Apixaban Dosing: 2.5 mg vs 5 mg Twice Daily
For most patients with atrial fibrillation, prescribe apixaban 5 mg twice daily; reduce to 2.5 mg twice daily ONLY when the patient meets at least 2 of these 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Standard Dosing Algorithm
The FDA-approved dosing for atrial fibrillation is straightforward but frequently misapplied:
- Standard dose: 5 mg twice daily for patients with 0 or 1 dose-reduction criteria 2, 1
- Reduced dose: 2.5 mg twice daily ONLY when ≥2 of the following criteria are met 2, 1:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
The most common prescribing error is inappropriate dose reduction based on a single criterion rather than requiring two, with studies showing 9.4-40.4% of apixaban prescriptions involve underdosing 2
Renal Function Considerations
Moderate renal impairment alone does NOT trigger dose reduction:
- CrCl 30-59 mL/min (CKD Stage 3): Use standard 5 mg twice daily unless ≥2 dose-reduction criteria are met 2, 1
- CrCl 15-29 mL/min (CKD Stage 4): Use 2.5 mg twice daily with caution 2
- End-stage renal disease on hemodialysis: FDA recommends 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (only one criterion needed in dialysis) 2
Calculate creatinine clearance using the Cockcroft-Gault equation, NOT eGFR, as this was used in pivotal trials and FDA labeling 2, 1
Apixaban has only 27% renal clearance, making it safer in renal impairment compared to dabigatran (80% renal) or rivaroxaban (66% renal) 2
Drug Interactions Requiring Dose Adjustment
- Combined P-glycoprotein AND strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): Reduce from 5 mg to 2.5 mg twice daily 1
- In patients already taking 2.5 mg twice daily: Avoid these inhibitors entirely 1
- Strong CYP3A4 inducers (rifampin): Avoid apixaban completely 2
Clinical Context for Dose Selection
The ARISTOTLE trial demonstrated that patients receiving the reduced dose of 2.5 mg twice daily (when appropriately indicated) had similar efficacy and safety profiles compared to warfarin 2
Underdosing apixaban increases stroke risk without reducing bleeding, while overdosing increases bleeding without additional efficacy benefit 2
Monitoring Requirements
- Reassess renal function at least annually 2
- Increase monitoring frequency to every 3-6 months if CrCl <60 mL/min or clinical deterioration occurs 2
- No routine INR monitoring required with apixaban 2
Special Populations
Post-orthopedic surgery VTE prophylaxis: 2.5 mg twice daily for all patients, starting 12-24 hours post-surgery (35 days for hip replacement, 12 days for knee replacement) 1
VTE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily 1
VTE secondary prevention: 2.5 mg twice daily after completing ≥6 months of treatment 1
Critical Pitfalls to Avoid
- Do NOT reduce dose based on perceived bleeding risk alone without meeting formal criteria 2
- Do NOT reduce dose for isolated renal impairment (CrCl 30-59 mL/min) unless combined with other criteria 2
- Do NOT reduce dose for isolated advanced age (<80 years) or isolated low weight (>60 kg) 2
- Do NOT use eGFR for dosing decisions—always calculate CrCl with Cockcroft-Gault 2