping, or changing dose of concomitant medications. Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer.
Table 2: Examples of CYP450 Interactions with Warfarin
|CYP2C9||amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast||aprepitant, bosentan, carbamazepine, phenobarbital, rifampin|
|CYP1A2||acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton||montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking|
|CYP3A4||alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton||armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide|
Drugs That Increase Bleeding Risk
Examples of drugs known to increase the risk of bleeding are presented in Table 3. Because bleeding risk is increased when these drugs are used concomitantly with warfarin, closely monitor patients receiving any such drug with warfarin.
Table 3: Drugs that Can Increase the Risk of Bleeding
|Drug Class||Specific Drugs|
|Anticoagulants||argatroban, dabigatran, bivalirudin, desirudin, heparin, lepirudin|
|Antiplatelet Agents||aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine|
|Nonsteroidal Anti-Inflammatory Agents||celecoxib, diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, oxaprozin, piroxicam, sulindac|
|Serotonin Reuptake Inhibitors||citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone|
Antibiotics And Antifungals
There have been reports of changes in INR in patients taking warfarin and antibiotics or antifungals, but clinical pharmacokinetic studies have not shown consistent effects of these agents on plasma concentrations of warfarin.
Closely monitor INR when starting or stopping any antibiotic or antifungal in patients taking warfarin.
Botanical (Herbal) Products And Foods
More frequent INR monitoring should be performed when starting or stopping botanicals.
Few adequate, well-controlled studies evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and Coumadin exist. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation.
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of Coumadin. Conversely, some botanicals may decrease the effects of Coumadin (e.g., co-enzyme Q10, St. John ’s wort, ginseng). Some botanicals and foods can interact with Coumadin through CYP450 interactions (e.g., echinacea, grapefruit juice, ginkgo, goldenseal, St. John’s wort).
The amount of vitamin K in food may affect therapy with Coumadin. Advise patients taking Coumadin to eat a normal, balanced diet maintaining a consistent amount of vitamin K. Patients taking Coumadin should avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables.
Coumadin (warfarin) is an oral anticoagulant, a drug that inhibits the clotting of blood. Coumadin is used to treat deep vein thrombosis (DVT), pulmonary embolism, reduce the risk of stroke, and more. Common side effects of Coumadin include bleeding, rash, hair loss, bloating, diarrhea, yellowing of eyes and skin (jaundice), and purple, painful toes. Coumadin should be avoided by pregnant women or women who may become pregnant. Birth defects and fetal bleeding have been reported. Available evidence suggests that Coumadin is not secreted in breast milk. Consult your doctor before breastfeeding.
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Related Disease Conditions
Second Source article from Government
Deep Vein Thrombosis (DVT, Blood Clot in the Legs)
Deep vein thrombosis (DVT) is a blood clot in the deep veins, and can be caused by broken bones, trauma to a limb, immobility, medications, smoking, cancer, genetic predisposition, and cancer. Symptoms of a deep vein thrombosis in a leg are swelling, tenderness, redness, warmth, and pain. Treatments for DVT include medications and surgery.
Pulmonary Embolism (Blood Clot in the Lung)
A pulmonary embolism (PE) occurs when a piece of a blood clot from deep vein thrombosis (DVT) breaks off and travels to an artery in the lung where it blocks the artery and damages the lung. The most common symptoms of a pulmonary embolism are shortness of breath, chest pain, and a rapid heart rate. Causes of pulmonary embolism include prolonged immobilization, certain medications, smoking, cancer, pregnancy, and surgery. Pulmonary embolism can cause death if not treated promptly.
Blood Clots (in the Leg)
Blood clots can occur in the venous and arterial vascular system. Blood clots can form in the heart, legs, arteries, veins, bladder, urinary tract and uterus. Risk factors for causes of blood clots include high blood pressure and cholesterol, diabetes, smoking, and family history. Symptoms of a blood clot depend on the location of the clot. Some blood clots are a medical emergency. Blood clots are treated depending upon the cause of the clot. Blood clots can be prevented by lowering the risk factors for developing blood clots.
DVT (Deep Vein Thrombosis) During Pregnancy
Deep vein thrombosis or DVT is a condition in which a blood clot becomes embedded in one of the deep veins of the arms, thighs, pelvis, or lower legs. Warning signs and symptoms of DVT include pain, warmth, redness, swelling, leg cramps, and worsening leg pain in the affected extremity. Many conditions and other factors can cause DVTs, for example, during pregnancy including postpartum (6-8 weeks after delivery of the baby), obesity, heart attacks or heart failure, cancer, birth control pills (oral contraceptives), recent surgery, high altitudes, and advanced age. Treatment guidelines for DVT diagnosed during pregnancy is anticoagulation (anti-clotting) drugs, usually, low-molecular-weight heparins. DVT treatment may need to be continued postpartum. Warfarin (Coumadin, Jantoven) should not be used to treat DVT during pregnancy because it can harm the developing fetus.
Treatment & Diagnosis
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Medications & Supplements
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.