Apixaban Dosing for Atrial Fibrillation
The standard recommended dose of apixaban for patients with non-valvular atrial fibrillation is 5 mg taken orally twice daily, with a reduced dose of 2.5 mg twice daily for patients with 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 Regimen
- For most patients with atrial fibrillation: 5 mg twice daily
- This dosing has been shown to reduce stroke or systemic embolism by 21% compared to warfarin (HR 0.79; 95% CI, 0.66-0.95) 2
- Apixaban also reduces all-cause mortality by 11% (HR 0.89; 95% CI, 0.80-0.998) compared to warfarin 3
Dose Reduction Criteria
Reduce to 2.5 mg twice daily if the patient has at least two of:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL 1
Renal Function Considerations
- For patients with severe renal impairment (CrCl 15-29 mL/min), the reduced dose of 2.5 mg twice daily is recommended 2
- No dose adjustment is needed for mild to moderate renal impairment alone 2
- For patients with end-stage renal disease requiring hemodialysis: 5 mg twice daily, reduce to 2.5 mg twice daily if age ≥80 years or body weight ≤60 kg 3
Important Clinical Considerations
Medication Administration
- Apixaban can be taken with or without food 2
- Can be crushed and administered via nasogastric tube if needed without altering bioavailability 2
- If a dose is missed, it should be taken as soon as possible on the same day; do not double the dose to make up for a missed dose 1
Perioperative Management
- Discontinue apixaban at least 48 hours prior to elective surgery with moderate or high bleeding risk 1
- Discontinue at least 24 hours prior to procedures with low bleeding risk 1
- Resume after surgical procedures once adequate hemostasis is established 1
Contraindications
- Mechanical heart valves
- Moderate-to-severe mitral stenosis 2
- Active pathological bleeding
Monitoring
- Regular assessment for bleeding signs
- Periodic renal function monitoring, especially in elderly patients 2
Clinical Evidence
The ARISTOTLE trial demonstrated that apixaban 5 mg twice daily (with appropriate dose reductions) was superior to warfarin for stroke prevention in atrial fibrillation, with a 31% reduction in major bleeding (HR 0.69; 95% CI, 0.60-0.80) and a 49% reduction in hemorrhagic stroke 2.
Patients with one dose-reduction criterion who received the standard 5 mg twice daily dose showed consistent benefits compared to warfarin, similar to those without any dose-reduction criteria 4. This confirms the appropriateness of the standard dosing regimen for these patients.
Common Pitfalls to Avoid
Inappropriate underdosing: Lower than recommended dosing in older adults may still result in higher than expected plasma concentrations and potentially increase bleeding risk without additional benefit 5
Failure to adjust dose: Not reducing the dose when patients meet two or more dose-reduction criteria can increase bleeding risk
Abrupt discontinuation: Never stop apixaban abruptly due to increased stroke risk; if discontinuation is necessary, consider transitioning to another anticoagulant 1
Drug interactions: Monitor for interactions with strong inhibitors of both CYP3A4 and P-glycoprotein, which may increase apixaban levels 2
By following these evidence-based dosing recommendations, clinicians can optimize stroke prevention while minimizing bleeding risk in patients with atrial fibrillation.