Warfarin

Indications

• • preventing thrombosis and embolism

  • atrial fibrillation

    • presence of artificial heart valves

  • deep venous thrombosis

  • pulmonary embolism

• antiphospholipid syndrome

Administration/Absorption

Distribution

Mechanism

• vitamin K antagonist

  • • inhibits vitamin K epoxide reductase

      • enzyme that recycles oxidized vitamin K to its reduced form after it has participated in the carboxylation of several blood coagulation proteins

        • calcium-dependent clotting factors

          • II, VII, IX and X

        • regulatory factors

          • protein C, protein S, and protein Z

• • may promote clot formation temporarily

    • when warfarin is loaded rapidly at greater than 5 mg per day, it is beneficial to co-administer heparin for four to five days

Excretion

• • duration of action of a single dose of racemic warfarin is 2 to 5 days

Side effects

Interactions

• • commonly-used antibiotics, such as metronidazole or the macrolides

    • reduce metabolism

• broad-spectrum antibiotics

  • • reduce gut flora production of vitamin K

• • excessive alcohol

  • herbs and spices

    • ginger, garlic, ginseng, Ginkgo biloba, St. John's Wort

• cranberry juice

• • erythromycin (same breakdown enzyme)

Contraindications

• • peptic ulcer

  • severe hypertension