What is the proper dosing and administration of Direct Oral Anticoagulants (DOACs)?

How to Give DOACs

For atrial fibrillation, use standard full doses unless specific dose reduction criteria are met: apixaban 5 mg twice daily, rivaroxaban 20 mg once daily with food, dabigatran 150 mg twice daily, or edoxaban 60 mg once daily. 1

Standard Dosing by Indication

Atrial Fibrillation (Stroke Prevention)

• Apixaban: 5 mg twice daily is the standard dose 1

  • Reduce to 2.5 mg twice daily ONLY if patient meets two out of three criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥133 mmol/L 1

• Rivaroxaban: 20 mg once daily with food 1, 2

  • Reduce to 15 mg once daily if creatinine clearance 15-49 mL/min 1

• Dabigatran: 150 mg twice daily 1

  • Reduce to 110 mg twice daily if age ≥80 years or receiving concomitant verapamil 1
  • Consider dose reduction for age 75-80, moderate renal impairment (CrCl 30-50 mL/min), or patients with gastritis/GERD 1

• Edoxaban: 60 mg once daily 1

  • Reduce to 30 mg once daily if CrCl 15-50 mL/min, body weight ≤60 kg, or concomitant use of ciclosporin, dronedarone, erythromycin, or ketoconazole 1

Venous Thromboembolism (DVT/PE) Treatment

Critical: Rivaroxaban and apixaban require higher initiation doses for acute VTE, while dabigatran and edoxaban require parenteral lead-in therapy. 1

• Rivaroxaban: 15 mg twice daily with food for first 21 days, then 20 mg once daily with food 1, 2

• Apixaban: 10 mg twice daily for first 7 days, then 5 mg twice daily 1

• Dabigatran: Requires at least 5 days of parenteral anticoagulation (unfractionated heparin, LMWH, or fondaparinux) before starting 150 mg twice daily 1

• Edoxaban: Requires at least 5 days of parenteral anticoagulation before starting 60 mg once daily 1

Extended VTE Prevention (After Initial 6 Months)

• Rivaroxaban: Can reduce to 10 mg once daily with or without food 1
• Apixaban: Can reduce to 2.5 mg twice daily 1

Coronary or Peripheral Artery Disease

• Rivaroxaban: 2.5 mg twice daily in combination with aspirin 75-100 mg once daily 1, 2

Administration Considerations

Food Requirements

Rivaroxaban 15 mg and 20 mg doses MUST be taken with food to ensure adequate absorption. 2, 3

• Rivaroxaban 10 mg and 2.5 mg can be taken with or without food 1
• Apixaban, dabigatran, and edoxaban can be taken with or without food 1

Timing Consistency

• Twice-daily regimens (apixaban, dabigatran): Maintain approximately 12-hour intervals 1
• Once-daily regimens (rivaroxaban, edoxaban): Take at same time each day 1

Perioperative Management

Discontinuation Before Surgery

For low bleeding risk procedures, interrupt DOACs the night before the procedure. 4

For higher bleeding risk procedures: 4

• Rivaroxaban, apixaban, edoxaban: Discontinue 3 days (72 hours) before procedure 4
• Dabigatran:
  • If CrCl >50 mL/min: Discontinue 4 days before procedure 4
  • If CrCl 30-50 mL/min: Discontinue 5 days before procedure 4

For twice-daily regimens: Last dose should be taken on the morning of the day before surgery 4

For once-daily morning regimens: Last dose should be on the morning of the day before surgery 4

For once-daily evening regimens: Last dose should be two days before surgery 4

Resumption After Surgery

Resume DOACs at least 6 hours after the end of the procedure if adequate hemostasis is achieved. 4, 5

• Delay resumption if ongoing bleeding or surgical contraindication exists 4
• For high bleeding risk procedures, consider delaying 24-48 hours 4

Bridging Anticoagulation

Do NOT use bridging with heparin for DOACs in most situations. 4

• Bridging increases bleeding risk without reducing thrombotic risk 4
• Reserve bridging only for very high thrombotic risk patients (e.g., within 3 months of VTE) 1

Critical Pitfalls to Avoid

Dosing Errors

• Never use atrial fibrillation doses for VTE treatment - VTE requires higher doses (e.g., rivaroxaban 20 mg daily for VTE, not 15 mg) 1
• Do not underdose based on single criteria - apixaban dose reduction requires TWO out of three criteria, not just one 1
• Do not forget food requirement - rivaroxaban 15 mg and 20 mg doses are ineffective without food 2, 3

Renal Function Monitoring

Monitor creatinine clearance at baseline and periodically during treatment, especially in elderly patients. 6

• Dabigatran has highest renal elimination (80%), followed by edoxaban (50%), rivaroxaban (35%), and apixaban (25%) 3, 6
• Adjust doses according to renal function as specified above 1

Drug Interactions

Avoid combined use of strong CYP3A4 and P-glycoprotein inhibitors or inducers. 2

• Particularly important for rivaroxaban and apixaban 3
• Dabigatran, edoxaban have fewer drug interactions 3

Neuraxial Anesthesia

Never perform spinal/epidural procedures without adequate DOAC discontinuation time. 4, 2

• Risk of spinal/epidural hematoma with permanent paralysis 2
• Requires 3-5 days discontinuation depending on agent and renal function 4

Special Populations

Pregnancy

Use DOACs with extreme caution in pregnant women due to risk of obstetric hemorrhage. 2

Mechanical Heart Valves or Moderate-to-Severe Mitral Stenosis

DOACs are contraindicated - use warfarin instead. 1

Triple Positive Antiphospholipid Syndrome

DOAC use is not recommended due to increased thrombosis risk. 2