Warfarin Side Effects

Some side effects of warfarin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to warfarin: oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking warfarin: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Warfarin may cause you to bleed more easily, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have any unusual bleeding, or bleeding that will not stop. You may also have bleeding on the inside of your body, such as in your stomach or intestines. Call your doctor at once if you have black or bloody stools, or if you cough up blood or vomit that looks like coffee grounds. These could be signs of bleeding in your digestive tract.

Call your doctor at once if you have:

• pain, swelling, hot or cold feeling, skin changes, or discoloration anywhere on your body;

• sudden and severe leg or foot pain, foot ulcer, purple toes or fingers;

• sudden headache, dizziness, or weakness;

• easy bruising, purple or red pinpoint spots under your skin, bleeding from wounds or needle injections;;

• pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

• dark urine, jaundice (yellowing of the skin or eyes);

• little or no urinating;

• numbness or muscle weakness; or

• pain in your stomach, back, or sides.

Common side effects may include:

• nausea, vomiting, mild stomach pain;

• bloating, gas; or

• altered sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to warfarin: compounding powder, intravenous powder for injection, oral tablet

Hematologic

Hematologic side effects including occult and overt bleeding or hemorrhage at any site have been reported the most frequently. Bleeding complications may present as paralysis, paresthesia, headache, chest, abdominal, joint, muscle or other pain, dizziness, shortness of breath, difficulty breathing or swallowing, unexplained swelling, weakness, hypotension, or unexplained shock. Bleeding may result in hematomas, melena, hematuria, ecchymoses, epistaxis, and hematemesis. Spontaneous intraspinal hematomas, spinal cord hemorrhage, gastrointestinal hemorrhage, intracranial hemorrhage, ocular hemorrhage, intra-abdominal hemorrhage, hemopericardium, compartment syndrome following blunt trauma, and other serious bleeding events have been reported. Anemia has been reported infrequently.

Warfarin-induced intracranial hemorrhage is associated with a high rate of mortality and disability compared with extracranial hemorrhages.

Hematologic risk factors have included history of stroke, a serious comorbid condition, a history of gastrointestinal bleeding, atrial fibrillation, advanced age, and concomitant use of aspirin. In addition, patients with genetic variations in the CYP450 2C9 and VKORC1 enzymes are at a higher risk of bleeding than those without the variation.

A meta-analysis of five randomized controlled trials compared the efficacy and safety of combined oral anticoagulation and antiplatelet therapy versus oral anticoagulants alone after prosthetic heart valve replacement and found an increased risk of general hemorrhage (65%) and gastrointestinal hemorrhage (250%). Embolism and stroke were significantly decreased. The authors conclude that the benefits of decreased risk of thromboembolic events outweigh the toxic effects of combined anticoagulation and antiplatelet therapy.

The results of large observational cohort study (n=13,559) indicate that in patients with nonvalvular atrial fibrillation, the risk of major hemorrhage increases with age, particularly intracranial hemorrhage, whether or not they are receiving warfarin. In patients aged 80 and older the risk of intracranial hemorrhage increases sharply. Also, this study found that among anticoagulated patients with atrial fibrillation, intracranial hemorrhages were responsible for nearly 90% of the deaths from warfarin-associated hemorrhage and the majority of disability among survivors.

Dermatologic

Dermatologic side effects including necrosis of the skin and other tissues have been reported in 0.1% to 1.0% of patients. Dermatitis, urticaria, alopecia, rash, bullous eruptions, pruritus, and pallor have been reported infrequently.

Warfarin-induced skin necrosis predominantly affects obese women (4-fold greater occurrence in women) and typically occurs within 10 days of the initiation of therapy, but has occurred after several months or several years of therapy. The majority of lesions (80%) occur in areas with abundant adipose such as the thighs, breasts, abdomen, buttocks, and the extremities. The lesions are usually painful, abrupt in onset, erythematous, purpuric, and sharply demarcated. The proposed mechanism of warfarin-induced skin necrosis involves an imbalance between protein C or protein S and vitamin K-dependent clotting factors. The lesions may resolve spontaneously or progress to form hemorrhagic bullae with subsequent necrosis. Generally, warfarin is withheld; however, discontinuation does not affect lesion progression. Some patients have safely resumed warfarin therapy, but the recommended management in patients who require long-term anticoagulation is resumption of warfarin at a lower dose in conjunction with heparin bridge therapy. The dosage of warfarin should be slowly titrated until a therapeutic INR is reached.

One case of warfarin-induced skin necrosis of the eyelids has been reported. In this case, the patient developed bilateral periorbital ecchymoses with full-thickness necrotic lesions in the medial canthal region.

Other

Other side effects have been reported infrequently. These have included purple toe syndrome.

Cardiovascular

Cardiovascular side effects have included systemic atheroemboli and cholesterol microemboli, which present with a variety of signs and symptoms. These have included purple toe syndrome, livedo reticularis (blue tingeing of the skin), rash, gangrene, abrupt and intense pain in the leg, foot, or toes, foot ulcers, myalgia, penile gangrene, abdominal pain, flank or back pain, hematuria, renal insufficiency, hypertension, cerebral ischemia, spinal cord infarction, pancreatitis, symptoms simulating polyarteritis, or any other sequelae of vascular compromise due to embolic occlusion. Hemopericardium and cardiac tamponade have also been reported. Hypotension, edema, angina syndrome, and chest pain have been reported infrequently.

Hepatic

Hepatic side effects have been reported infrequently. These have included jaundice, intrahepatic cholestasis, hepatitis, and elevated liver enzymes.

Renal

Renal side effects have been reported infrequently. These have included hematuria, acute renal failure due to interstitial nephritis, and renal hematomas.

Gastrointestinal

A meta-analysis of five randomized controlled trials compared the efficacy and safety of combined oral anticoagulation and antiplatelet therapy versus oral anticoagulants alone after prosthetic heart valve replacement and found an increased risk of general hemorrhage (65%) and gastrointestinal hemorrhage (250%). Embolism and stroke were significantly decreased. The authors conclude that the benefits of decreased risk of thromboembolic events outweigh the toxic effects of combined anticoagulation and antiplatelet therapy.

Gastrointestinal side effects have been reported infrequently. Nausea, diarrhea, abdominal cramping, vomiting, and flatulence/bloating have been reported. Gastrointestinal bleed has occurred when warfarin was combined with aspirin for antithrombotic effects after placement of heart valves.

Genitourinary

Warfarin-induced priapism has been reported. In one case report, a 16 year old male patient had been treated with warfarin for a deep venous thrombosis in his leg. The patient experienced a hypercoagulable state upon initiation of warfarin therapy because he also had an undocumented protein C deficiency. This led to an increased risk of thromboembolism that manifested as priapism and skin necrosis.

Genitourinary side effects have included priapism.

Hypersensitivity

Hypersensitivity reactions including anaphylactic reactions have been reported infrequently. A case of leukocytoclastic cutaneous vasculitis has been reported.

Nervous system

Nervous system side effects have been reported rarely. These have included fever, fatigue, lethargy, malaise, asthenia, pain, headache, dizziness, taste perversion, cold intolerance, and paresthesia including feeling cold and chills, syncope, loss of consciousness, and coma.

Respiratory

Respiratory side effects have been reported rarely. These have included tracheal or tracheobronchial calcification.

Ocular

Ocular side effects have included subconjunctival hemorrhage and retinal hemorrhage.

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