Apixaban Dosing for Atrial Fibrillation
The standard dose of apixaban for atrial fibrillation is 5 mg orally twice daily, with dose reduction to 2.5 mg twice daily required only when patients meet at least TWO of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Standard Dosing Algorithm
For most patients with nonvalvular atrial fibrillation, start with 5 mg twice daily. 2, 3, 1 This dosing was established in the ARISTOTLE trial of 18,201 patients, demonstrating a 21% reduction in stroke or systemic embolism compared to warfarin (HR 0.79,95% CI 0.66-0.95) and a 31% reduction in major bleeding. 4, 2, 3
Dose Reduction Criteria
Reduce to 2.5 mg twice daily ONLY if the patient meets at least TWO of these three criteria: 2, 3, 1
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Critical point: Patients with only ONE dose-reduction criterion should receive the standard 5 mg twice daily dose. 5 In the ARISTOTLE trial, 3,966 patients with a single dose-reduction criterion received 5 mg twice daily and showed consistent efficacy (HR 0.94 for stroke) and safety (HR 0.68 for major bleeding) compared to warfarin, with no significant interaction versus patients with no dose-reduction criteria. 5
Renal Function Considerations
For patients with creatinine clearance >15 mL/min not on dialysis, apply the standard dosing algorithm above. 2, 3
For patients with end-stage renal disease on hemodialysis: 4, 2, 3
- Start with 5 mg twice daily
- Reduce to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: only TWO criteria apply here, not the creatinine criterion)
Apixaban is contraindicated in patients with CrCl <15 mL/min who are NOT on dialysis. 2, 1
Drug Interaction Dose Adjustments
When using apixaban 5 mg twice daily with potent dual P-glycoprotein and CYP3A4 inhibitors (itraconazole, ketoconazole, clarithromycin, ritonavir), reduce the dose to 2.5 mg twice daily. 3, 1
Avoid concomitant use with potent P-glycoprotein and CYP3A4 inducers (carbamazepine, phenytoin, rifampin). 3, 1
Initiation and Administration
No loading dose or bridging anticoagulation is required when starting apixaban. 2, 1 The rapid onset of action eliminates the need for parenteral anticoagulation during initiation. 4
Take doses approximately 12 hours apart. 1 If a dose is missed, take it as soon as possible on the same day and resume the twice-daily schedule—do not double the dose. 1
Common Pitfall: Inappropriate Dose Reduction
A major real-world problem is inappropriate dose reduction. 6 In one study of 569 patients, 47% received the reduced 2.5 mg dose, but 61% of those did not meet labeling criteria for dose reduction. 6 Clinicians often inappropriately reduce doses based on a single criterion (particularly age alone) rather than requiring at least two criteria. This underdosing may compromise stroke prevention efficacy without additional safety benefit.
Monitoring Requirements
No routine coagulation monitoring (INR, aPTT) is required. 2 However, assess renal function before starting and at least annually thereafter, with more frequent monitoring if CrCl 30-50 mL/min or other risk factors for renal deterioration exist. 2
Special Populations
For patients with prior stroke, the same dosing algorithm applies—apixaban's benefit is independent of prior stroke history. 2 The ARISTOTLE trial demonstrated consistent benefit regardless of CHADS₂ score, CHA₂DS₂-VASc score, or prior stroke status. 4, 2
For patients requiring antiplatelet therapy after coronary intervention, clopidogrel is the preferred P2Y12 inhibitor when combined with apixaban, ideally without aspirin after a brief periprocedural period. 2