What is the recommended dose of apixaban (apixaban) to start when switching a patient with normal renal function and an International Normalized Ratio (INR) within the therapeutic range of 2-3 on warfarin (warfarin)?

Switching from Warfarin to Apixaban: Dosing When INR is 2-3

When switching from warfarin to apixaban with an INR in the therapeutic range of 2-3, discontinue warfarin and start apixaban when the INR falls below 2.0. 1

Timing of the Switch

• Stop warfarin and begin apixaban when the INR drops below 2.0, as recommended by the FDA label and major guidelines 1, 2
• Do not start apixaban while the INR remains between 2-3, as this creates overlapping anticoagulation and increases bleeding risk 1
• Monitor the INR every 1-2 days after stopping warfarin until it falls below 2.0, then initiate apixaban 1

Determining the Correct Apixaban Dose

The apixaban dose depends on whether the patient meets dose-reduction criteria, not on renal function alone:

Standard Dose: 5 mg Twice Daily

Use 5 mg twice daily for patients with 0 or 1 of the following criteria: 1, 2, 3

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

Reduced Dose: 2.5 mg Twice Daily

Use 2.5 mg twice daily only when the patient meets at least 2 of the 3 criteria listed above 1, 2, 3

Critical Dosing Pitfalls to Avoid

• The most common prescribing error is reducing the dose based on a single criterion (such as age >80 alone or renal impairment alone), when 2 criteria are required 3, 4
• Studies show that 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing, often driven by clinician concern about renal function or bleeding risk when formal criteria are not met 3
• Do not reduce the dose based solely on creatinine clearance unless the patient also meets another dose-reduction criterion 2, 3, 5
• Moderate renal impairment (CrCl 30-50 mL/min) alone does not mandate dose reduction to 2.5 mg twice daily 2, 3, 5

Renal Function Considerations

While renal function alone doesn't determine the dose, it's important to assess:

• Calculate creatinine clearance using the Cockcroft-Gault equation (not eGFR), as this was used in pivotal trials 2, 3, 5
• For CrCl >25 mL/min: Use the standard dosing algorithm based on the 3 criteria above 2, 5
• For CrCl 15-29 mL/min (severe renal impairment): Still use 5 mg twice daily unless ≥2 dose-reduction criteria are met 5, 4
• Apixaban has only 27% renal clearance, making it safer in renal impairment compared to other DOACs like dabigatran (80% renal) or rivaroxaban (66% renal) 3, 5, 4

Practical Transition Protocol

1. Stop warfarin immediately when the decision to switch is made 1
2. Check INR every 1-2 days until it falls below 2.0 1
3. Start apixaban at the appropriate dose (5 mg or 2.5 mg twice daily based on criteria) when INR <2.0 1
4. No bridging anticoagulation is needed during this transition, as the patient remains therapeutically anticoagulated with warfarin until the INR drops 1
5. Reassess renal function at least annually, or every 3-6 months if CrCl <60 mL/min 2, 3, 5

Why This Approach Matters

• Starting apixaban while the INR is still 2-3 creates excessive anticoagulation, as apixaban itself affects the INR and can falsely elevate it 1
• The FDA label explicitly states to wait until INR <2.0 to avoid this overlap 1
• This approach avoids both bleeding risk from over-anticoagulation and thrombotic risk from under-anticoagulation 1