When to Give Lower Dose Apixaban (2.5 mg Twice Daily)
Reduce apixaban to 2.5 mg twice daily only when patients meet at least 2 of the following 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2, 3
The Three-Criteria Algorithm
The dose reduction decision is based on a specific algorithm, not on renal function alone:
- Standard dose (5 mg twice daily): Use when patients have 0 or 1 dose-reduction criteria 2
- Reduced dose (2.5 mg twice daily): Use only when patients have ≥2 of these criteria 1, 2, 3:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Critical Renal Function Considerations
Renal impairment alone does NOT trigger dose reduction unless it meets the serum creatinine threshold of ≥1.5 mg/dL AND is combined with at least one other criterion. 1, 2
Moderate Renal Impairment (CrCl 30-50 mL/min)
- Continue standard dose 5 mg twice daily unless ≥2 dose-reduction criteria are met 1
- Apixaban has only 27% renal clearance, making it safer than other DOACs in renal dysfunction 1, 4
- No dose adjustment needed based on CrCl alone if >30 mL/min 1
Severe Renal Impairment (CrCl 15-29 mL/min)
- Standard dose 5 mg twice daily remains appropriate unless ≥2 dose-reduction criteria are met 1
- Reduce to 2.5 mg twice daily if ≥2 criteria present 1
End-Stage Renal Disease on Dialysis
- Standard dose 5 mg twice daily is the FDA-approved dose for stable hemodialysis patients 4, 3
- Reduce to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg 4, 3
- Pharmacokinetic data show 2.5 mg twice daily in dialysis produces drug exposure similar to 5 mg twice daily in normal renal function 4
Common Prescribing Errors to Avoid
The most frequent error is inappropriate underdosing based on a single criterion rather than requiring two criteria. 2
- Studies show 9.4-40.4% of apixaban prescriptions involve underdosing 2
- 53% of patients on low-dose apixaban were actually under-dosed inappropriately 5
- Do NOT reduce dose based solely on perceived bleeding risk without meeting formal criteria 2
- Do NOT reduce dose based on eGFR or CrCl cutoffs alone—apixaban uses the three-criteria algorithm, unlike other DOACs 2
Evidence Supporting Standard Dosing with Single Criterion
Patients with only 1 dose-reduction criterion should receive standard dose 5 mg twice daily. 6
- The ARISTOTLE trial showed patients with 1 criterion had similar efficacy (HR 0.94 vs warfarin) and safety (HR 0.68 for major bleeding) with 5 mg twice daily compared to those with no criteria 6
- No significant interaction between number of criteria and treatment effect (P=0.36 for stroke, P=0.71 for bleeding) 6
- Appropriately dosed patients at any dose had significantly better outcomes than warfarin (composite outcome 13.1% vs 18.6%, p=0.007) 5
Monitoring Requirements
Reassess renal function at least annually, more frequently if: 1, 2
- CrCl <60 mL/min (every 3-6 months recommended)
- Evidence of declining renal function
- Clinical deterioration occurs
Use Cockcroft-Gault equation to calculate CrCl for dosing decisions, as this was used in pivotal trials. 1, 2
Special Populations
Perioperative Management
- Consider reduced dose (2.5 mg twice daily) for first 2-3 days after major surgery in patients at high thromboembolism risk, then resume standard dose 7