What is the initial dose of warfarin (International Normalized Ratio (INR) anticoagulant) for initiation of therapy?

Initial Warfarin Dosing for Anticoagulation Therapy

For most patients, warfarin therapy should be initiated with a dose of 5 mg daily for the first 2-3 days, followed by INR-based dosing adjustments. 1

Initial Dosing Recommendations

• Standard initial dosing:

  • 5 mg daily for most patients 1, 2
  • 10 mg daily for the first 2 days may be appropriate for healthy outpatients (shortens time to therapeutic INR to 4.2 vs 5.6 days with 5 mg dosing) 1
  • 2-4 mg daily for elderly, debilitated patients, or those at higher bleeding risk 2, 3

• Patient-specific considerations affecting initial dose:

  • Lower doses (2-4 mg) recommended for:
    • Elderly patients
    • Frail patients
    • Patients with renal insufficiency
    • Patients with genetic variations in CYP2C9 and VKORC1 enzymes
    • Patients likely to exhibit greater than expected PT/INR responses 4, 2

Monitoring Protocol

• Monitor INR frequently after initiation:

  • 2-3 times weekly for 1-2 weeks 1
  • Then less frequently based on stability of results
  • Maximum interval between INR tests should not exceed 4-6 weeks once stable 1, 3

• Target INR range:

  • 2.0-3.0 for most indications (atrial fibrillation, venous thromboembolism) 4
  • Higher targets (2.5-3.5) for specific indications like mechanical heart valves 2

Dose Adjustment Algorithm

When INR results are available, adjust dosing according to this schedule 4:

INR	Dose adjustment per week
<1.5	Increase by 15%
1.6-1.9	Increase by 10%
2.0-2.9	Unchanged
3.0-3.9	Decrease by 10%
4.0-4.9	Hold 1 dose, then restart with dose decrease by 10%
≥5.0	Hold until INR is 2-3, then restart with dose decrease by 15%

Important Clinical Considerations

• Parenteral anticoagulation overlap: When immediate anticoagulation is needed, start warfarin concurrently with parenteral anticoagulation (heparin, LMWH) and continue the parenteral agent until INR is therapeutic for at least 2 consecutive days 1

• Loading doses: High loading doses (>5 mg) may increase hemorrhagic complications without offering more rapid protection against thrombi formation 2

• Pharmacogenetic testing: While genetic variations in CYP2C9 and VKORC1 affect warfarin metabolism, routine genetic testing before initiation is not recommended 1

• Common pitfalls to avoid:

  • Using excessive loading doses
  • Failing to consider patient-specific factors (age, comorbidities)
  • Inadequate monitoring frequency during initiation
  • Overlooking drug-drug interactions that can potentiate or inhibit warfarin's effect 1, 2

• Maintenance dosing: Most patients are maintained on 2-10 mg daily, with dosage individualized based on INR response 2

The European Heart Rhythm Association guidelines note that while 10 mg initiation may help VTE patients reach therapeutic INR faster, AF patients are generally older and more frail, making a lower starting dose more appropriate in many cases 4. The FDA label similarly recommends starting with 2-5 mg daily with adjustments based on INR results 2.