1.1. Adults

Direct oral anticoagulants (DOACs) are FDA-approved to treat and prevent deep venous thrombosis (DVT) and pulmonary embolism (PE), reduce the risk of stroke and systemic embolism from non-valvular atrial fibrillation, and to be used as prophylaxis against DVT and PE after knee and hip surgery. DOACs work by interfering with pathways in the coagulation cascade: directly inhibiting thrombin (e.g., dabigatran); or selectively, reversibly inhibiting factor Xa (e.g., apixaban, edoxaban, rivaroxaban)1-7. In April 2020, Portola Pharmaceuticals removed Bevyxxa® (betrixaban) from the market for independent business reasons8 .

Maximum recommended adult dosages for DOACs are summarized in Tables 1 and 2. Medication profiles identifying patients prescribed dosages exceeding these recommendations will be reviewed.

Table 1. Maximum Daily Adult Dosages for DOACs: Direct Thrombin Inhibitors1-4
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
dabigatran (Pradaxa®) 75 mg, 110 mg, 150 mg capsules Reduction in risk of stroke and systemic embolism in non-valvular AF
  • CrCl greater than 30 mL/min:
    • 50 mg twice daily
  • CrCl 15-30 mL/min:
    • 75 mg twice daily
  • CrCl less than 15 mL/ min:
    • dosing recommendations cannot be provided
  • CrCl 30-50 mL/min with concomitant use of P-gp inhibitors:
    • 75 mg twice daily
  • CrCl less than 30 mL/min with concomitant use of P-gp inhibitors:
    • Avoid coadministration
dabigatran   Treatment of DVT and PE/reduction in the risk of recurrence of DVT and PE
  • CrCl greater than 30 mL/ min:
    • 150 mg twice daily*
  • CrCl less than or equal to 30 mL/ min:
    • dosing recommendations cannot be provided
  • CrCl less than 50 mL/ min with concomitant use of P-gp inhibitors:
    • Avoid coadministration
dabigatran   Prophylaxis of DVT and PE following hip replacement surgery
  • CrCl greater than 30 mL/min:
    • 110 mg for first day, then 220 mg once daily
  • CrCl less than or equal to 30 mL/ min:
    • dosing recommendations cannot be provided
  • CrCl less than 50 mL/ min with concomitant use of P-gp inhibitors:
    • Avoid coadministration
       

Legend:

  • AF = atrial fibrillation
  • DVT = deep venous thrombosis
  • PE = pulmonary embolism
  • *Requires 5 to 10 days parenteral therapy before initiation of therapy
Table 2. Maximum Daily Adult Dosages for DOACs: Factor Xa Inhibitors1,2,5-7
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
apixaban (Eliquis®) 2.5 mg, 5 mg tablets Reduction of risk of stroke and systemic embolism in patients with non-valvular AF 5 mg twice daily#
apixaban   Prophylaxis of DVT following hip or knee replacement surgery 2.5 mg twice daily
apixaban   Treatment of DVT and PE 10 mg twice daily for 7 days, then 5 mg twice daily
apixaban   Reduction in risk of recurrence of DVT and PE 2.5 mg twice daily^
edoxaban (Savaysa®) 15 mg, 30 mg, 60 mg tablets

Non-valvular AF: 

CrCl greater than 50 mL/min and less than or equal to 95 mL/min

 60 mg once daily+
edoxaban  

Non-valvular AF:

CrCl 15-50 mL/min

 30 mg once daily
edoxaban  

Treatment of DVT and PE:

greater than or equal to 60 kg

 60 mg once daily*
edoxaban  

Treatment of DVT and PE:

less than 60 kg, CrCl 15-50 mL/min, adjunctive therapy with certain P-gp inhibitors

 30 mg once daily*
rivaroxaban (Xarelto®) 2.5 mg, 10 mg, 15 mg, 20 mg tablets, 1 mg/ 1 mL granules for suspension Reduction in the risk of stroke in non-valvular AF, CrCl greater than 50 mL/min 20 mg once daily with evening meal
rivaroxaban   Reduction in the risk of stroke in non-valvular AF, CrCl less than or equal to 50 mL/min 15 mg once daily with evening meal
rivaroxaban   Treatment of DVT and PE, CrCl greater than or equal to 15 mL/min 15 mg twice daily for 21 days, then 20 mg once daily
rivaroxaban   Reduction in risk of recurrence of DVT and PE (following initial treatment), CrCl greater than or equal to 15 mL/min 10 mg once daily^
rivaroxaban   Prophylaxis of DVT following hip or knee replacement surgery, CrCl greater than or equal to 15 mL/min 10 mg once daily
rivaroxaban   VTE prophylaxis in hospitalized adults with acute illness and limited mobility and other risk factors for VTE, CrCl greater than or equal to 15 mL/min 10 mg once daily
rivaroxaban   Reduction of major cardiovascular event risk in patients with chronic coronary heart disease, peripheral artery disease 2.5 mg twice daily, plus aspirin 75-100 mg once daily

