Warfarin

Drugs that increase effects of Warfarin

Aspirin, Sulfonamides, Acetaminophen, Amidarone, Azole anti fungal agents, Cimetidine, Disulfiram,Trimethoprim-Sulfamethoxazole

(Generic) Warfarin

(Trade) Coumadin, Jantoven

Drugs that promote bleeding

Abciximab, Aspirin and other Salicylates, Clopidrogel, Heparins, Antimetabolites, Glucocorticoids

Drugs that decrease the effects of Warfarin

Carbamazepine, Phenobarbital, Phenytoin, Rifampin, Oral contraceptives, Vitamin K, Cholestyramine, Colestipol

Therapeutic use

Frequently used for long term prophylaxis of thrombosis. (Specific indications are (1) prevention of venous thrombosis & associated PE, (2) prevention of thromboembolism in pts with prosthetic heart valves and (3) prevention of thrombosis in pts with atrial fibrillation. It has also been used to reduce the risk of recurrent transient ischemic attacks(TIAs) and recurrent MI.)

Four major drugs likely to cause interactions

Heparin,Aspirin, Non-aspirin antiplatelet drugs, Acetaminophen

Side effects

Less serious - bleeding from gums when brushing teeth, diarrhea, n/v, heavy menstrual bleeding, easy bruising. More serious - Severe headache or stomach pain, hemorrhage, skin necrosis, red-orange urine, alopecia, urticaria.

Time course

Long half life,remains active for 2 to 5 days after dc (Although Warfarin acts quickly to inhibit clotting factor synthesis, noticeable anticoagulant effects are delayed because warfarin has no effect on clotting factors already in circulation so until the clotting factors decay, coagulation remains unaffected.Initial responses may not be evident until 8 to 12 hours after first dose and peak effects take several days to develop)

Elimination

Metabolites are excreted in the urine and feces.

Classification

Oral Anticoagulant

Contraindications

Pts with severe thrombocytopenia or uncontrolled bleeding. Pts undergoing lumbar puncture, regional anesthesia, or surgery of the eye, brain, or spinal cord. (Pts at high risk of bleeding, hemophilia, increased capillary permeability, dissecting aneurysm, GI ulcers, severe hypertension, and in women anticipating an abortion. Additionally, it is also contraindicated in the presence of vitamin K deficiency, liver disease, and alcoholism. Also during pregnancy and lactation.)

Nursing considerations

Review drug regimen, many interactions possible. Monitor for hyponatremia, activation of mania.Taper when dc.

Patient teaching

Take in the morning. Watch for signs of bleeding, (bruising for no reason,) do not stop suddenly, avoid pregnancy, breastfeeding and st johns wort. Eat small frequent meals for GI upset, report rash, mania, severe N/V, thoughts of suicide.

Labs

The effects of Warfarin are evaluated by monitoring prothrombin time (PT), (a coagulation test that is especially sensitive to alterations in Vit K dependent factors. The average pretreatment value for PT is 12 seconds. Treatment with Warfarin prolongs PT)

Antidote

Vitamin K

Correct dosage range and route

Warfarin can be taken orally or injected.Dosing normally start at 2 to 5 mg/day. Maintenance dosage range from 2 to 10 mg/day.

Pharmacologic

Warfarin is readily absorbed after oral dosing. Once in the blood, about 99% of Warfarin binds to albumin. The unbound molecules can readily cross membranes, including those of the placenta and milk producing glands. Warfarin is inactivated in the liver.

Mechanism of action

Warfarin suppresses coagulation by decreasing production of four clotting factors, namely factors VII,IX,X, and prothrombin. (These factors are known as vitamin K dependent clotting factors, because an active form of vitamin K is needed to make them. Warfarin works by inhibiting vitamin K epoxide reductase complex 1, the enzyme needed to convert vitamin K to the required active form. Because of this, Warfarin is referred to as a vitmain K antagonist.)

FDA Category

X