edoxaban (Rx)

Brand and Other Names:Savaysa
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 15mg
  • 30mg
  • 60mg

Stroke Prophylaxis with Atrial Fibrillation

Indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation (NVAF)

60 mg PO qDay

Limitation of use

  • CrCL >95 mL/min: Do not use; increased risk of ischemic stroke compared with warfarin in NVAF trial (see Black Box Warnings)

DVT or PE Treatment

Indicated for treatment of deep vein thrombosis (DVT) and pulmonary embolus (PE) in patients who have been initially treated with a parenteral anticoagulant for 5-10 days

>60 kg: 60 mg PO qDay

≤60 kg: 30 mg PO qDay

Dosage Modifications

Treatment of DVT/PE: Decrease dose to 30 mg PO qDay when coadministered with certain P-gp inhibitors (see Drug Interactions)

Renal impairment (NVAF)

  • CrCl >95 mL/min: Do not use; increased ischemic stroke compared with warfarin (see Black Box Warnings)
  • CrCl >50 to 95 mL/min: No dosage adjustment required
  • CrCl 15-50 mL/min: 30 mg PO qDay

Renal impairment (DVT/PE)

  • >50 mL/min: No dosage adjustment required
  • 15-50 mL/min: 30 mg PO qDay

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate-to-severe (Child-Pugh B/C): Not recommended; these patients have intrinsic coagulation abnormalities

Transition dosing to or from edoxaban

Transition to edoxaban

  • From warfarin or other vitamin K antagonists (VKAs): Discontinue warfarin and start edoxaban when INR ≤2.5
  • From oral anticoagulants other than warfarin or other VKAs: Discontinue current oral anticoagulant and initiate edoxaban at the time of the next scheduled dose of the previous oral anticoagulant
  • From low molecular weight heparin (LMWH): Discontinue LMWH and initiate edoxaban at the time of the next scheduled administration of LMWH
  • From unfractionated heparin: Discontinue heparin infusion and initiate edoxaban 4 hr later

Transition from edoxaban

  • To non-vitamin-K-dependent oral anticoagulants: Discontinue edoxaban and start the other oral anticoagulant at the time of the next dose of edoxaban
  • To parenteral anticoagulants: Discontinue edoxaban and start the parenteral anticoagulant at the time of the next dose of edoxaban
  • To warfarin (oral option)
    • If taking edoxaban 60 mg/day, reduce dose to 30 mg/day and begin warfarin concomitantly
    • If taking edoxaban 30 mg/day, reduce dose to 15 mg/day and begin warfarin concomitantly
    • INR must be measured at least weekly and just prior to the daily dose of edoxaban to minimize the influence on INR measurements
    • Once a stable INR ≥2.0 is achieved, discontinue edoxaban and continue warfarin
  • To warfarin (parenteral option)
    • Discontinue edoxaban and administer a parenteral anticoagulant and warfarin at the time of the next scheduled edoxaban dose
    • Once a stable INR ≥2.0 is achieved, discontinue the parenteral anticoagulant and continue warfarin

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and edoxaban

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            1-10% (ENGAGE AF-TIMI-48 study)

            Abnormal LFTs (4.8%)

            Rash (4.2%)

            1-10% (Hokusai VTE study)

            Abnormal LFTs (7.8%)

            Rash (3.6%)

            Anemia (1.7%)

            <1% (ENGAGE AF-TIMI-48 study)

            Interstitial lung disease (0.2%)

            Bleeding (ENGAGE AF-TIMI-48 study)

            Clinically relevant nonmajor bleeding (9.4%); warfarin (10.9%)

            Anemia-related adverse events (9.6%); warfarin (6.8%)

            Gastrointestinal bleeding

            • Major GI bleed (1.8%); warfarin (1.3%)
            • Upper GI (1.06%); warfarin (0.74%)
            • Lower GI (0.73%); warfarin (0.54%)
            • Severe, caused hemodynamic compromise requiring intervention (0.14%); warfarin (0.14%)
            • Fatal (<0.1%); warfarin (<0.1%)

            Major bleeding

            • Major (3.1%); warfarin (3.7%)
            • Intracranial (0.5%); warfarin (1%)
            • Type of intracranial bleeding
              • Hemorrhagic stroke (0.3%); warfarin (0.6%)
              • Other ICH (0.2%); warfarin (0.5%)

