Coumadin

Action

Interferes with synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X) and anticoagulant proteins C and S in liver

Availability

Injection: 5.4 mg/vial (2 mg/ml when reconstituted)

Tablets: 1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg

Indications and dosages

➣ Venous thrombosis; pulmonary embolism; atrial fibrillation; myocardial infarction (MI); thromboembolic complications of cardiac valve placement

Adults: Initially, 2.5 to 10 mg P.O. or I.V. daily for 2 to 4 days, then adjusted based on prothrombin time (PT) or International Normalized Ratio (INR). Usual maintenance dosage is 2 to 10 mg P.O. daily.

Dosage adjustment

• Elderly or debilitated patients

Off-label uses

• Acute coronary syndrome

• Intracoronary stent placement

• Prevention of catheter thrombosis

Contraindications

• Hypersensitivity to drug

• Uncontrolled bleeding

• Open wounds

• Severe hepatic disease

• Hemorrhagic or bleeding tendency

• Cerebrovascular hemorrhage

• Cerebral aneurysm or dissecting aorta

• Blood dyscrasias

• Pericarditis or pericardial effusion

• Bacterial endocarditis

• Malignant hypertension

• Recent brain, eye, or spinal cord injury or surgery

• Lumbar puncture and other procedures that may cause uncontrollable bleeding

• Major regional or lumbar block anesthesia

• Threatened abortion, eclampsia, preeclampsia

• Unsupervised senile, alcoholic, or psychotic patients

• Pregnancy, females of childbearing potential

Precautions

Use cautiously in:

• cancer, heparin-induced thrombocytopenia, moderate to severe renal impairment, moderate to severe hypertension, infectious GI disease, known or suspected deficiency in protein C-mediated anticoagulant response, polycythemia vera, vasculitis, severe diabetes mellitus

• indwelling catheter use

• history of poor compliance

• elderly or debilitated patients

• breastfeeding patients

• children younger than age 18 (safety and efficacy not established).

Administration

☞ Be aware that warfarin is a high-alert drug.

• Know that I.V. form is reserved for patients who can't tolerate oral form. I.V. and oral dosages are identical.

• For I.V. use, reconstitute vial with 2.7 ml of sterile water for injection; administer over 1 to 2 minutes. After reconstitution, drug is stable for 4 hours at room temperature.

• Be aware that vitamin K reverses warfarin effects. If major bleeding occurs, fresh frozen plasma may be given.

• When converting to warfarin from heparin, give both drugs concomitantly for 4 to 5 days until therapeutic effect of warfarin occurs.

Adverse reactions

GI: nausea, vomiting, diarrhea, abdominal cramps, stomatitis, anorexia

GU: hematuria

Hematologic: eosinophilia, bleeding, hemorrhage, agranulocytosis, leukopenia

Hepatic: hepatitis

Skin: rash, dermatitis, urticaria, pruritus, alopecia, dermal necrosis

Other: fever, "purple toes" syndrome (bilateral painful, purple lesions on toes and sides of feet), hypersensitivity reaction

Interactions

Drug-drug. Abciximab, acetaminophen (chronic use), androgens, aspirin, capecitabine, cefamandole, cefoperazone, cefotetan, chloral hydrate, chloramphenicol, clopidogrel, disulfiram, eptifibatide, fluconazole, fluoroquinolones, itraconazole, metronidazole (including vaginal use), nonsteroidal anti-inflammatory drugs, plicamycin, quinidine, quinine, sulfonamides, thrombolytics, ticlopidine, tirofiban, valproic acid, zafirlukast: increased response to warfarin, greater risk of bleeding

Barbiturates, hormonal contraceptives containing estrogen: decreased anticoagulant effect

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, INR: increased values

Partial thromboplastin time, PT: prolonged

Drug-food. Vitamin K-rich foods (large amounts): antagonism of anticoagulant effect

Drug-herbs. Angelica: prolonged PT Anise, arnica, asafetida, bromelain, chamomile, clove, danshen, devil's claw, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, ginseng, horse chestnut, licorice, meadowsweet, motherwort, onion, papain, parsley, passionflower, quassia, red clover, Reishi mushroom, rue, sweet clover, turmeric, white willow, others: increased risk of bleeding

Coenzyme Q10, green tea, St. John's wort: decreased anticoagulant effect

Drug-behaviors. Alcohol use: enhanced warfarin activity

Patient monitoring

• Monitor PT, INR, and liver function tests.

• Watch for signs and symptoms of bleeding and hepatitis.

Patient teaching

☞ Explain therapy to patient. Stress importance of adhering to schedule for laboratory tests.

☞ Instruct patient to promptly report unusual bleeding or bruising.

• Caution patient to consult prescriber before taking over-the-counter preparations or herbs.

• Advise patient to inform all other health care providers (including dentist) that he is taking warfarin.

• Tell patient not to vary his intake of foods high in vitamin K (such as leafy green vegetables, fish, pork, green tea, and tomatoes), to avoid alterations in drug's anticoagulant effect.

☞ Instruct females of childbearing age to report pregnancy immediately.

• Stress importance of avoiding contact sports and other activities that could cause injury and bleeding.

• Caution patient to avoid alcohol during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.

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