Warfarin Dose Adjustment Based on INR Levels
Adjust warfarin by 10-15% of the weekly dose based on INR values using a structured algorithm, maintaining a target INR of 2.0-3.0 for most indications, and avoid overreacting to single mildly elevated INRs in stable patients. 1, 2
Target INR Range
- The standard therapeutic target is INR 2.0-3.0 (target 2.5) for most indications including venous thromboembolism, atrial fibrillation, and most mechanical heart valves 1, 3
- Higher intensity anticoagulation (INR 2.5-3.5, target 3.0) is reserved for specific mechanical valve types (tilting disk, bileaflet valves in mitral position, caged ball/disk valves) 3
Structured Dose Adjustment Algorithm
For patients on established warfarin therapy, use the following weekly dose adjustments: 1, 2
Subtherapeutic INR
Therapeutic INR
Supratherapeutic INR Without Bleeding
- INR 3.0-3.9: Decrease weekly dose by 10% 1, 2
- INR 4.0-4.9: Hold one dose, then restart with weekly dose decreased by 10% 1, 2
- INR 5.0-9.0: Hold 1-2 doses until INR returns to 2.0-3.0, then restart with weekly dose decreased by 15% 1, 2
- INR ≥9.0 without bleeding: Give oral vitamin K 3-5 mg (expect INR reduction within 24-48 hours), then restart at reduced dose when INR is 2.0-3.0 1, 2
Life-Threatening Bleeding
- Any INR with serious bleeding: Administer prothrombin complex concentrate plus vitamin K 10 mg IV immediately 1, 2
- If prothrombin complex concentrate unavailable, use fresh frozen plasma 2
INR Monitoring Frequency
Adjust monitoring intensity based on stability and clinical context: 1, 2, 3
- Initial stabilization: Check INR daily until therapeutic for 2 consecutive days 1, 2, 3
- Early maintenance: Monitor 2-3 times weekly for 1-2 weeks after achieving therapeutic range 1, 2
- First month: Monitor weekly 1, 2
- Stable patients: Monitor every 2-4 weeks, with intervals potentially extended up to 12 weeks in consistently stable patients 1, 3
- After dose changes or clinical events: Resume frequent monitoring after any dose adjustment, intercurrent illness, medication changes, or minor bleeding 1, 2
Critical Pitfalls to Avoid
Do not overreact to minor INR fluctuations in previously stable patients. 1, 2, 4
- For a single INR ≤0.5 below therapeutic range with previously stable values, continue current dose and retest within 1-2 weeks 1
- For isolated, asymptomatic INR values of 3.2-3.4, maintaining the same dose is safe and results in better INR control than dose reduction 4
- Avoid warfarin dose reductions >20% for mildly elevated INRs, as this frequently causes subtherapeutic INR 4
Avoid high-dose vitamin K for non-urgent INR reversal. 1, 2
- High-dose vitamin K (≥10 mg oral) may cause warfarin resistance for up to one week 1, 2
- Oral vitamin K is preferred over parenteral routes for non-urgent reversal due to predictable effectiveness and safety 1
Do not use routine heparin bridging for single subtherapeutic INR in stable patients. 1, 2
Special Considerations
Computer-guided dosing algorithms may improve INR control, particularly for inexperienced providers. 5, 1, 2, 6
- Computerized warfarin adjustment achieves significantly better control when intensive therapy (INR 3.0-4.5) is required 5
- Application of dosing calculators can shorten time to first therapeutic INR and improve time in therapeutic range 6
Drug interactions require resumed frequent INR monitoring. 1, 2
- NSAIDs, antibiotics (especially fluoroquinolones, metronidazole), and antifungals significantly affect warfarin response 1, 2
- Corticosteroids like prednisone typically increase INR, though preemptive dose reduction may cause more subtherapeutic INRs than reactive monitoring 7
Maintain consistent vitamin K intake, as dietary fluctuations affect warfarin response. 1, 2
Initial dosing should start at 2-5 mg daily (lower doses for elderly/debilitated patients), avoiding loading doses. 3, 8