Apixaban Dosing for Atrial Fibrillation
Standard Dose: 5 mg Twice Daily
The standard dose of apixaban for stroke prevention in non-valvular atrial fibrillation is 5 mg orally twice daily for most patients. 1
This dosing regimen was established in the ARISTOTLE trial, which demonstrated apixaban's superiority over warfarin with a 21% reduction in stroke or systemic embolism (HR 0.79,95% CI 0.66-0.95) and a 31% reduction in major bleeding. 2, 3
The 5 mg twice-daily dose applies to all patients with normal renal function (CrCl >30 mL/min) who do not meet the specific dose-reduction criteria outlined below. 2, 3
Dose Reduction Criteria: The "2-of-3 Rule"
Reduce apixaban to 2.5 mg twice daily ONLY when a patient meets at least TWO of the following THREE criteria: 1, 2
Meeting only ONE criterion does NOT justify dose reduction—this is the most common prescribing error with apixaban, occurring in 9.4-40.4% of prescriptions. 4, 5
The reduced dose was specifically validated in the ARISTOTLE trial for patients meeting ≥2 criteria and showed similar efficacy and safety to warfarin in this subgroup. 2, 4
Renal Function Considerations
Calculate creatinine clearance using the Cockcroft-Gault equation (not eGFR), as this method was used in pivotal trials and FDA labeling. 3, 4
Dosing by Renal Function:
| CrCl (mL/min) | Recommended Dose | Key Points |
|---|---|---|
| >30 | 5 mg twice daily (unless ≥2 dose-reduction criteria met) | Standard dosing applies [3,4] |
| 15-29 | 2.5 mg twice daily (mandatory for all patients) | Severe renal impairment alone mandates dose reduction [4,1] |
| <15 or dialysis | 5 mg twice daily; reduce to 2.5 mg if age ≥80 OR weight ≤60 kg (only ONE criterion needed) | FDA-approved but controversial; warfarin preferred [6,4] |
Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment compared to dabigatran (80% renal) or rivaroxaban (66% renal). 3, 4
Reassess renal function at least annually, or every 3-6 months if CrCl <60 mL/min. 6, 4
Drug Interactions Requiring Dose Adjustment
Reduce apixaban from 5 mg to 2.5 mg twice daily when using combined P-glycoprotein AND strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, itraconazole). 6, 4, 1
Avoid apixaban entirely with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) as they significantly reduce apixaban levels. 6, 4, 1
Common Prescribing Pitfalls to Avoid
Do NOT reduce the dose based on a single criterion (e.g., age 78 years alone, weight 62 kg alone, or moderate CKD with CrCl 45 mL/min alone). 3, 4, 5
Do NOT reduce the dose based on perceived bleeding risk, frailty, or fall risk without meeting the formal 2-of-3 criteria. 3, 4
Do NOT use eGFR for dosing decisions—always calculate CrCl with Cockcroft-Gault using actual body weight. 3, 4
Do NOT underdose patients with moderate CKD (CrCl 30-59 mL/min) unless they meet ≥2 dose-reduction criteria; this is a frequent error driven by clinician concern about renal function. 3, 4
Special Clinical Scenarios
Hepatic Impairment
- Apixaban is not recommended in severe hepatic impairment (transaminases >2× upper limit of normal or total bilirubin >1.5× upper limit of normal). 6, 1
Perioperative Management
- Hold apixaban for 1 day before low-bleeding-risk procedures and 2 days before high-bleeding-risk procedures if CrCl >25 mL/min. 6
- No bridging anticoagulation is required; resume 24-48 hours post-procedure once hemostasis is confirmed. 6
Switching from Warfarin
- Stop warfarin and start apixaban when INR falls below 2.0; no bridging therapy is needed. 6
Atrial Flutter
- All dosing recommendations for atrial fibrillation apply directly to atrial flutter. 4