Warfarin Dosing Regimen
For most outpatients who are otherwise healthy, start warfarin at 10 mg daily for the first 2 days, then adjust based on INR measurements, targeting an INR of 2.0-3.0. 1
Initial Dosing Strategy
Standard Outpatient Dosing
- Begin with 10 mg daily for 2 days in younger (e.g., <60 years), otherwise healthy outpatients 1
- This approach achieves therapeutic INR faster (mean 4.2 vs 5.6 days) with approximately 86% of patients reaching therapeutic range by day 5, compared to only 45% with 5 mg initial dosing 2
- After the first 2 days, adjust the dose based on INR measurements rather than continuing a fixed loading dose 1
Modified Dosing for Higher-Risk Patients
- Use 5 mg daily (or 2-4 mg) for elderly patients, those who are debilitated, or at increased bleeding risk 3, 4
- The 5 mg starting dose typically produces satisfactory anticoagulation within 4-6 days 3
- For very elderly patients, consider starting at 2-4 mg daily 3
Concurrent Heparin Therapy
- Start warfarin on day 1 or 2 of heparin (UFH, LMWH, or fondaparinux) therapy 1
- Continue heparin for at least 5 days AND until INR is 2.0-3.0 for 2 consecutive days 1
- This overlap mitigates the theoretical transient hypercoagulable state from rapid protein C depletion that occurs with 10 mg loading 2
Target INR Range
Standard Therapeutic Range
- Target INR of 2.5 (range 2.0-3.0) for most indications 1, 5
- This moderate-intensity anticoagulation is as effective as higher intensity (INR 3.0-4.5) but with significantly less bleeding risk 1
Specific Indications
- Venous thromboembolism (DVT/PE): INR 2.0-3.0 1, 5
- Atrial fibrillation: INR 2.0-3.0 5
- Mechanical heart valves: INR 2.5-3.5 for most valve types; INR 2.0-3.0 may suffice for bileaflet valves in aortic position 5, 6
INR Monitoring Schedule
Initial Phase (First 2 Weeks)
- Check INR daily until therapeutic range (2.0-3.0) is reached and sustained for 2 consecutive days 3, 2
- Then monitor 2-3 times weekly for 1-2 weeks 3, 2
Maintenance Phase
- Once INR stabilizes, progressively extend monitoring intervals 1, 3
- For patients with consistently stable INRs, testing frequency can be extended up to 12 weeks rather than the traditional 4 weeks 1
- The appropriate interval depends on prior stability duration and foreseeable changes in medications or clinical status 1
Management of Single Out-of-Range INR
- For a single INR 0.5 below or above therapeutic range (e.g., INR 1.5-3.5 when target is 2.0-3.0), continue the current dose and recheck INR in 1-2 weeks 1
- Do not routinely adjust doses for isolated minor deviations 1
- Do not routinely bridge with heparin for single subtherapeutic INR values 1
Important Clinical Considerations
Pharmacogenetic Testing
- Do not routinely use pharmacogenetic testing to guide warfarin dosing 1
- This is a strong recommendation (Grade 1B) despite the theoretical appeal 1
Factors Affecting Dose Requirements
- Age significantly affects dosing, with older patients requiring lower maintenance doses 1, 2
- Drug interactions are common and can dramatically alter warfarin response 3
- Dietary vitamin K intake, hepatic dysfunction, and hypermetabolic states influence dosing 7
- Poor compliance and alcohol consumption cause unexpected fluctuations 3
Common Pitfalls to Avoid
- Avoid excessive loading doses that raise INR too rapidly 4
- The 10 mg initial dose does not appreciably raise INR in the first 24 hours except in rare patients who ultimately require very small maintenance doses (0.5-2.0 mg daily) 4
- A disproportionate number of thromboembolic and bleeding events occur when INR is outside therapeutic range 3
- High-intensity warfarin (INR 3.0-4.5) for stroke prevention in arterial disease is dangerous, with unacceptable bleeding rates including intracranial hemorrhage 1