The major oral anticoagulant used in the United States is the coumarin compound warfarin.
Warfarin is absorbed rapidly and almost completely when it’s tak-en orally. It binds extensively to plasma albumin and is metabo-lized in the liver and excreted in urine. Although warfarin is ab-sorbed quickly, its effects don’t occur for about 48 hours, with the full effect taking 3 to 4 days.
Because warfarin is highly plasma-protein-bound and is metab-olized by the liver, administration of warfarin with other medica-tions may alter the amount of warfarin in the body. This may in-crease the risk of bleeding or clotting, depending upon the med-ications administered.
Oral anticoagulants alter the ability of the liver to synthesize vita-min K–dependent clotting factors, including prothrombin and fac-tors VII, IX, and X. However, clotting factors already in the blood-stream continue to coagulate blood until they become depleted, so anticoagulation doesn’t begin immediately. (See Monitoringwarfarin levels.)
Oral anticoagulants are prescribed to treat or prevent thromboem-bolism. Patients with this disorder begin taking the medication while still receiving heparin. However, outpatients at high risk for thromboembolism may begin oral anticoagulants without first re-ceiving heparin.
Oral anticoagulants are also the drugs of choice to prevent DVT and for patients with prosthetic heart valves or diseased mitral valves. To decrease the risk of arterial clotting, oral anticoagulants are sometimes combined with an antiplatelet drug, such as as-pirin, clopidogrel, or dipyridamole.
Many patients who take oral anticoagulants also receive other drugs, placing them at risk for serious drug interactions.
· Many drugs, such as highly protein-bound medications, increase the effects of warfarin, resulting in an increased risk of bleeding. Examples include acetaminophen, allopurinol, amiodarone, cephalosporins, cimetidine, ciprofloxacin, clofibrate, danazol, dia-zoxide, disulfiram, erythromycin, fluoroquinolones, glucagon, he-parin, ibuprofen, isoniazid, ketoprofen, methylthiouracil, metron-idazole, miconazole, neomycin, propafenone, propylthiouracil, quinidine, streptokinase, sulfonamides, tamoxifen, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, and vitamin E.
· Drugs metabolized by the liver may increase or decrease the ef-fectiveness of warfarin. Examples include barbiturates, carba-mazepine, corticosteroids, corticotropin, mercaptopurine, naf-cillin, hormonal contraceptives containing estrogen, rifampin, spironolactone, sucralfate, and trazodone.
· The risk of phenytoin toxicity increases when phenytoin is tak-en with warfarin, and phenytoin may increase or decrease the ef-fects of warfarin.
Other interactions include the following:
§ A diet high in vitamin K reduces the effectiveness of warfarin.
§ Chronic alcohol abuse increases the patient’s risk of clotting while taking warfarin. Acute alcohol intoxication increases the risk of bleeding.
§ Vitamin K and fresh frozen plasma reduce the effects of war-farin. (See Adverse reactions to oral anticoagulants.)