Indications for Reduced Dose Eliquis (Apixaban)
For 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
Atrial Fibrillation Dose Reduction Criteria
The dose reduction criteria are clearly defined and must be applied strictly:
- Age ≥80 years is one criterion for dose reduction 1, 2
- Body weight ≤60 kg is the second criterion 1, 2
- Serum creatinine ≥1.5 mg/dL is the third criterion 1, 2
At least 2 of these 3 criteria must be present simultaneously to justify dose reduction to 2.5 mg twice daily. 1, 2, 3 Meeting only one criterion does not warrant dose reduction and patients should remain on the standard 5 mg twice daily dose. 2, 4
Special Renal Considerations
- For creatinine clearance >30 mL/min, no dose adjustment is needed unless other dose-reduction criteria are met 2
- For end-stage renal disease on hemodialysis, use 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: only ONE criterion needed in dialysis patients) 2
- Calculate creatinine clearance using the Cockcroft-Gault method 2
Drug Interaction Considerations
For patients receiving apixaban 5 mg twice daily who are coadministered with combined P-gp and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonaviban), decrease the apixaban dose by 50% to 2.5 mg twice daily. 3
For patients already receiving apixaban 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors entirely. 3
Note that clarithromycin, despite being a combined P-gp and strong CYP3A4 inhibitor, does not require dose adjustment based on pharmacokinetic data. 3
Venous Thromboembolism Extended-Phase Therapy
For extended-phase therapy (secondary prevention of VTE), use apixaban 2.5 mg twice daily after completing at least 6 months of standard treatment. 1, 2
The CHEST guidelines provide a weak recommendation for reduced-dose apixaban (2.5 mg twice daily) over full-dose apixaban for extended-phase anticoagulation in patients with unprovoked VTE or VTE provoked by persistent risk factors. 1 This reduced dose is specifically for secondary prevention after the initial treatment phase is complete, not for acute VTE treatment. 1
The American Society of Hematology guidelines note that apixaban has been studied at reduced dose (5 mg to 2.5 mg twice daily) for secondary prevention, though studies were not powered for direct comparisons between standard and low doses. 1
Monitoring and Reassessment
Evaluate renal function before initiation and at least annually, or when clinically indicated. 2 Reassess body weight and renal function periodically, as changes may affect whether patients meet dose-reduction criteria. 2
Critical Pitfalls to Avoid
Underdosing is common and potentially dangerous. In the AUGUSTUS trial of patients with atrial fibrillation and acute coronary syndrome/PCI, only 43% of patients receiving reduced-dose apixaban actually met the dose-reduction criteria, meaning 57% were inappropriately underdosed. 4
Do not reduce the dose based on a single criterion alone (except in hemodialysis patients where different rules apply). 2, 4 Meeting only one of the three criteria does not justify dose reduction for atrial fibrillation patients. 1, 2
Avoid combining apixaban with other anticoagulants or dual antiplatelet therapy when possible, as bleeding risk substantially increases. 3 In the ARISTOTLE trial, concomitant aspirin increased bleeding risk from 1.8% to 3.4% per year, and aspirin plus warfarin increased it from 2.7% to 4.6% per year. 3