What is the recommended dosing of apixaban (a direct oral anticoagulant) for patients with atrial fibrillation or deep vein thrombosis/pulmonary embolism?

Apixaban Dosing for Atrial Fibrillation and DVT/PE

The standard dose of apixaban is 5 mg twice daily for atrial fibrillation and 10 mg twice daily for the first 7 days followed by 5 mg twice daily for DVT/PE treatment, with dose reduction to 2.5 mg twice daily in specific populations. 1, 2

Dosing for Atrial Fibrillation

Standard Dosing

• 5 mg orally twice daily for most patients 1, 2

Dose Reduction Criteria

Reduce to 2.5 mg twice daily if patient has at least two of the following:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L) 3, 1, 2

Special Considerations

• Patients with severe renal impairment (CrCl 15-29 mL/min) should receive 2.5 mg twice daily 1
• Apixaban is the only DOAC specifically mentioned for use in dialysis patients at a dose of 2.5 mg twice daily 1

Dosing for DVT/PE Treatment

Initial Treatment

• 10 mg orally twice daily for the first 7 days 3, 1, 2

Maintenance Treatment

• 5 mg orally twice daily after the initial 7 days 3, 1, 2

Extended Treatment (Recurrence Prevention)

• After at least 6 months of treatment for DVT/PE, reduce to 2.5 mg twice daily for long-term prevention of recurrence 2

Dosing for DVT Prophylaxis After Orthopedic Surgery

• 2.5 mg orally twice daily 3, 1
• Initial dose 12-24 hours after surgery 2
• Duration:
  • Hip replacement: 35 days 2
  • Knee replacement: 12 days 2

Clinical Evidence and Outcomes

The AUGUSTUS trial demonstrated that apixaban was associated with lower bleeding rates compared to vitamin K antagonists in patients with atrial fibrillation, with no significant difference in efficacy outcomes 3, 4. When comparing standard dose (5 mg twice daily) to appropriately reduced dose (2.5 mg twice daily), both showed similar benefits over vitamin K antagonists 4.

Research has shown that patients with only one dose-reduction criterion still benefit from the standard 5 mg twice daily dose with similar safety and efficacy compared to those with no dose-reduction criteria 5. However, inappropriate underdosing is common in clinical practice, with one study showing that 60.8% of patients receiving reduced dose apixaban did not meet criteria for dose reduction 6.

Important Considerations and Pitfalls

Perioperative Management

• Discontinue apixaban at least 48 hours before elective surgery with moderate/high bleeding risk 1, 2
• Discontinue at least 24 hours before procedures with low bleeding risk 2
• Resume after adequate hemostasis is established 1, 2

Common Pitfalls to Avoid

1. Inappropriate dose reduction: Many patients receive reduced doses without meeting criteria, potentially compromising efficacy 6
2. Missed doses: If a dose is missed, take as soon as possible on the same day and resume twice-daily schedule; do not double the dose 2
3. Abrupt discontinuation: Premature discontinuation increases thrombotic risk; consider bridging with another anticoagulant if necessary 2
4. Drug interactions: While apixaban has fewer interactions than warfarin, strong dual inhibitors of CYP3A4 and P-glycoprotein may increase bleeding risk 7

Monitoring

• No routine coagulation monitoring required 1
• Regular monitoring of renal function is essential 1

By following these evidence-based dosing recommendations, clinicians can optimize the safety and efficacy of apixaban therapy for patients with atrial fibrillation and venous thromboembolism.