What are the recommended dosages for Direct Oral Anticoagulants (DOACs)?

Recommended Dosages for Direct Oral Anticoagulants (DOACs)

The standard full doses of DOACs should be used unless specific dose reduction criteria are met, as inappropriate dose reduction can lead to increased thromboembolic events. 1

Standard Dosing for Each DOAC

Apixaban

• Standard dose: 5 mg twice daily 1, 2
• Reduced dose (2.5 mg twice daily) if two or more of:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥133 mmol/L (≥1.5 mg/dL) 1, 2

Dabigatran

• Standard dose: 150 mg twice daily 1
• Reduced dose (110 mg twice daily) if:
  • Age ≥80 years
  • Concomitant verapamil 1
• Consider reduced dose on individual basis if:
  • Age 75-80 years
  • Moderate renal impairment (CrCl 30-50 mL/min)
  • Gastritis, esophagitis, or gastroesophageal reflux
  • Other increased bleeding risks 1

Edoxaban

• Standard dose: 60 mg once daily 1
• Reduced dose (30 mg once daily) if any:
  • Moderate/severe renal impairment (CrCl 15-50 mL/min)
  • Body weight ≤60 kg
  • Concomitant use of ciclosporin, dronedarone, erythromycin, or ketoconazole 1

Rivaroxaban

• Standard dose: 20 mg once daily 1, 3
• Reduced dose (15 mg once daily) if:
  • CrCl 15-49 mL/min 1

Indication-Specific Dosing

Atrial Fibrillation

• Use standard doses listed above for stroke prevention 1, 4

Venous Thromboembolism (VTE) Treatment

• Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 1, 3
• Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily 1
• Edoxaban: 60 mg once daily (after 5 days of parenteral anticoagulation) 1
• Dabigatran: 150 mg twice daily (after 5 days of parenteral anticoagulation) 1

VTE Extended Prevention (after 6 months of treatment)

• Rivaroxaban: Consider reducing to 10 mg once daily 1
• Apixaban: Consider reducing to 2.5 mg twice daily 1

Post-Orthopedic Surgery VTE Prophylaxis

• Rivaroxaban: 10 mg once daily 1
• Apixaban: 2.5 mg twice daily 1
• Dabigatran: 220 mg once daily or 150 mg once daily if CrCl 30-50 mL/min 1

Special Considerations

Renal Function

• Regular monitoring of renal function is essential as all DOACs are eliminated by the kidneys to varying degrees 5
• Severe renal impairment (CrCl <15 mL/min): DOACs generally contraindicated 4
• Hemodialysis patients: Limited data; apixaban 5 mg twice daily (or 2.5 mg twice daily if dose reduction criteria met) has been studied but with insufficient power to draw definitive conclusions 6

Drug Interactions

• All DOACs are substrates of P-glycoprotein (P-gp) and may interact with strong inducers or inhibitors 7
• Rivaroxaban and apixaban are also metabolized by CYP3A4 and susceptible to drugs altering cytochrome P450 isoenzyme activities 7
• Avoid combined P-gp and strong CYP3A4 inhibitors/inducers with DOACs 3

Perioperative Management

For procedures with low bleeding risk:

• Twice daily regimens: Last dose on morning of day before procedure
• Once daily morning regimens: Last dose on morning of day before procedure
• Once daily evening regimens: Last dose two days before procedure 1

For procedures with high bleeding risk:

• Longer interruption periods based on renal function
• No bridging with heparin typically needed 1

Common Pitfalls to Avoid

1. Inappropriate dose reduction without meeting specific criteria can lead to increased thromboembolic events 1, 4

2. Failure to adjust dose based on renal function, age, weight, or drug interactions can increase bleeding risk 1

3. Combining DOACs with antiplatelet agents increases bleeding risk substantially; avoid unless specifically indicated (e.g., recent acute coronary syndrome or stent) 4

4. Switching between DOACs without clear clinical reason is not recommended 4

5. Using DOACs in contraindicated conditions such as mechanical heart valves or moderate-to-severe mitral stenosis 4

DOACs have demonstrated at least non-inferior efficacy compared to warfarin with a 50% reduction in intracranial hemorrhage risk, making them the preferred choice for most patients requiring anticoagulation 1, 4. However, proper dosing according to the specific criteria for each agent is essential to maintain this favorable risk-benefit profile.