Edoxaban (Savaysa, Lixiana)

Indications

Systemic Embolism Prevention in Non-Valvular Atrial Fibrillation (see Atrial Fibrillation, [[Atrial Fibrillation]])

  • FDA Approval: Jan, 2015

Venous Thromboembolism-Deep Venous Thrombosis (DVT)/Acute Pulmonary Embolism (PE) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]] and Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])

  • FDA Approval: Jan, 2015

Pharmacology

Metabolism

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Administration

  • PO (Venous Thromboembolism): 5-10 days of parenteral anticoagulation, then 60 mg PO qday
    • Note: edoxaban/dabigatran require initial parenteral (heparin, etc) anticoagulation for the treatment of venous thromboembolism (see Dabigatran, [[Dabigatran]])
  • PO (Non-Valvular Atrial Fibrillation): 5-10 days of parenteral anticoagulation, then 60 mg PO qday
    • Note: edoxaban/dabigatran require initial parenteral (heparin, etc) anticoagulation for the treatment of venous thromboembolism (see Dabigatran, [[Dabigatran]])

Dose Adjustment

Hepatic

  • Mild Impairment (Child-Pugh Class A); no dose adjustment
  • Moderate-Severe Impairment (Child-Pugh Class B-C): avoid use

Renal

Venous Thromboembolism
  • CrCl ≥51 mL/min: No dosage adjustment recommended.
  • CrCl 15-50 mL/min: 30 mg PO qay
    • CrCl 30-50 mL/min (Beers Criteria for Patients ≥65 y/o): 30 mg PO qay
    • CrCl <30 mL/min (Beers Criteria for Patients ≥65 y/o): avoid use
  • CrCl <15 mL/min: avoid use
  • Hemodialysis: total edoxaban exposure is decreased by <7% during a 4-hour dialysis session
Non-Valvular Atrial Fibrillation
  • CrCl >95 mL/min: boxed warning regarding use in patients with atrial fibrillation -> avoid use
  • CrCl 51-95 mL/min: no dose adjustment
  • CrCl 15-50 mL/min: 30 mg PO qday
    • CrCl 30-50 mL/min (Beers Criteria for Patients ≥65 y/o): 30 mg PO qay
    • CrCl <30 mL/min (Beers Criteria for Patients ≥65 y/o): avoid use
  • CrCl <15 mL/min: avoid use
  • Hemodialysis: total edoxaban exposure is decreased by <7% during a 4-hour dialysis session

Effect on Anticoagulation Tests

Conversion to/from Edoxaban

Conversion from Edoxaban

  • Conversion to Parenteral Anticoagulant: discontinue edoxaban and start the parenteral anticoagulant (unfractionated heparin drip/low molecular weight heparin) at the time the next dose of edoxaban would have been taken

Conversion to Edoxaban

  • Conversion from Unfractionated Heparin Drip: discontinue heparin drip and initiate edoxaban 4 hrs later
  • Conversion from Low Molecular Weight Heparin (Enoxaparin, Dalteparin, Tinzaparin): discontinue low molecular weight heparin and initiate edoxaban at the time of the next scheduled administration of low molecular weight heparin

Abrupt Discontinuation of Edoxaban

  • Premature Discontinuation of Edoxaban Can Increase the Risk of Ischemic Events: for this reason, if edoxaban is discontinued for any reason other than hemorrhage or completion of course of therapy, consideration of coverage with an alternative anticoagulant should be considered

Adverse Effects

Hemorrhagic Adverse Effects

Comparative Rates of Hemorrhage Between Coumadin and Novel Oral Anticoagulants

  • Systematic Review of Novel Oral Anticoagulants, As Compared to Coumadin (Ann Intern Med, 2012) [MEDLINE]: included chronic non-valvular atrial fibrillation trials (RE-LY Trial (2009): dabigatran, ARISTOTLE Trial (2011): apixaban, ROCKET AF Trial (2011): rivaroxaban) and venous thromboembolism trials (EINSTEIN-DVT (2010): rivaroxaban, RE-COVER (2009): dabigatran, EINSTEIN-PE (2012): rivaroxaban)
    • Decreased Risk of Fatal Bleeding, as Compared to Coumadin (RR, 0.60 [CI, 0.46 to 0.77])
    • Decreased Risk of Major Bleeding, as Compared to Coumadin (RR, 0.80 [CI, 0.63 to 1.01])
    • Increased Risk of Gastrointestinal Bleeding, as Compared to Coumadin (RR, 1.30 [CI, 0.97 to 1.73])
    • Increased Risk of Discontinuation Due to Adverse Events, as Compared to Coumadin (RR, 1.23 [CI, 1.05 to 1.44])
    • Bleeding Risk for New Oral Anticoagulants May Be Higher in Patients >75 y/o or Those Receiving Coumadin Who Have Good Control
  • Systematic Review/Meta-Analysis Comparing Rates of Hemorrhage of Novel Oral Anticoagulants vs Coumadin When Used in the Setting of Renal Insufficiency (Chest, 2016) [MEDLINE]
    • CrCl 50-80 mL/min: novel oral anticoagulants had a significantly decreased risk of major bleeding, as compared to coumadin
    • CrCl <50 mL/min: novel oral anticoagulants had a non-significantly decreased risk of major bleeding, as compared to coumadin
      • Apixaban had the lowest rate of major bleeding in this subgroup

Types of Hemorrhage

Other Adverse Effects

  • Ischemic Events following Premature Discontinuation: boxed warnings

References

  • Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review. Ann Intern Med. 2012 Dec 4;157(11):796-807 [MEDLINE]
  • New oral anticoagulants in the treatment of pulmonary embolism: efficacy, bleeding risk, and monitoring. Thrombosis 2013;2013:973710. doi: 10.1155/2013/973710 [MEDLINE]
  • Major Bleeding and Hemorrhagic Stroke with Direct Oral Anticoagulants in Patients with Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials. Chest. 2016,(): doi:10.1016/j.chest.2015.12.029 [MEDLINE]