What is the proper dosing of warfarin (International Normalized Ratio (INR) anticoagulant)?

Warfarin Dosing Guidelines

The recommended initial warfarin dosing is 5 mg daily for most patients, with daily INR monitoring until the therapeutic range is reached and maintained for 2 consecutive days, followed by less frequent monitoring as stability is achieved. 1, 2

Initial Dosing Strategy

• For most patients, start with 5 mg daily, which typically produces a satisfactory anticoagulant effect within 4-6 days 1
• For patients who are elderly, debilitated, or at increased risk of bleeding, use lower starting doses of 2-4 mg daily 1, 2
• For younger (under 60 years), otherwise healthy patients, a higher initial dose of 10 mg daily for the first 2 days may be considered, which can result in shorter time to therapeutic INR (4.2 vs 5.6 days) 3, 4
• When rapid anticoagulation is required, heparin should be given concurrently with warfarin for at least 4 days 1
• Avoid loading doses as they may increase the risk of hemorrhagic complications without offering more rapid protection against thrombi formation 2, 4

INR Monitoring Schedule

• Check INR daily until the therapeutic range has been reached and sustained for 2 consecutive days 1
• Then monitor 2-3 times weekly for 1-2 weeks 1
• Subsequently reduce frequency according to stability of results 1
• Once the INR becomes stable, testing can be reduced to intervals as long as 4 weeks 1
• Resume frequent monitoring when dose adjustments are required 1

Target INR Ranges by Indication

• Venous thromboembolism (DVT/PE): Target INR 2.5 (range 2.0-3.0) 2
• Non-valvular atrial fibrillation: Target INR 2.5 (range 2.0-3.0) 2
• Mechanical heart valves:
  • St. Jude bileaflet valve in aortic position: Target INR 2.5 (range 2.0-3.0) 2
  • Tilting disk valves and bileaflet valves in mitral position: Target INR 3.0 (range 2.5-3.5) 2
  • Caged ball or caged disk valves: Target INR 3.0 (range 2.5-3.5) plus aspirin 75-100 mg/day 2
• Post-myocardial infarction: Target INR 2.5 (range 2.0-3.0) with aspirin 2

Maintenance Dosing

• Most patients are satisfactorily maintained at a dose of 2-10 mg daily 2
• Adjust dosage based on the patient's INR response 2
• When dose adjustments are required, change the total weekly dose by 5-20% 4
• Flexibility of dosage is provided by breaking scored tablets in half 2

Special Populations

• Elderly patients (≥60 years) exhibit greater than expected INR response to warfarin and generally require lower doses 2
• Asian patients may require lower initiation and maintenance doses 2
• Patients with certain genetic variations in CYP2C9 and VKORC1 enzymes may require lower doses 2
• For pregnant patients with mechanical heart valves:
  • If warfarin dose ≤5 mg/day, continuation throughout pregnancy may be reasonable 1
  • If warfarin dose >5 mg/day, consider dose-adjusted LMWH during first trimester 1

Common Pitfalls and Caveats

• Unexpected fluctuations in dose-response may occur due to changes in diet, concurrent medications, poor compliance, or alcohol consumption 1
• The safety and effectiveness of warfarin therapy depends critically on maintaining the INR within the therapeutic range 1
• A disproportionate number of thromboembolic and bleeding events occur when the INR is outside the therapeutic range 1
• Risk of bleeding increases exponentially with INR and becomes clinically unacceptable once the INR exceeds 5.0 5
• If a patient misses a dose, they should take it as soon as possible on the same day but should not double the next dose to make up for missed doses 2
• When switching between warfarin products, additional INR testing is recommended 2

Managing Elevated INR

• For non-bleeding patients with INR >9, low-dose vitamin K1 (e.g., 2.5 mg orally) may be given 4
• Patients with excessive INR and clinically important bleeding require clotting factors (e.g., fresh-frozen plasma) as well as vitamin K1 4