Apixaban Dosing After 30 Days
For patients with normal renal function and no significant drug interactions, continue apixaban at 5 mg twice daily after the initial 30 days, unless the patient meets at least 2 of the 3 dose-reduction criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL). 1
Standard Dosing Algorithm
The FDA-approved dosing for apixaban in atrial fibrillation is straightforward and does not change after 30 days for most patients 1:
- 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 patients meet at least 2 of the following 3 criteria 2, 1:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Critical Evidence Supporting Continued Standard Dosing
The ARISTOTLE trial definitively demonstrated that patients with only 1 dose-reduction criterion who received 5 mg twice daily had similar efficacy (HR 0.94,95% CI 0.66-1.32) and safety (HR 0.68 for major bleeding, 95% CI 0.53-0.87) compared to warfarin, with no significant interaction based on the presence of isolated risk factors 3. This means isolated advanced age, low body weight, or renal dysfunction alone does not warrant dose reduction 3.
Common Prescribing Errors to Avoid
The most frequent error with apixaban is inappropriate dose reduction based on a single criterion rather than requiring two, with studies showing 9.4-40.4% of prescriptions involve underdosing 2. Clinicians often reduce the dose based on:
- Perceived bleeding risk without meeting formal criteria 2
- Isolated moderate renal impairment (CrCl 30-59 mL/min) 2
- Single criterion like age >80 years alone 2
This underdosing increases stroke risk without proven bleeding benefit 2.
Renal Function Considerations
Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment 2, 4:
- Moderate CKD (CrCl 30-59 mL/min): Continue 5 mg twice daily unless 2 dose-reduction criteria are met 2
- Severe CKD (CrCl 15-29 mL/min): 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 only if age ≥80 years OR weight ≤60 kg (not both required) 2
Calculate creatinine clearance using the Cockcroft-Gault equation, as this is what FDA labeling and clinical trials used for dosing decisions 2, 1.
Monitoring Requirements
- Reassess renal function at least annually 2
- Increase monitoring frequency to every 3-6 months if CrCl <60 mL/min 2
- No routine INR monitoring is required with apixaban 2
Drug Interactions Requiring Dose Adjustment
Reduce apixaban to 2.5 mg twice daily (from 5 mg or 10 mg twice daily) when coadministered with combined P-glycoprotein and strong CYP3A4 inhibitors 2, 1:
- Ketoconazole
- Itraconazole
- Ritonavir
In patients already taking 2.5 mg twice daily, avoid these inhibitors entirely 1.
Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin), as they significantly reduce apixaban levels 2.
Special Dosing Scenarios
For VTE treatment, the dosing differs from atrial fibrillation 1:
- Days 1-7: 10 mg twice daily
- After day 7: 5 mg twice daily
- For extended prophylaxis after ≥6 months of treatment: 2.5 mg twice daily
For post-surgical thromboprophylaxis (hip/knee replacement): 2.5 mg twice daily starting 12-24 hours after surgery 1.