What is the protocol for transitioning a patient from Coumadin (warfarin) to Eliquis (apixaban), considering factors such as age, weight, renal function, and history of bleeding complications?

Transitioning from Coumadin to Eliquis

Discontinue warfarin and start apixaban when the INR falls below 2.0. 1

Step-by-Step Transition Protocol

1. Stop Warfarin and Monitor INR

• Discontinue warfarin immediately and check INR daily until it drops below 2.0 1
• Do not initiate apixaban while INR remains ≥2.0, as this increases bleeding risk during the overlap period 1
• The waiting period typically ranges from 2-5 days depending on the patient's warfarin dose and individual metabolism 2

2. Initiate Apixaban at Appropriate Dose

Standard dose: 5 mg twice daily for most patients 1

Reduced dose: 2.5 mg twice daily if the patient has at least 2 of the following 3 criteria: 3, 1

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

3. Renal Function Assessment

Before initiating apixaban, calculate creatinine clearance using the Cockcroft-Gault method: 3

• CrCl >50 mL/min: Standard dosing (5 mg BID or 2.5 mg BID based on criteria above) 3
• CrCl 30-50 mL/min: Standard dosing applies, but monitor closely 3
• CrCl 15-30 mL/min: Use with extreme caution; apixaban 5 mg BID with dose reduction to 2.5 mg BID if patient is ≥80 years or body weight ≤60 kg 3
• CrCl <15 mL/min or dialysis: Not recommended due to lack of clinical trial data 3

Reassess renal function at least annually and whenever clinically indicated (acute illness, medication changes, weight fluctuations) 3

4. Special Considerations for High-Risk Patients

Elderly and Frail Patients

• Patients ≥75 years have increased bleeding risk even at therapeutic anticoagulation levels 4
• Frail patients with low BMI (<18.5) may have reduced protein binding, increasing free drug concentration and bleeding risk 4
• Monitor more frequently during the first month after transition in elderly/frail patients 4

Patients with History of Bleeding

• Consider whether the bleeding risk outweighs stroke prevention benefit before transitioning 3
• The 2.5 mg BID dose may be appropriate even if only one criterion is met in patients with significant bleeding history, though this is off-label 3

5. Drug Interaction Management

Reduce apixaban dose by 50% when coadministered with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 1

In patients already taking 2.5 mg BID, avoid coadministration with these inhibitors 1

Common interacting medications to review:

• Antiplatelet agents (aspirin, clopidogrel) significantly increase bleeding risk 3
• NSAIDs increase bleeding risk and should be avoided or used cautiously 3

6. Timing Considerations

Do not bridge with parenteral anticoagulation during the warfarin-to-apixaban transition in most cases 1

The exception is patients at extremely high thrombotic risk (mechanical heart valves, recent stroke within 3 months), though apixaban is contraindicated with mechanical heart valves 3

7. Patient Education

Inform patients that:

• Apixaban must be taken exactly twice daily (every 12 hours) for consistent anticoagulation 1
• If a dose is missed, take it as soon as remembered on the same day, but never double the dose 1
• Unlike warfarin, no routine blood monitoring is required, but renal function must be checked periodically 3
• Apixaban has no reversal agent readily available (unlike warfarin's vitamin K), making management of major bleeding more complex 3

8. Common Pitfalls to Avoid

• Never start apixaban while INR is still ≥2.0, as the combined anticoagulant effect dramatically increases bleeding risk 1
• Do not use standard 5 mg BID dosing in patients meeting dose-reduction criteria, as this leads to excessive anticoagulation 3, 1
• Do not overlook renal function assessment—apixaban accumulates in renal impairment and requires dose adjustment or avoidance 3
• Avoid assuming bioequivalence between different warfarin formulations during the transition period, as INR may fluctuate unpredictably 5
• Do not forget to discontinue INR monitoring after transition is complete, as apixaban does not require routine coagulation testing 1

9. Post-Transition Monitoring

• No routine INR monitoring is needed once apixaban is established 1
• Reassess renal function in 3-6 months, then annually 3
• Evaluate for bleeding or thrombotic complications at follow-up visits 6
• Monitor for medication adherence, as twice-daily dosing may be challenging for some patients 1