What is the recommended protocol for transitioning from Eliquis (apixaban) to Coumadin (warfarin)?

Transitioning from Eliquis (Apixaban) to Coumadin (Warfarin)

Start warfarin at the usual initial dose (typically 5 mg daily) while simultaneously beginning a parenteral anticoagulant (LMWH or UFH) at the time of the next scheduled apixaban dose, continue both for at least 5 days until INR ≥2.0 for at least 24 hours, then discontinue the parenteral anticoagulant. 1, 2, 3

Step-by-Step Transition Protocol

Timing and Initiation

• Discontinue apixaban and start warfarin plus parenteral anticoagulation at the exact time the next apixaban dose would have been due 1, 3
• Do not use a loading dose of warfarin—the expected maintenance dose (typically 5 mg daily, or 2.5 mg if liver disease or interacting medications are present) is safer 1, 2
• Critical principle: Apixaban affects INR measurements, making initial INR values during transition unreliable for determining appropriate warfarin dosing 3

Parenteral Bridge Options

Choose one of the following parenteral anticoagulants 1, 2:

Low Molecular Weight Heparin (LMWH):

• Dalteparin 200 units/kg subcutaneously once daily, OR
• Enoxaparin 1 mg/kg subcutaneously every 12 hours

Unfractionated Heparin (UFH):

• Intravenous: 80 units/kg bolus, then 18 units/kg/hour infusion (targeting aPTT 2-2.5× control), OR
• Subcutaneous: 333 units/kg loading dose, then 250 units/kg every 12 hours

Monitoring Requirements

• Check INR daily during the transition period 2
• Obtain baseline labs before transition: CBC, PT, aPTT, renal function, and hepatic function 1, 2
• Monitor renal function during transition, as changes affect both apixaban clearance and warfarin dosing 2

When to Stop Parenteral Anticoagulation

Both criteria must be met 2:

1. At least 5 days of overlap therapy completed, AND
2. INR ≥2.0 for at least 24 hours (target INR 2.0-3.0)

Ongoing Warfarin Management

• Initial INR monitoring: Check twice or three times weekly during the first 2 weeks 1
• Subsequent monitoring: Once weekly after initial stabilization, then every 4 weeks once stable 1
• Duration: Continue warfarin for the duration appropriate to the indication—minimum 3 months for VTE, indefinite for atrial fibrillation or recurrent VTE 1, 2

Special Considerations for High-Risk Patients

Very High Thrombotic Risk

For patients with recent VTE, mechanical heart valve, or severe hypercoagulable state 1, 2:

• Ensure absolutely no gap in anticoagulation coverage
• Start the parenteral agent at the exact time the next apixaban dose would have been due
• Consider more intensive INR monitoring

Concomitant Medications

• Assess for antiplatelet agents or NSAIDs that increase bleeding risk 2
• Consider whether these can be safely discontinued during transition 4

Critical Pitfalls to Avoid

Do Not Start Warfarin Alone

• Never discontinue apixaban and start warfarin without bridging 1, 3
• Warfarin takes 5-7 days to achieve therapeutic anticoagulation, creating a dangerous gap in coverage 4
• Warfarin initially causes a transient hypercoagulable state by depleting protein C before depleting clotting factors 4

Do Not Rely on Early INR Values

• INR measurements during the first few days are unreliable for warfarin dosing because apixaban affects these values 3
• Use the 5-day minimum overlap period regardless of INR values in the first 2-3 days 2

Do Not Stop Parenteral Anticoagulation Prematurely

• Both criteria must be met: ≥5 days overlap AND INR ≥2.0 for ≥24 hours 2
• Stopping based on INR alone (without completing 5 days) risks thrombosis 2

Contraindications to Consider

Before transitioning, verify the patient does not have 4, 5:

• Mechanical heart valves—warfarin is required; apixaban is contraindicated and ineffective for valve thrombosis prevention
• Moderate-to-severe mitral stenosis—warfarin is required
• End-stage CKD on dialysis—both agents have limited evidence; warfarin is preferred if anticoagulation is necessary 4