Warfarin Starting Dose Recommendations
The recommended starting dose of warfarin is 2 to 5 mg daily for most patients, with dosage adjustments based on the results of PT/INR determinations. 1
Standard Initial Dosing
- The American College of Cardiology recommends starting with 5 mg daily for most patients, which typically produces a satisfactory anticoagulant effect within 4-6 days 2
- This approach avoids the risks associated with higher loading doses while still achieving therapeutic anticoagulation in a reasonable timeframe 3
- Initial warfarin therapy should be individualized according to patient sensitivity to the drug as indicated by PT/INR monitoring 1
Special Populations Requiring Lower Initial Doses
- For elderly, debilitated patients, or those at increased risk of bleeding, a lower starting dose of 2-4 mg daily is recommended 2, 1
- Patients with certain genetic variations in CYP2C9 and VKORC1 enzymes may require lower initial doses 1
- Patients who may exhibit greater than expected PT/INR responses to warfarin should also receive lower initial doses 1
Higher Initial Dosing Considerations
- Some protocols suggest starting with warfarin 10 mg daily for the first 2 days in otherwise healthy outpatients, then adjusting based on INR measurements 4
- However, research has shown that a 10-mg loading dose is unlikely to be more effective than a 5-mg loading dose in achieving a therapeutic INR by day 4 or 5 of therapy 5
- Higher loading doses may increase the incidence of hemorrhagic complications without offering more rapid protection against thrombi formation 1, 6
Monitoring Schedule
- Check INR daily until the therapeutic range has been reached and sustained for 2 consecutive days 2, 4
- Then monitor 2-3 times weekly for 1-2 weeks, and subsequently reduce frequency according to stability of results 2
- Once the INR becomes stable, testing can be reduced to intervals as long as 4 weeks 2
Concurrent Heparin Therapy
- When rapid anticoagulation is required, heparin should be given concurrently with warfarin for at least 4 days 2
- Only discontinue heparin when the INR has been in the therapeutic range for at least 2 consecutive days 4
Common Pitfalls and Caveats
- Avoid large loading doses that can raise the INR excessively and potentially create a transient hypercoagulable state 3, 6
- Unexpected fluctuations in dose-response may occur due to changes in diet, concurrent medications, poor compliance, or alcohol consumption 2
- The safety and effectiveness of warfarin therapy depends critically on maintaining the INR within the therapeutic range 2
- A disproportionate number of thromboembolic and bleeding events occur when the INR is outside the therapeutic range 2