Warfarin Dose Adjustment Based on INR Levels
Warfarin dosing should be adjusted based on INR values with the goal of maintaining a therapeutic INR range of 2.0-3.0 for most indications, with dose adjustments of 10-20% when INR values fall outside this range. 1, 2
Initial Dosing Considerations
- Start with 2-5 mg daily (lower doses for elderly, debilitated patients, or those with genetic variations in CYP2C9 and VKORC1 enzymes) 2
- Avoid loading doses as they increase risk of hemorrhagic complications without providing more rapid protection 2, 3
- Most patients are maintained on 2-10 mg daily 2
INR Monitoring Schedule
- Monitor INR daily after initial dose until stable in therapeutic range 2
- Once stable, check INR:
Dose Adjustment Algorithm Based on INR Values
For Non-Therapeutic INR Without Bleeding:
| INR Value | Recommended Action |
|---|---|
| < 2.0 | Increase weekly dose by 10-20% [1] |
| 2.0-3.0 | No change (therapeutic range for most indications) [2] |
| > 3.0 but < 4.0 | Decrease weekly dose by 10% [1] |
| 4.0-9.0 without bleeding | Hold 1-2 doses, monitor INR more frequently, resume at lower dose (10-20% reduction) when INR therapeutic [1,2] |
| > 9.0 without bleeding | Hold warfarin, administer oral vitamin K 2.5-5 mg, monitor INR daily, resume at lower dose when therapeutic [1] |
For Elevated INR With Bleeding:
- For life-threatening bleeding: Hold warfarin, administer vitamin K 5-10 mg via slow IV infusion and 4-factor prothrombin complex concentrate (PCC) at 25 U/kg 1
- For non-life-threatening major bleeding: Hold warfarin, consider vitamin K 1-2 mg orally 4
Special Considerations
- Recheck INR within 24 hours after any intervention and check daily until therapeutic range is reached and sustained for 2 consecutive days 1
- When resuming warfarin after holding for high INR, reduce dose by 10-20% 1
- Avoid high doses of vitamin K (>10 mg) as they may cause warfarin resistance for up to a week 1
- An increase in INR > 0.4 units correlates highly (81%) with the need to decrease the warfarin dose 5
- Fixed low-dose warfarin regimens (e.g., 1 mg daily) are associated with dangerous INR prolongation and should be avoided 6
Factors Affecting INR Response
- Medications: Antibiotics, steroids, and chemotherapeutic agents can significantly alter INR values 1, 7
- Diet: Vitamin K intake significantly affects warfarin response (dark green vegetables, oils) 1
- Age: Elderly patients may require lower maintenance doses 2
- Comorbidities: Liver disease affects warfarin metabolism 1
Pitfalls to Avoid
- Excessive dose adjustments for minor INR fluctuations
- Inadequate monitoring frequency after dose changes
- Failure to consider drug-drug and drug-food interactions
- Using loading doses that increase bleeding risk
- Extending INR monitoring intervals too quickly before stability is confirmed
Individualized warfarin dosing guided by algorithms has been shown to improve time in therapeutic range and reduce excessive anticoagulation events compared to fixed dosing approaches 8.