When switching from apixaban to warfarin, is a loading dose of warfarin required?

Switching from Apixaban to Warfarin: No Loading Dose Required

When transitioning from apixaban to warfarin, do not use a loading dose of warfarin—start warfarin at the anticipated maintenance dose (typically 5 mg or less in older adults) while continuing apixaban, then discontinue apixaban once the INR reaches therapeutic range. 1

Recommended Transition Strategy

The FDA-approved approach requires overlapping therapy rather than loading: 1

• Discontinue apixaban and simultaneously start both a parenteral anticoagulant (such as heparin or LMWH) and warfarin at the time the next dose of apixaban would have been taken 1
• Continue the parenteral anticoagulant until the INR reaches an acceptable therapeutic range (2.0-3.0) 1
• Start warfarin at the expected maintenance dose, not a loading dose 2

Why No Loading Dose?

Loading doses of warfarin are generally not recommended in modern practice, particularly in older adults with atrial fibrillation: 2

• Warfarin should be initiated at a dose approximating the average maintenance dose, usually less than 5 mg daily in older people 2
• Loading doses can cause excessive anticoagulation and create a transient prothrombotic state due to rapid depletion of protein C before depletion of procoagulant factors 3
• The European Heart Rhythm Association guideline emphasizes that various factors favor using a low starting dose (5 mg or even 2 mg daily), including older age, frailty, and renal insufficiency 2

Practical Dosing Considerations

Initial warfarin dosing should be conservative: 2, 4

• Start with 5 mg daily (or 2-4 mg in the very elderly) 2, 4
• With a 5 mg initial dose, the INR will not rise appreciably in the first 24 hours except in rare patients who ultimately require very small daily doses (0.5-2.0 mg) 4
• Automated dosing calculators are available but no strong recommendation exists for routinely using either 5 mg or 10 mg starting strategies in AF patients 2

Critical Caveat About Apixaban's Effect on INR

Apixaban affects INR measurements, making initial INR values unreliable for warfarin dosing during the transition: 1

• The INR measurements during the overlap period may not accurately reflect warfarin's anticoagulant effect 1
• This is why the parenteral anticoagulant bridge is necessary—to maintain therapeutic anticoagulation while warfarin reaches steady state 1
• Only discontinue the parenteral anticoagulant after the INR has been in therapeutic range for at least two measurements taken more than 24 hours apart 2

Monitoring Requirements

Frequent monitoring is essential during the transition: 2, 4

• Monitor INR daily until stable, with therapeutic INR usually achieved in 5-7 days 2
• Then monitor 2-3 times weekly for 1-2 weeks, then weekly for 1 month, and monthly thereafter 2
• More frequent monitoring may be required in older adults due to increased risk of fluctuations 2