Apixaban (Eliquis) Dosing Recommendations
Standard Dosing by Indication
For nonvalvular atrial fibrillation, the standard dose is 5 mg orally 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, 3
Atrial Fibrillation
- Most patients: 5 mg orally twice daily 1, 3
- Reduced dose (2.5 mg twice daily): Required when ≥2 of these criteria are present simultaneously 1, 2, 4, 3:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL (or creatinine clearance 15-29 mL/min)
- Critical point: Patients with only 1 dose-reduction criterion should receive the standard 5 mg twice daily dose, as the ARISTOTLE trial demonstrated consistent efficacy and safety in this population 5
Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
- Acute treatment phase: 10 mg orally twice daily for the first 7 days, then 5 mg orally twice daily 1, 3
- Extended-phase therapy (secondary prevention): 2.5 mg orally twice daily after completing at least 6 months of treatment 4, 3
Post-Orthopedic Surgery Prophylaxis
- All patients: 2.5 mg orally twice daily 4, 3
- Hip replacement: Continue for 35 days, starting 12-24 hours post-surgery 3
- Knee replacement: Continue for 12 days, starting 12-24 hours post-surgery 3
Renal Impairment Considerations
No dose adjustment is needed for patients with creatinine clearance >30 mL/min unless they meet ≥2 dose-reduction criteria. 1, 2
- Normal to moderate renal impairment (CrCl >30 mL/min): No adjustment needed 1, 2
- Severe renal impairment (CrCl 15-30 mL/min): Can use either 5 mg or 2.5 mg twice daily based on whether ≥2 dose-reduction criteria are met 4
- End-stage renal disease on hemodialysis: 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: only 1 criterion needed in this population) 2, 4
- Rationale: Apixaban has only 27% renal excretion, making it suitable for severe renal impairment compared to other DOACs 4
Common Dosing Pitfalls to Avoid
The most critical error is inappropriately reducing the dose to 2.5 mg twice daily in patients with only 1 dose-reduction criterion—these patients require the full 5 mg twice daily dose. 5
- Approximately 43% of patients receiving reduced-dose apixaban in clinical practice do not meet the appropriate criteria 6
- Patients with only 1 dose-reduction criterion who received 5 mg twice daily in ARISTOTLE showed consistent benefit compared to warfarin without increased bleeding risk 5
- Do not reduce the dose based on age alone, weight alone, or renal function alone—at least 2 criteria must be present 1, 2, 4, 3
Perioperative Management
Stop apixaban at least 48 hours before high bleeding risk procedures in patients with normal/mild renal impairment, and at least 24 hours before low bleeding risk procedures. 2, 3
- Low bleeding risk procedures: Stop 2 days before surgery (normal/mild renal impairment) or 3 days before (CrCl 30-50 mL/min) 2
- High bleeding risk procedures: Stop 3 days before surgery (normal/mild renal impairment) or 4 days before (CrCl 30-50 mL/min) 2
- Neurosurgery or high hemorrhagic risk: Consider longer interruption periods of 3-5 days 1
- Bridging anticoagulation: Not generally required during the 24-48 hour interruption period 3
- Resumption: Restart as soon as adequate hemostasis is established 3
Critical Adherence Considerations
Missing even a single dose of apixaban creates a period without thromboembolic protection due to its rapid offset of action—strict adherence is essential. 2
- If a dose is missed, take it as soon as possible on the same day and resume twice-daily dosing 3
- Do not double the dose to make up for a missed dose 3
- Premature discontinuation without alternative anticoagulation increases thrombotic risk 3
Clinical Evidence Supporting Dosing
The ARISTOTLE trial demonstrated that apixaban 5 mg twice daily compared to warfarin resulted in 1, 2:
- 21% reduction in stroke or systemic embolism
- 31% reduction in major bleeding
- 11% reduction in all-cause mortality