Legend

  • AF = atrial fibrillation
  • DVT = deep venous thrombosis
  • PE = pulmonary embolism
  • P-gp = P-glycoprotein
  • VTE = venous thromboembolism
  • + Avoid in patients with CrCl greater than 95 ml/min due to increased risk of ischemic stroke compared to warfarin
  • * Requires 5 to 10 days parenteral therapy before initiation of therapy
  • # Dose should be decreased to 2.5 mg twice daily in patients receiving strong inhibitors of both CYP3A4 and P-glycoprotein concurrently, or those with at least two of the following: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL
  • ^ Following at least 6 months of DVT or PE treatment

1.2. Pediatrics

Apixaban and edoxaban are not recommended for use in pediatric patients, as the safety and efficacy have not been established for these agents in this patient population .1,2,5,6 .

In June 2021, the FDA approved Pradaxa® (dabigatran) oral pellets to treat venous thromboembolism after receiving at least five days of injectable or intravenous treatment for blood clots and to reduce the risk of recurrent thromboembolism in patients 3 months to less than twelve years of age who have completed treatment for a previous venous thromboembolism9.

Dabigatran oral capsules were approved to treat venous thromboembolism after receiving at least five days of injectable or intravenous treatment for blood clots and to reduce the risk of recurrent thromboembolism in patients 8 years of age and older who have completed treatment for a previous venous thromboembolism9.

In December 2021, the FDA approved Xarelto® (rivaroxaban) tablets and oral suspension to treat venous thromboembolism and to reduce the risk of recurrent venous thromboembolism in patients less than 18 years of age who received at least five days of injectable or intravenous treatment for blood clots. Rivaroxaban was also approved to reduce the risk of blood clots in patients two years of age and older with congenital heart disease after the Fontan procedure10 .

Maximum recommended pediatric dosages for DOACs are summarized in Table 3 through Table 6. Medication profiles identifying patients prescribed dosages exceeding these recommendations will be reviewed.

Table 3. Maximum Daily Pediatric Dosages for DOACs in Pediatric Patients Less than 2 Years of Age: Direct Thrombin Inhibitors1,2,4
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
dabigatran (Pradaxa®) oral pellets! 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, 150 mg oral pellets Treatment of VTE and to reduce the risk of VTE recurrence: 3 months to less than or equal to 2 years of age
  • Actual Weight: 3kg to less than 4kg*^
    • 3 to less than 6 months: 30 mg twice daily
  • Actual Weight: 4 kg to less than 5 kg*^
    • 3 to less than 10 months: 40 mg twice daily
  • Actual Weight: 5 kg to less than 7 kg*^
    • 3 to less than 5 months: 40 mg twice daily
    • 5 to less than 24 months: 50 mg twice daily
  • Actual Weight: 7 kg to less than 9 kg*^
    • 3 to less than4 months: 50 mg twice daily
    • 4 to less than 9 months: 60 mg twice daily
    • 9 to less than24 months: 70 mg twice daily
  • Actual Weight: 9 kg to less than 11 kg*^
    • 5 to less than 6 months: 60 mg twice daily
    • 6 to less than 11 months: 80 mg twice daily
    • 11 to less than 24 months: 90 mg twice daily
  • Actual Weight: 11 kg to less than 13 kg*^
    • 8 to less than 18 months: 100 mg twice daily
    • 18 to less than 24 months: 110 mg twice daily
  • Actual Weight: 13 kg to less than 16 kg*^
    • 10 to less than 11 months: 100 mg twice daily
    • 11 to less than 24 months: 140 mg twice daily
  • Actual Weight: 16 kg to less than 21 kg*^
    • 12 to less than 24 months: 140 mg twice daily
  • Actual Weight: 21 kg to less than 26 kg*^
    • 18 to less than 24 months: 180 mg twice daily

