When is a lower dose of Eliquis (apixaban) indicated?

When to Use Lower Dose of Eliquis (Apixaban)

The lower dose of Eliquis (apixaban) 2.5 mg twice daily is indicated for patients with atrial fibrillation who meet at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Primary Indications for Lower Dose (2.5 mg twice daily)

1. Atrial Fibrillation Patients

• Dose reduction criteria - Reduce to 2.5 mg twice daily when patient meets at least two of:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 1, 2

2. Extended VTE Prevention

• After completing at least 6 months of treatment for DVT/PE at standard doses, reduce to 2.5 mg twice daily for extended prevention of recurrent VTE 1, 2

3. Severe Renal Impairment

• For patients with severe renal impairment (creatinine clearance 15-29 mL/min) 1

4. Drug Interactions

• For patients receiving standard dose (5 mg twice daily) who are also taking combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)
• Note: For patients already on 2.5 mg twice daily, avoid coadministration with these inhibitors 2

Clinical Evidence Supporting Dose Reduction

The American Society of Hematology (ASH) 2020 guidelines note that for secondary prevention of venous thromboembolism (VTE), a lower dose of apixaban (2.5 mg twice daily) may be used after completion of the primary treatment phase 3. This recommendation was based on studies showing that the lower dose had little impact on the risk of DVT compared to standard doses, with similar major bleeding risks.

The ARISTOTLE trial demonstrated that patients meeting at least two dose-reduction criteria benefited from the lower 2.5 mg twice daily dose with appropriate safety and efficacy outcomes 1, 4. Importantly, patients with only one dose-reduction criterion should receive the standard 5 mg twice daily dose, as this has been shown to be safe and efficacious 4.

Cautions and Considerations

• Inappropriate dose reduction: Studies show that inappropriate dose reduction (using 2.5 mg twice daily when only one or no criteria are met) is common but may lead to suboptimal protection against thrombotic events 5, 6

• Drug interactions: When apixaban is used with P-gp and strong CYP3A4 inhibitors, dose should be reduced by 50% for patients on standard doses, but those already on reduced doses should avoid these combinations altogether 2

• Monitoring: Although routine coagulation monitoring is not required, regular assessment of renal function is essential, particularly in elderly patients 1

• Perioperative management: Apixaban should be discontinued 48 hours before elective surgery with significant bleeding risk 1

Specific Clinical Scenarios

1. Post-PCI or ACS with atrial fibrillation:

   • The AUGUSTUS trial showed that appropriately reduced dose apixaban was associated with lower bleeding risk compared to vitamin K antagonists in patients with AF and recent ACS or PCI 5

2. Elderly patients:

   • Japanese elderly AF patients receiving on-label reduced doses based on criteria showed no significant differences in outcomes based on which specific criteria were met 7

3. Secondary prevention of VTE:

   • After completing initial treatment (10 mg twice daily for 7 days, then 5 mg twice daily), patients continuing long-term should receive 2.5 mg twice daily 2

The evidence suggests that proper adherence to dose reduction criteria is essential for optimal outcomes. Using the lower dose when not indicated may increase thrombotic risk, while failing to reduce the dose when indicated may increase bleeding risk.