What is the recommended initial dosing of apixaban (Eliquis) for a patient, and how should it be adjusted for severe renal impairment, age ≥ 80 years, or weight ≤ 60 kg?

Apixaban (Eliquis) Initial Dosing

For atrial fibrillation, start apixaban 5 mg twice daily in most patients; reduce to 2.5 mg twice daily only when the patient meets at least TWO of these three criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Standard Dosing by Indication

Atrial Fibrillation (Stroke Prevention)

• 5 mg twice daily is the standard dose for most patients with nonvalvular atrial fibrillation 1, 3
• 2.5 mg twice daily only when meeting ≥2 of the following three criteria 1, 3, 2:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Critical pitfall: The single most common prescribing error is reducing the dose based on only ONE criterion (e.g., age 78 years alone, or moderate CKD alone)—this leads to underdosing in 9.4–40.4% of prescriptions and inferior outcomes 2

Venous Thromboembolism (DVT/PE Treatment)

• 10 mg twice daily for the first 7 days, then 5 mg twice daily thereafter 3, 1
• No renal dose adjustment for VTE treatment—the "2-of-3" rule does NOT apply to acute VTE 2

Post-Orthopedic Surgery Prophylaxis

• 2.5 mg twice daily starting 12–24 hours after surgery 1
• Duration: 35 days for hip replacement, 12 days for knee replacement 1

Extended VTE Prevention (After 6 Months)

• 2.5 mg twice daily for secondary prevention after completing initial VTE treatment 1

Renal Function Adjustments

Creatinine Clearance >30 mL/min

• Use standard 5 mg twice daily for atrial fibrillation unless ≥2 dose-reduction criteria are met 2, 4
• Moderate CKD (CrCl 30–59 mL/min) alone does NOT trigger dose reduction 2

Creatinine Clearance 15–29 mL/min (Severe Renal Impairment)

• 2.5 mg twice daily for ALL patients regardless of age or weight 2, 4
• This is mandatory dose reduction based on renal function alone 2

Creatinine Clearance <15 mL/min or Dialysis

• FDA-approved: 5 mg twice daily; reduce to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (only ONE criterion required in dialysis) 2, 5, 1
• European guidelines contraindicate apixaban in dialysis patients, highlighting regulatory divergence 5
• Observational data from 25,523 dialysis patients showed standard-dose apixaban (5 mg twice daily) superior to both reduced-dose and warfarin for stroke prevention and mortality 5

Calculate creatinine clearance using the Cockcroft-Gault equation—do NOT use eGFR, as trials and FDA labeling relied on Cockcroft-Gault 2, 4

Drug Interaction Adjustments

• Reduce to 2.5 mg twice daily when using combined P-glycoprotein AND strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole) 2, 4
• Avoid apixaban entirely with strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) 2, 4

Pharmacokinetic Rationale

• Apixaban has only 27% renal clearance, making it the safest DOAC in renal impairment compared to dabigatran (80%) or rivaroxaban (66%) 3, 2, 4
• This low renal dependence provides a wider safety margin as kidney function declines 2

Monitoring Requirements

• Reassess renal function at least annually; increase to every 3–6 months if CrCl <60 mL/min 2, 4
• No routine INR monitoring required 2
• Monitor for bleeding symptoms, particularly gastrointestinal in elderly patients 2

Common Pitfalls to Avoid

• Do NOT reduce dose based on perceived bleeding risk, frailty, or isolated moderate CKD without meeting formal criteria 2
• Do NOT use eGFR for dosing—always calculate CrCl with Cockcroft-Gault using actual body weight 2, 4
• Do NOT underdose in dialysis patients—standard 5 mg twice daily shows superior outcomes unless age/weight criteria met 5
• Do NOT bridge with heparin when starting apixaban—simply begin oral therapy 2