Legend

  • VTE = venous thromboembolism
  • ! Avoid dabigatran in patients with a CrCl less than 50 mL/min
  • * Requires at least 5 days of parenteral therapy before initiation of therapy for the treatment of VTE
  • ^ Following appropriate treatment duration of DVT or PE treatment if used to reduce the risk of VTE recurrence
Table 4. Maximum Daily Pediatric Dosages for DOACs in Pediatric Patients 2 to Less than 12 Years of Age: Direct Thrombin Inhibitors1,2,4
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
dabigatran (Pradaxa®) oral pellets! 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, 150 mg oral pellets Treatment of VTE and to reduce the risk of VTE recurrence: 2 to less than 12 years of age
  • Actual Weight: 7 kg to less than 9 kg*^
    • 70 mg twice daily
  • Actual Weight: 9 kg to less than 11 kg*^
    • 90 mg twice daily
  • Actual Weight: 11 kg to less than 13 kg*^
    • 110 mg twice daily
  • Actual Weight: 13 kg to less than 16 kg*^ 
    • 140 mg twice daily
  • Actual Weight: 16 kg to less than 21 kg*^
    • 170 mg twice daily
  • Actual Weight: 21 kg to less than 41 kg*^
    • 220 mg twice daily
  • Actual Weight: 41 kg or greater*^
    • 260 mg twice daily
       

Legend

  • VTE = venous thromboembolism
  • ! Avoid dabigatran in patients with a CrCl less than 50 mL/min
  • * Requires at least 5 days of parenteral therapy before initiation of therapy for the treatment of VTE
  • ^ Following appropriate treatment duration of DVT or PE treatment if used to reduce the risk of VTE recurrence
Table 5. Maximum Daily Pediatric Dosages for DOACs in Pediatric Patients 8 to Less than 18 Years of Age: Direct Thrombin Inhibitors1-3
Drug Name

 

Dosage Form/Strength

 Treatment Indication Maximum Recommended Dosage
dabigatran (Pradaxa®) capsules! 75 mg, 110 mg, 150 mg oral capsules Treatment of VTE and to reduce the risk of VTE recurrence: 8 to less than 18 years of age 11 kg to less than 16 kg*^
75 mg twice daily
16 kg to less than 26 kg*^
110 mg twice daily
26 kg to less than 41 kg*^
150 mg twice daily
41 kg to less than 61 kg*^ 
185 mg twice daily
61 kg to less than 81 kg*^
220 mg twice daily
81 kg or greater*^
260 mg twice daily

Legend

  • VTE = venous thromboembolism
  • ! Avoid dabigatran in patients with a CrCl less than 50 mL/min
  • * Requires at least 5 days of parenteral therapy before initiation of therapy for the treatment of VTE
  • ^ Following appropriate treatment duration of DVT or PE treatment if used to reduce the risk of VTE recurrence
Table 6. Maximum Daily Pediatric Dosages for DOACs in Patients Less than 18 Years of Age: Factor Xa Inhibitors1,2,7
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage±
rivaroxaban (Xarelto®) 10 mg, 15 mg, 20 mg tablets, 1 mg/ 1 mL granules for suspension Treatment of VTE and to reduce the risk of VTE recurrence: less than 18 years of age
  • 2.6 kg to 2.9 kg*^#
    • 0.8 mg three times daily
  • 3 kg to 3.9 kg*^#
    • 0.9 mg three times daily
  • 4 kg to 4.9 kg*^#
    • 1.4 mg three times daily
  • 5 kg to 6.9 kg*^#
    • 1.6 mg three times daily
  • 7 kg to 7.9 kg*^#
    • 1.8 mg three times daily
  • 8 kg to 8.9 kg*^#
    • 2.4 mg three times daily
  • 9 kg to 9.9 kg*^#
    • 2.8 mg three times daily
  • 10 kg to 11.9 kg*^#
    • 3 mg three times daily
  • 12 kg to 29.9 kg*^#
    • 5 mg twice daily
  • 30 kg to 49.9 kg*^!
    • 15 mg once daily
  • greater than or equal to 50 kg*^!
    • 20 mg once daily
    Thromboprophylaxis in patients 2 years of age and older with congenital heart disease who have undergone Fontan procedure
  • 7 kg to 7.9 kg#
    • 1.1 mg twice daily
  • 8 kg to 9.9 kg#
    • 1.6 mg twice daily
  • 10 kg to 11.9 kg#
    • 1.7 mg twice daily
  • 12 kg to 19.9 kg#
    • 2 mg twice daily
  • 20 kg to 29.9 kg#
    • 2.5 mg twice daily
  • 30 kg to 49.9 kg#
    • 7.5 mg once daily
  • greater than or equal to 50 kg!
    • 10 mg once daily

Legend

  • VTE = venous thromboembolism
  • ± Patients less than 6 months of age should meet the following criteria: at birth at least 37 weeks gestation, have at least 10 days of oral feeding, and weigh greater than or equal to2.6 kg at the time of dosing
  • * Requires at least 5 days parenteral therapy before initiation of therapy for treatment of VTE
  • ^ Following appropriate treatment duration of DVT or PE treatment if used to reduce the risk of VTE recurrence
  • # May only use granules for suspension
  • ! May use granules for suspension or oral tablets