What are the criteria for a low dose of Eliquis (apixaban)?

Criteria for Low-Dose Eliquis (Apixaban 2.5 mg Twice Daily)

Atrial Fibrillation Dose Reduction

For patients with atrial fibrillation, reduce apixaban from 5 mg twice daily to 2.5 mg twice daily only when at least 2 of the following 3 criteria are present: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2, 3

The Three Dose-Reduction Criteria:

• Age ≥80 years - This alone is insufficient for dose reduction; must be combined with at least one other criterion 1, 2
• Body weight ≤60 kg - This alone is insufficient for dose reduction; must be combined with at least one other criterion 1, 2
• Serum creatinine ≥1.5 mg/dL - This alone is insufficient for dose reduction; must be combined with at least one other criterion 1, 2

Critical Implementation Points:

• At least 2 of these 3 criteria must be present simultaneously to justify the reduced dose 1, 2, 3
• If a patient has only 0 or 1 criterion, the standard dose of 5 mg twice daily should be used 2
• Use the Cockcroft-Gault equation (not eGFR) to calculate creatinine clearance for proper assessment 1, 4

Special Renal Function Consideration:

• Creatinine clearance 15-29 mL/min alone qualifies for dose reduction to 2.5 mg twice daily, even without meeting the other two criteria 1
• For creatinine clearance >30 mL/min, no dose adjustment is needed unless at least 2 of the 3 standard criteria are met 1

End-Stage Renal Disease on Hemodialysis:

• Use 5 mg twice daily as the standard dose 1, 2
• Reduce to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: only 1 criterion needed in this population, not 2) 1, 2

Other Indications for 2.5 mg Twice Daily

Post-Orthopedic Surgery Prophylaxis:

• All patients receive 2.5 mg twice daily for DVT prophylaxis after hip or knee replacement surgery 1, 3
• Initial dose should be taken 12-24 hours after surgery 3
• Duration: 35 days for hip replacement, 12 days for knee replacement 3

Extended-Phase VTE Treatment (Secondary Prevention):

• After completing at least 6 months of standard anticoagulation for DVT/PE, reduce to 2.5 mg twice daily for long-term secondary prevention 1, 3
• This applies to unprovoked VTE or VTE with persistent risk factors 1

Common Pitfalls to Avoid

Dosing Errors:

• Do not reduce the dose based on a single criterion - this is the most common prescribing error 1, 2
• Approximately 43-57% of patients receiving reduced-dose apixaban in clinical practice do not meet the appropriate criteria 5, 6
• Off-label underdosing (using 2.5 mg twice daily without meeting criteria) occurs in approximately 15-17% of older adults with atrial fibrillation 6

Assessment Errors:

• Do not use eGFR for dose adjustment decisions; always use Cockcroft-Gault calculated creatinine clearance 1, 4
• Patient weight is frequently not documented in electronic health records, leading to inappropriate dosing decisions 7
• Serum creatinine ≥1.5 mg/dL is the criterion, not creatinine clearance thresholds (except for the 15-29 mL/min exception noted above) 1, 2

Monitoring Requirements:

• Reassess renal function at least annually, and more frequently if clinical deterioration occurs 1, 2
• Reevaluate body weight and renal function periodically, as changes may affect whether dose-reduction criteria are met 1
• No routine INR monitoring is required with apixaban 2

Clinical Outcomes Data

Efficacy and Safety of Reduced Dosing:

• The ARISTOTLE trial demonstrated that patients receiving appropriately reduced-dose apixaban (2.5 mg twice daily) had similar efficacy and safety profiles compared to warfarin 2, 8
• Apixaban concentrations are lower with 2.5 mg twice daily compared to 5 mg twice daily, but reductions in coagulation biomarkers (D-dimer, prothrombin fragment 1+2) remain consistent 8
• The clinical effects on stroke prevention, major bleeding reduction, and mortality are consistent between appropriately reduced-dose and standard-dose apixaban when compared to warfarin 5, 8

Off-Label Underdosing Concerns:

• Off-label reduced dosing (without meeting criteria) has not shown significant differences in stroke or bleeding outcomes in observational studies, though all-cause mortality was higher in the underdosed group 6
• Older adults receiving apixaban in clinical practice often have higher drug concentrations than expected from clinical trial data, raising questions about optimal dosing in real-world populations 9