What is the recommended dose of Novel Oral Anticoagulants (NOACs) for the treatment of pulmonary embolism?

Recommended Doses of NOACs for Pulmonary Embolism Treatment

For the treatment of pulmonary embolism, the recommended NOAC dosing regimens are: dabigatran 150 mg twice daily after 5-10 days of parenteral anticoagulation; rivaroxaban 15 mg twice daily for 3 weeks followed by 20 mg once daily; apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily; and edoxaban 60 mg once daily (reduced to 30 mg daily for CrCl 30-50 mL/min or weight <60 kg) after at least 5 days of parenteral anticoagulation. 1

Specific NOAC Dosing Regimens

Dabigatran

• Dose: 150 mg twice daily 1, 2
• Initial therapy: Must be preceded by 5-10 days of parenteral anticoagulation 2
• Renal considerations:
  • For CrCl >30 mL/min: 150 mg twice daily
  • For CrCl ≤30 mL/min or on dialysis: Dosing recommendations cannot be provided 2
  • For CrCl <50 mL/min with concomitant P-gp inhibitors: Avoid coadministration 2

Rivaroxaban

• Initial dose: 15 mg twice daily for 3 weeks 1
• Maintenance dose: 20 mg once daily 1
• Advantage: Single oral drug approach without need for initial parenteral anticoagulation 3
• Clinical evidence: Non-inferior to standard therapy with potentially improved benefit-risk profile 4
• Hospital stay: Associated with shorter hospitalization compared to standard therapy (6 days vs 8 days) 5

Apixaban

• Initial dose: 10 mg twice daily for 7 days 1
• Maintenance dose: 5 mg twice daily 1
• Advantage: Single oral drug approach without need for initial parenteral anticoagulation 3
• Safety profile: Lower rates of major bleeding compared to conventional therapy 1
• Cancer-associated VTE: Non-inferior to dalteparin without increased bleeding risk 6

Edoxaban

• Dose: 60 mg once daily 1
• Dose adjustment: 30 mg once daily for CrCl 30-50 mL/min or body weight <60 kg 1
• Initial therapy: Must be preceded by at least 5 days of parenteral anticoagulation 1
• Efficacy: Non-inferior to warfarin with lower rates of clinically relevant bleeding 1

Important Clinical Considerations

Renal Function Assessment

• Assess renal function prior to initiating any NOAC 2
• Monitor renal function periodically, especially in situations that may lead to decline in function 2
• Adjust therapy or consider alternative anticoagulation based on renal function changes 2

Contraindications and Cautions

• All NOACs are contraindicated in severe renal failure (CrCl <30 mL/min) 3
• Anti-Xa inhibitors (rivaroxaban, apixaban, edoxaban) are contraindicated in liver insufficiency 3
• Avoid concomitant use of P-gp inhibitors in patients with reduced renal function 2

Monitoring

• Routine laboratory monitoring is not required for NOACs 3
• When necessary, use aPTT or ECT (not INR) to assess anticoagulant activity for dabigatran 2

Potential Pitfalls and Caveats

• Dosing errors can occur due to different dosing schedules between NOACs - verify correct medication and dose 7
• The evidence for NOACs in PE comes from trials with relatively young patients with few comorbidities 1
• Cancer patients may require special consideration - apixaban has shown non-inferiority to LMWH 6
• Ensure proper transition from parenteral anticoagulation to oral therapy when using dabigatran or edoxaban 1
• Be vigilant about renal function changes which may necessitate dose adjustments or medication changes 2

NOACs offer a simplified treatment approach compared to conventional therapy while maintaining efficacy and potentially improving safety profiles. The choice between agents should consider the specific dosing regimen, need for initial parenteral therapy, renal function, and potential drug interactions.