Warfarin Dosing and Monitoring Protocol
The typical initial dose of warfarin is 5 mg daily for most patients, with subsequent dosing based on INR monitoring, while lower starting doses (2-4 mg) should be used for elderly, frail patients, or those with increased bleeding risk. 1
Initial Dosing Strategy
Standard Initial Dosing
- For outpatients who are sufficiently healthy: 10 mg daily for the first 2 days, then adjust based on INR 2, 1
- For hospitalized patients, elderly, or those at higher bleeding risk: 5 mg daily 2, 1, 3
- For very elderly or patients with potential for enhanced warfarin sensitivity: 2-4 mg daily 3, 4
Patient-Specific Considerations for Lower Initial Doses (2-4 mg)
- Advanced age (>65 years)
- Frailty
- Renal insufficiency
- Liver disease
- Genetic variations in CYP2C9 and VKORC1 enzymes
- Malnutrition
- Concomitant medications that potentiate warfarin effects 1, 3
Monitoring Protocol
Initial Phase
- Check INR daily until therapeutic range is reached and sustained for 2 consecutive days 2
- Then monitor 2-3 times weekly for 1-2 weeks 2, 4
- Then reduce frequency based on stability of results 2, 1
Maintenance Phase
- Once stable, gradually extend monitoring intervals
- Maximum interval between INR tests should not exceed 4-6 weeks 2, 4
- Resume frequent monitoring when dose adjustments are required 2
Target INR Range and Dose Adjustments
Standard Target Range
- For most indications (atrial fibrillation, VTE): INR 2.0-3.0 1
- For mechanical heart valves: INR 2.5-3.5 3
Dose Adjustment Algorithm
| INR | Dose Adjustment |
|---|---|
| <1.5 | Increase weekly dose by 15% |
| 1.6-1.9 | Increase weekly dose by 10% |
| 2.0-3.0 | No change (therapeutic range) |
| 3.0-3.9 | Decrease weekly dose by 10% |
| 4.0-4.9 | Hold 1 dose, then restart with 10% dose reduction |
| ≥5.0 | Hold until INR is 2-3, then restart with 15% dose reduction [1] |
Special Considerations
Overlap with Parenteral Anticoagulation
- Continue parenteral anticoagulation (heparin) until INR has been in therapeutic range for at least 2 consecutive days 2, 1
- This typically requires 4-5 days of overlap 2
Maintenance Dosing
- Most patients are maintained on 2-10 mg daily 1, 3
- Dose changes should alter the total weekly dose by 5-20% 4
Managing Elevated INR
- For INR 5-9 without bleeding: Omit 1-2 doses and consider oral vitamin K1 (1-2.5 mg) 2
- For INR >9 without significant bleeding: Give oral vitamin K1 (3-5 mg) 2
- For serious bleeding: Administer vitamin K1 by slow IV infusion (10 mg) plus fresh plasma or prothrombin complex concentrate 2
Common Pitfalls and Caveats
Loading dose caution: Higher loading doses (10 mg) may lead to excessive anticoagulation in sensitive individuals, with 36% of patients experiencing INR >3.0 at 60 hours 5
Drug interactions: Many medications can potentiate or inhibit warfarin's effect, requiring close monitoring when starting or stopping other medications 1
Diet considerations: Fluctuations in vitamin K intake can affect INR stability 2
Missed doses: Patients should take missed doses on the same day if remembered, but should not double the next dose 3
Bleeding risk: Risk increases exponentially with INR values >5.0 and is higher in elderly patients, those with prior stroke or GI bleeding, and those with renal insufficiency 2
Monitoring frequency: Inadequate monitoring is a major cause of complications; never extend intervals beyond 4-6 weeks even in stable patients 4
By following this structured approach to warfarin dosing and monitoring, clinicians can optimize anticoagulation efficacy while minimizing bleeding risks.