What is the recommended dosing regimen when switching from therapeutic enoxaparin (low molecular weight heparin) to apixaban (direct oral anticoagulant)?

Switching from Therapeutic Enoxaparin to Apixaban

When switching from therapeutic enoxaparin to apixaban, administer the first dose of apixaban 10 mg twice daily at the time the next scheduled dose of enoxaparin would have been due. 1

Dosing Protocol for Apixaban After Enoxaparin

Initial Treatment Phase

• First 7 days: Apixaban 10 mg orally twice daily 1, 2
• After 7 days: Continue with apixaban 5 mg orally twice daily for at least 3 months 1, 2

Timing of Switch

• Administer the first dose of apixaban when the next scheduled dose of enoxaparin would have been due
• Do not administer enoxaparin and apixaban simultaneously
• No overlap period is required between enoxaparin and apixaban 2

Special Considerations for Dose Adjustment

• Reduced dosing (2.5 mg twice daily) is required for patients with at least two of the following:

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

• Extended treatment beyond initial therapy:

  • After 6 months of initial therapy, the dose may be reduced to 2.5 mg twice daily for secondary prevention 1, 2

Clinical Evidence Supporting This Approach

Apixaban has demonstrated non-inferiority to conventional therapy (enoxaparin/warfarin) for the treatment of venous thromboembolism (VTE) with significantly lower rates of major bleeding 3. In the AMPLIFY trial, apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) was compared to conventional therapy (enoxaparin followed by warfarin) and showed:

• Similar efficacy in preventing recurrent VTE (2.3% vs 2.7%)
• Significantly lower major bleeding rates (0.6% vs 1.8%) 3

For cancer-associated thrombosis, the Caravaggio trial showed that apixaban was non-inferior to dalteparin (a low molecular weight heparin similar to enoxaparin) without increased bleeding risk 4.

Contraindications and Precautions

• Renal function: No dose adjustment needed for mild to moderate renal impairment, but avoid in severe renal impairment (CrCl <15 mL/min) 2
• Hepatic function: Contraindicated in severe hepatic impairment or hepatic coagulopathy 2
• Drug interactions: Avoid strong inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, ritonavir) 2
• Increased bleeding risk with concomitant use of:
  • Antiplatelet agents
  • NSAIDs
  • SSRIs or SNRIs 2, 5

Monitoring Recommendations

• Regular assessment of renal and hepatic function
• Monitor for signs of bleeding:
  • Unexplained bruising
  • Prolonged bleeding after minor cuts
  • Blood in urine or stool
  • Unusual headaches or dizziness 2

Common Pitfalls to Avoid

1. Overlapping anticoagulation: Unlike transitioning to warfarin, no overlap period is needed when switching from enoxaparin to apixaban
2. Missing the initial higher dosing: Failing to use the loading dose of 10 mg twice daily for the first 7 days
3. Inappropriate dose reduction: Only reduce the dose in patients meeting specific criteria
4. Inadequate patient education: Patients need clear instructions about the importance of adherence and signs of bleeding
5. Failure to consider drug interactions: Certain medications can significantly affect apixaban levels

By following this protocol for switching from therapeutic enoxaparin to apixaban, you can ensure effective anticoagulation while minimizing bleeding risk for your patients.