Apixaban Dosing for Non-Valvular Atrial Fibrillation
The standard recommended dose of apixaban (Eliquis) for patients with non-valvular atrial fibrillation is 5 mg twice daily, with dose reduction to 2.5 mg twice daily for patients who have at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2
Standard Dosing Guidelines
The dosing of apixaban for non-valvular atrial fibrillation is based on high-quality evidence from clinical trials and is reflected in both FDA labeling and clinical practice guidelines:
- Standard dose: 5 mg twice daily for most patients
- Reduced dose: 2.5 mg twice daily for patients with at least two of:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Renal Function Considerations
Unlike some other direct oral anticoagulants (DOACs), apixaban can be used across a wide range of renal function:
- Apixaban can be used in patients with creatinine clearance (CrCl) as low as 15 mL/min 1
- It can even be used in patients on hemodialysis, making it unique among DOACs 1
- No dose adjustment is required based solely on renal function unless the patient meets the criteria for dose reduction mentioned above
Clinical Evidence Supporting Apixaban Use
Apixaban has demonstrated superior efficacy and safety compared to warfarin in the ARISTOTLE trial:
- 21% reduction in stroke or systemic embolism (HR 0.79; 95% CI, 0.66-0.95) 1
- 31% reduction in major bleeding (HR 0.69; 95% CI, 0.60-0.80) 1
- 11% reduction in all-cause mortality (HR 0.89; 95% CI, 0.80-0.99) 1
Compared to other DOACs, apixaban has shown:
- Lower rates of gastrointestinal bleeding (HR 0.89; 95% CI, 0.70-1.15) compared to warfarin, unlike dabigatran and rivaroxaban which showed increased GI bleeding 1
- Consistent benefit across various patient subgroups including those with prior stroke or TIA 1
Common Pitfalls in Apixaban Dosing
Several studies have identified inappropriate dosing of apixaban in clinical practice:
- Underdosing is more common than overdosing, with approximately 34-40% of patients receiving lower than recommended doses 3, 4
- Factors associated with inappropriate dose reduction include advanced age, low body weight, and elevated serum creatinine, even when these factors don't meet the threshold for dose reduction 4
- Inappropriate dose reduction may compromise the efficacy of stroke prevention without necessarily improving safety
Special Considerations
- Temporary interruption for surgery: Discontinue apixaban at least 48 hours prior to elective surgery with moderate/high bleeding risk, or 24 hours prior to procedures with low bleeding risk 2
- Switching from warfarin: Start apixaban when INR is below 2.0 2
- Drug interactions: Consider potential interactions with strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, ritonavir)
- Adherence: The twice-daily dosing regimen requires good adherence; missing doses can significantly impact anticoagulation efficacy 5
Conclusion
When prescribing apixaban for non-valvular atrial fibrillation, follow the standard dosing of 5 mg twice daily for most patients, with dose reduction to 2.5 mg twice daily only when patients meet at least two of the specific criteria (age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL). Resist the temptation to reduce the dose based on a single criterion or general concerns about bleeding risk, as this may compromise stroke prevention efficacy.