Warfarin

Trade names

COUMADIN, JANTOVEN

Actions

• Vitamin K antagonist

Route of Administration

Oral

Bioavailability

79-100%

Plasma protein binding

99%

Time to peak plasma concentration

Variable

Half-life

20–60 h

Duration of action

48–96 h

Metabolism

Hepatic

Enzymes involved

• CYP2C9
• CYP3A4
• CYP1A1
• CYP1A2

Elimination

Renal 92% (excretion of inactive metabolites)

Interactions

Drugs that inhibit or induce CYP2C9, CYP3A4, CYP1A2

Recommended dose

Individualized. Dose is adjusted by monitoring the INR.

In patients with atrial fibrillation as well as in patients with pulmonary embolism or DVT the recommended INR range is 2.0 - 3.0

In patients with mechanical valves the recommended INR range is usually 2.5 - 3.5

Renal impairment

No dose adjustment is necessary.

Discontinuation before invasive procedures

Warfarin should be stopped 5 days prior to surgery. The thromboembolic risk should be individually assessed. In patients with low risk no bridging with LMWH is required. In patients with moderate risk, bridging should be considered. In patients with high risk, bridging is recommended.

Start LMWH or unfractionated heparin in therapeutic doses as soon as the INR is under the therapeutic lower limit.

Discontinue LMWH 24 hours before the procedure. If UFH is used, discontinue 4-6 hours before the procedure.

The efficacy of bridging remains unclear and some studies suggest it carries a higher bleeding risk.