What is the recommended apixaban (Eliquis) dosing regimen for a newly diagnosed adult with atrial fibrillation, including dose‑reduction criteria?

Apixaban (Eliquis) Dosing for New Onset Atrial Fibrillation

For most patients with newly diagnosed atrial fibrillation, start apixaban 5 mg orally twice daily; reduce to 2.5 mg twice daily ONLY when the patient meets at least 2 of the following 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Standard Dosing Algorithm

The default dose is 5 mg twice daily for stroke prevention in nonvalvular atrial fibrillation. 1, 2 This applies to the vast majority of patients, including those with:

• Moderate renal impairment (CrCl 30-59 mL/min) unless they meet ≥2 dose-reduction criteria 1
• Isolated advanced age (70-79 years) without meeting other criteria 1, 3
• Single dose-reduction criterion only (e.g., age 82 but weight 70 kg and creatinine 1.2 mg/dL) 1, 3

The ARISTOTLE trial demonstrated that patients with only 1 dose-reduction criterion who received 5 mg twice daily had similar efficacy (HR 0.94 for stroke) and safety (HR 0.68 for major bleeding) compared to warfarin, with no significant interaction based on the presence of 1 versus 0 criteria. 3

Dose Reduction Criteria: The "2 of 3" Rule

Reduce to 2.5 mg twice daily when the patient meets ≥2 of these 3 criteria: 1, 2

1. Age ≥80 years
2. Body weight ≤60 kg
3. Serum creatinine ≥1.5 mg/dL

This is an FDA-mandated algorithm that requires counting criteria, not clinical judgment about bleeding risk. 2 The most common prescribing error is inappropriate dose reduction based on a single criterion or perceived frailty—studies show 40-61% of patients receiving reduced-dose apixaban do not meet labeling criteria. 4, 5, 6

Critical Pitfall to Avoid

Do NOT reduce the dose based on: 1, 7

• eGFR alone (use serum creatinine ≥1.5 mg/dL as the criterion, not calculated CrCl cutoffs)
• Perceived bleeding risk or "frailty" without meeting formal criteria
• A single dose-reduction criterion (e.g., age 85 alone with weight 75 kg and creatinine 1.2 mg/dL warrants 5 mg twice daily)
• Moderate CKD (CrCl 30-59 mL/min) as an isolated finding

Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment compared to dabigatran (80%) or rivaroxaban (66%). 1 This pharmacokinetic profile supports standard dosing even with moderate CKD when formal dose-reduction criteria are not met.

Renal Function Considerations

Calculate creatinine clearance using the Cockcroft-Gault equation (not eGFR), as this method was used in pivotal trials and FDA labeling. 1, 7

Dosing by Renal Function:

• CrCl >30 mL/min: 5 mg twice daily (unless ≥2 dose-reduction criteria met) 1
• CrCl 15-29 mL/min: 2.5 mg twice daily with caution 1
• CrCl <15 mL/min or hemodialysis: 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (only 1 criterion required in dialysis) 1

Reassess renal function at least annually, and every 3-6 months if CrCl <60 mL/min or clinical deterioration occurs. 1, 7

Drug Interactions Requiring Dose Adjustment

Reduce from 5 mg to 2.5 mg twice daily when using combined P-glycoprotein AND strong CYP3A4 inhibitors: 1, 2

• Ketoconazole (systemic)
• Ritonavir
• Itraconazole
• Clarithromycin

Avoid apixaban entirely with strong CYP3A4 inducers: 1, 2

• Rifampin
• Carbamazepine
• Phenytoin
• St. John's wort

Practical Initiation Steps

1. Assess the 3 dose-reduction criteria (age, weight, serum creatinine—not eGFR) 2
2. Count how many criteria are present: 2
   • 0 or 1 criterion → 5 mg twice daily
   • ≥2 criteria → 2.5 mg twice daily
3. Calculate CrCl using Cockcroft-Gault to confirm safety (avoid if CrCl <15 mL/min unless dialysis) 1
4. Screen for strong CYP3A4/P-gp inhibitors or inducers and adjust accordingly 1
5. Start immediately—no loading dose or bridging required for new-onset AF 1, 2

Special Cardioversion Considerations

If cardioversion is planned within 48 hours of AF onset, ensure at least one dose of apixaban ≥4 hours before cardioversion (or ≥2 hours after a 10 mg loading dose, though this is off-label). 1 If AF duration >48 hours, either:

• Anticoagulate for ≥3 weeks before cardioversion, or
• Perform transesophageal echocardiography to exclude thrombus before cardioversion 1

Continue anticoagulation for ≥4 weeks post-cardioversion regardless of rhythm outcome. 1

Monitoring Requirements

• No routine INR monitoring required (unlike warfarin) 1, 7
• Renal function annually (or every 3-6 months if CrCl <60 mL/min) 1, 7
• Reassess dose-reduction criteria annually as weight, renal function, and age change 7
• Monitor for bleeding symptoms, particularly gastrointestinal bleeding in elderly patients 7