Warfarin Dose Adjustment Based on INR Levels
Warfarin dosing should be adjusted based on INR values following a structured algorithm, with dose increases for subtherapeutic INRs and dose reductions or temporary holds for supratherapeutic INRs, while maintaining the target INR of 2.0-3.0 for most indications. 1
Initial Dosing
- Start with 2-5 mg daily for most patients, avoiding large loading doses which increase hemorrhagic complications without providing faster protection against thrombi formation 2
- Lower initial doses (2-4 mg) are recommended for elderly, debilitated patients, or those with potential for greater than expected INR response 2, 3
- Monitor INR daily after initial dose until stabilization in therapeutic range, then extend monitoring intervals based on stability 2
Target INR Ranges
- Standard target INR: 2.0-3.0 for most indications including venous thromboembolism and atrial fibrillation 1, 2
- Higher target INR: 2.5-3.5 for mechanical heart valves in mitral position or caged ball/disk valves 2
- For patients with mechanical heart valves in aortic position (St. Jude Medical bileaflet valve), target INR of 2.0-3.0 is recommended 2
Maintenance Dose Adjustment Algorithm
For established warfarin therapy, adjust doses based on INR as follows:
| INR | Dose Adjustment |
|---|---|
| <1.5 | Increase by 15% per week [1] |
| 1.6-1.9 | Increase by 10% per week [1] |
| 2.0-2.9 | No change (therapeutic for most indications) [1] |
| 3.0-3.9 | Decrease by 10% per week [1] |
| 4.0-4.9 | Hold 1 dose, then restart with dose decreased by 10% per week [1] |
| ≥5.0 | Hold until INR is 2-3, then restart with dose decreased by 15% per week [1] |
Management of Subtherapeutic INR
- For a single INR ≤0.5 below therapeutic range with previously stable INRs, continue current dose and retest within 1-2 weeks 4
- For persistently low INR or high-risk patients (mechanical heart valves), consider more aggressive dose adjustments 4
- Routine heparin bridging is not recommended for patients with a single subtherapeutic INR 4
Management of Supratherapeutic INR
When INR is excessively elevated:
- For INR >4 but <5 without bleeding: Reduce dose or omit a dose, monitor more frequently, and resume at lower dose when INR returns to therapeutic range 1
- For INR ≥5 without significant bleeding: Hold warfarin temporarily, consider low-dose vitamin K1 for rapid INR correction 1
- For serious bleeding at any INR: Administer vitamin K1 plus fresh plasma or prothrombin concentrate for immediate reversal 1
Monitoring Frequency
- Daily INR monitoring after initial dose until stabilization 2
- Once stable, monitoring intervals can be extended to 1-4 weeks 2
- More frequent monitoring is needed when interacting medications are started or stopped 2
Special Considerations
- Avoid loading doses, as they increase bleeding risk without providing faster protection 3
- For elderly patients, consider lower doses and more careful monitoring 2
- Computer-guided dosing algorithms may improve INR control compared to manual regulation, particularly for inexperienced providers 1
- Patients managed by anticoagulation clinics typically spend more time in therapeutic range (56%-93%) compared to usual care (33%-64%) 2
Common Pitfalls to Avoid
- Overreacting to minor INR deviations with immediate dose changes when not necessary 4
- Using high doses of vitamin K1 (e.g., 10 mg) for INR reversal, which may lead to warfarin resistance for up to a week 1
- Doubling doses to "catch up" after missed doses 2
- Failing to account for drug interactions, dietary changes, or acute illness that may affect INR 2