What are the recommended oral dosing regimens of apixaban (Eliquis) for stroke prevention in non‑valvular atrial fibrillation, treatment of acute deep‑vein thrombosis (DVT) and pulmonary embolism (PE), and postoperative venous thromboembolism (VTE) prophylaxis after hip or knee replacement, and how should the dose be adjusted for age ≥ 80 years, body weight ≤ 60 kg, impaired renal function (creatinine clearance < 50 mL/min), and strong CYP3A4/P‑glycoprotein inhibitors?

Apixaban Dosing Recommendations

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

Stroke Prevention in Non-Valvular Atrial Fibrillation

Standard Dosing Algorithm

• Start with 5 mg twice daily for patients with 0 or 1 dose-reduction criteria 1, 2
• Reduce to 2.5 mg twice daily only when ≥2 of the following are present 1, 2:
  • 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—studies show 9.4–40.4% of apixaban prescriptions involve underdosing, often driven by clinician concern about renal function when formal criteria are not met. 2

Renal Function Considerations

• Moderate renal impairment (CrCl 30–59 mL/min) alone does NOT trigger dose reduction unless combined with other criteria 2, 3
• Severe renal impairment (CrCl 15–29 mL/min): Use 2.5 mg twice daily for all patients; renal impairment alone mandates this reduction 3, 2
• End-stage renal disease/dialysis (CrCl <15 mL/min): FDA recommends 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR weight ≤60 kg (only one criterion required in dialysis) 1, 4, 2

Calculate creatinine clearance using the Cockcroft-Gault equation with actual body weight—this is what FDA labeling and clinical trials used, and eGFR is not interchangeable. 2, 3

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). 2, 3

Drug Interaction Adjustments

• Combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole): Reduce from 5 mg to 2.5 mg twice daily 1, 2
• Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin): Avoid apixaban entirely 1, 2
• In patients already taking 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors 1

Treatment of Acute DVT and Pulmonary Embolism

• Initial 7 days: 10 mg twice daily 1, 3
• After 7 days: 5 mg twice daily 1, 3
• No dose adjustment for renal impairment during acute VTE treatment 5

Reduction in Risk of Recurrent DVT/PE

• After at least 6 months of treatment: 2.5 mg twice daily 1

VTE Prophylaxis After Hip or Knee Replacement

• Dose: 2.5 mg twice daily 1, 6
• Timing: Initial dose 12–24 hours after surgery 1, 6
• Duration:
  • Hip replacement: 35 days 1, 6
  • Knee replacement: 12 days 1, 6

Monitoring Requirements

• Renal function reassessment 2, 3:
  • At least annually for all patients
  • Every 3–6 months if CrCl <60 mL/min
  • Immediately with any acute illness, infection, or heart failure exacerbation
• No routine INR monitoring required 2

Perioperative Management

• Low bleeding risk procedures: Hold for 24 hours if CrCl >25 mL/min 2
• High bleeding risk procedures: Hold for 48 hours if CrCl >25 mL/min 2
• CrCl <25 mL/min: Consider holding for an additional 1–3 days, especially for high bleeding risk 2
• No bridging anticoagulation required for atrial fibrillation patients 6
• Resume when adequate hemostasis established, typically 24–72 hours postoperatively 6, 1

Switching Between Anticoagulants

From Warfarin to Apixaban

• Stop warfarin and start apixaban when INR <2.0 1, 2

From Apixaban to Warfarin

• Discontinue apixaban and begin both parenteral anticoagulant and warfarin at the time of next apixaban dose 1
• Discontinue parenteral anticoagulant when INR reaches acceptable range 1

From/To Other Anticoagulants

• Discontinue current agent and begin new agent at the time of next scheduled dose 1

Critical Pitfalls to Avoid

• Do not reduce dose based on eGFR alone—use Cockcroft-Gault calculated CrCl 2, 3
• Do not reduce dose for isolated moderate CKD (CrCl 30–59 mL/min) without meeting ≥2 criteria 2, 3
• Do not reduce dose based on perceived bleeding risk without meeting formal criteria 2
• Do not confuse stable CKD with acute renal failure—any acute illness mandates immediate renal reassessment 3
• The "2-of-3" rule applies only when CrCl >30 mL/min; for CrCl 15–30 mL/min, severe renal impairment alone mandates 2.5 mg twice daily 2, 3

Administration for Patients Unable to Swallow

• 5 mg and 2.5 mg tablets may be crushed and suspended in water, 5% dextrose in water, or apple juice, or mixed with applesauce and administered orally 1
• Crushed tablets are stable in these liquids and applesauce for up to 4 hours 1