What is the recommended dosage of apixaban (Eliquis) for patients with atrial fibrillation and what adjustments should be made for impaired renal function?

Apixaban Dosing for Atrial Fibrillation

The standard dose of apixaban for atrial fibrillation is 5 mg twice daily, with dose reduction to 2.5 mg twice daily required 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

Standard Dosing Algorithm

Full-Dose Apixaban (5 mg twice daily)

• Prescribe 5 mg twice daily for patients with 0 or 1 dose-reduction criteria 1, 2
• This applies to the vast majority of patients with atrial fibrillation 3
• Patients with only one criterion (isolated advanced age, low weight, or elevated creatinine) demonstrate consistent efficacy and safety with the 5 mg dose compared to warfarin 3

Reduced-Dose Apixaban (2.5 mg twice daily)

• Reduce to 2.5 mg twice daily ONLY when at least 2 of these 3 criteria are present: 1, 4, 2
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Renal Function Adjustments

Dosing Across Renal Function Spectrum

The 2024 ACC/AHA/ACCP/HRS guidelines provide clear dosing recommendations based on creatinine clearance (CrCl): 1

• CrCl >95 mL/min: 5 mg or 2.5 mg twice daily (based on 2-of-3 criteria above)
• CrCl 51-95 mL/min: 5 mg or 2.5 mg twice daily (based on 2-of-3 criteria above)
• CrCl 31-50 mL/min: 5 mg or 2.5 mg twice daily (based on 2-of-3 criteria above)
• CrCl 15-30 mL/min: 5 mg or 2.5 mg twice daily (based on 2-of-3 criteria above)
• CrCl <15 mL/min or on dialysis: 5 mg or 2.5 mg twice daily (based on 2-of-3 criteria above)

Critical Renal Function Considerations

Apixaban has distinct advantages in renal impairment because only 27% undergoes renal excretion, making it relatively safer than other anticoagulants in this population 4. The ARISTOTLE trial excluded patients with CrCl <25 mL/min, but subsequent data support use across the renal spectrum 1.

• For CrCl 25-30 mL/min: Post-hoc analysis demonstrates apixaban causes significantly less major bleeding than warfarin (HR 0.34,95% CI 0.14-0.80), with even greater bleeding reductions than in patients with better renal function 5
• For end-stage renal disease on hemodialysis: FDA labeling recommends 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR body weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 1, 2
• Calculate CrCl using the Cockcroft-Gault equation for accurate assessment 4
• Reassess renal function at least annually, and more frequently if clinical deterioration occurs 4

Common Dosing Errors to Avoid

Inappropriate Dose Reduction

A critical pitfall is reducing the dose when only 1 criterion is present 6. Real-world data show that approximately 60% of patients receiving reduced-dose apixaban do not meet labeling criteria for dose reduction 6. This underdosing may expose patients to increased thromboembolic risk without additional safety benefit.

• Patients with isolated advanced age, low body weight, or renal dysfunction receiving 5 mg twice daily show similar efficacy (HR 0.94 vs warfarin) and safety (HR 0.68 for major bleeding vs warfarin) as those without these characteristics 3
• Do not reduce the dose based on a single criterion—this is not supported by evidence and may compromise stroke prevention 3

Verification Before Prescribing

Before prescribing reduced-dose apixaban, explicitly verify that at least 2 of the 3 criteria are met 1, 4, 2:

1. Count the criteria: age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL
2. If 0 or 1 criterion present → 5 mg twice daily
3. If 2 or 3 criteria present → 2.5 mg twice daily

Additional Clinical Considerations

No Routine Monitoring Required

• No INR monitoring is necessary with apixaban, unlike warfarin 4
• This represents a major practical advantage in clinical management

Drug Interactions

• Avoid concomitant use of strong dual P-glycoprotein and CYP3A4 inhibitors or inducers, particularly in patients with renal impairment 1
• Proton pump inhibitors do not significantly interact with apixaban 4

Missed Doses

• If a dose is missed, take it as soon as possible on the same day and resume twice-daily dosing 2
• Never double the dose to compensate for a missed dose 2

Perioperative Management

For procedures requiring temporary interruption: 1

• Low bleeding risk procedures: Hold for 1 day (if CrCl >25 mL/min)
• High bleeding risk procedures: Hold for 2 days (if CrCl >25 mL/min)
• For CrCl <25 mL/min, consider holding for an additional 1-3 days, especially for high bleeding risk procedures 1