What is the appropriate dosage of Eliquis (apixaban) for deep‑vein thrombosis prophylaxis?

Apixaban Dosing for DVT Prophylaxis

For DVT prophylaxis after hip or knee replacement surgery, apixaban is dosed at 2.5 mg orally twice daily, starting 12-24 hours after surgery, continued for 35 days after hip replacement or 12 days after knee replacement. 1

Standard Prophylactic Dosing

The FDA-approved regimen for VTE prophylaxis following orthopedic surgery is straightforward 1:

• Dose: 2.5 mg orally twice daily
• Initiation: 12-24 hours post-surgery
• Duration:
  • Hip replacement: 35 days 1
  • Knee replacement: 12 days 1

This prophylactic dose differs substantially from treatment doses and should not be confused with therapeutic anticoagulation regimens 2, 1.

Clinical Evidence Supporting This Regimen

The ADVANCE-2 and ADVANCE-3 trials demonstrated that apixaban 2.5 mg twice daily was superior to enoxaparin 40 mg once daily for preventing VTE after major orthopedic surgery, with comparable or lower bleeding rates 2, 3. In ADVANCE-3 (hip arthroplasty), the rate of total VTE or all-cause mortality was 1.4% with apixaban versus 3.9% with enoxaparin 2.

Important Distinctions: Prophylaxis vs. Treatment

Do not confuse prophylactic dosing with treatment dosing 1:

• Prophylaxis (post-surgical): 2.5 mg twice daily 1
• Acute DVT/PE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily 1
• Extended prevention (after completing 6 months of treatment): 2.5 mg twice daily 1

Contraindications and Precautions

Avoid apixaban for prophylaxis in patients with 4, 1:

• Creatinine clearance <15 mL/min (renal elimination accounts for 27% of clearance) 4
• Transaminases >2× upper limit of normal 4
• Total bilirubin >1.5× upper limit of normal 4

Perioperative Timing Considerations

Critical timing points 2, 5:

• Preoperative discontinuation: Stop 3 days before surgery if CrCl >30 mL/min 2
• Postoperative initiation: Start 12-24 hours after surgery once hemostasis is established 1
• Neuraxial anesthesia: If epidural catheter used, wait at least 4 hours after catheter removal before starting apixaban 5

The French Working Group on Perioperative Hemostasis strongly recommends against performing spinal or epidural procedures when apixaban concentrations may still be present due to spinal hematoma risk 2, 4.

Common Pitfalls to Avoid

• Using treatment doses for prophylaxis: The 10 mg twice daily dose is for acute VTE treatment, not prophylaxis 1
• Starting too early: Initiating before 12 hours post-surgery increases bleeding risk, especially with neuraxial anesthesia 5, 1
• Inadequate duration: Stopping prophylaxis prematurely (particularly after hip replacement, which requires 35 days) increases thrombotic risk 1, 3
• Ignoring renal function: Apixaban accumulates in renal impairment; verify CrCl before prescribing 4, 6