            Fatal bleeding

            • Fatal (1.8%); warfarin (0.4%)
            • ICH (0.2%); warfarin (0.4%)
            • Non-intracranial (<0.1%); warfarin (<0.1%)

            Bleeding (Hokusai VTE study)

            Any bleed (21.7%); warfarin (25.6%)

            Clinically relevant major bleeding (8.5%); warfarin (10.3%)

            Clinically relevant nonmajor bleeding (7.2%); warfarin (8.9%)

            Nonfatal, noncritical organ bleeding (1%); warfarin (0.8%)

            Decreased Hgb ≥2 g/dL (1%); warfarin (0.8%)

            Transfusion ≥2 units of RBC (0.7%); warfarin (0.5%)

            Major bleeding

            • Major (1.4%); warfarin (1.6%)
            • Fatal bleeding (<0.1%); warfarin (0.2%)
            • Intracranial, fatal (none); warfarin 0.1%)

            Critical organ bleeding

            • Nonfatal (0.3%); warfarin (0.6%)
            • Intracranial (0.1%); warfarin (0.3%)

            Bleeding ADRs

            • Vaginal (9%); warfarin (7.2%)
            • Cutaneous soft tissue (5.9%); warfarin (10%)
            • Epistaxis (4.7%); warfarin (5.7%)
            • GI bleed (4.2%); warfarin 3.6%)
            • Lower GI bleed (3.4%); warfarin (3.1%)
            • Oral/pharyngeal (3.4%); warfarin (3.9%)
            • Macroscopic hematuria/urethral (2.2%); warfarin (2.8%)
            • Puncture site (1.4%); warfarin (2.4%)
            Previous
            Next:

            Warnings

            Black Box Warnings

            Reduced efficacy with CrCl >95 mL/min

            • Do not use with CrCL >95 mL/min
            • In the ENGAGE AF-TIMI 48 study, patients with NVAF with CrCL >95 mL/min had an increased rate of ischemic stroke with edoxaban 60 mg/day compared with patients treated with warfarin
            • In these patients, another anticoagulant should be used

            Premature discontinuation increases risk for ischemic events

            • Premature discontinuation of any oral anticoagulant in the absence of adequate alternative anticoagulation increases the risk of ischemic events
            • If discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant as described in the transition guidance (see Adult Dosing)

            Spinal/epidural hematoma

            • Epidural or spinal hematomas may occur in patients treated with edoxaban who are receiving neuraxial anesthesia or undergoing spinal puncture
            • These hematomas may result in long-term or permanent paralysis; consider these risks when scheduling patients for spinal procedures
            • Monitor patients frequently for signs and symptoms of neurological impairment; if neurological compromise is noted, urgent treatment is necessary
            • Factors that can increase the risk of developing epidural or spinal hematomas in these patients include
              • use of indwelling epidural catheters
              • concomitant use of other drugs that affect hemostasis (eg, NSAIDs, platelet inhibitors, other anticoagulants, antithrombotic agents, fibrinolytic therapy, norepinephrine reuptake inhibitors)
              • history of traumatic or repeated epidural or spinal punctures
              • history of spinal deformity or spinal surgery
              • optimal timing between the administration of edoxaban and neuraxial procedures is not known

            Contraindications

            Active pathological bleeding

            Cautions

            Efficacy reduced in patients with nonvalvular atrial fibrillation (NVAF) with CrCl >95 mL/min (see Black Box Warnings)

            Increased risk of stroke with discontinuation in patients with NVAF (see Black Box Warnings)

            Do not use neuraxial anesthesia (spinal/epidural anesthesia) or spinal/epidural puncture; patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis (see Black Box Warnings)

            Increases the risk of bleeding and can cause serious and potentially fatal bleeding; promptly evaluate any signs or symptoms of blood loss; discontinue if patient experiences active pathological bleeding; concomitant drugs that affect coagulation can increase this risk

            Not recommended for patients with mechanical heart valves or moderate-to-severe mitral stenosis; safety and efficacy have not been established

            Coadministration with P-gp inhibitors

            • Edoxaban is a P-gp substrate; avoid coadministration with P-gp inducers (eg, rifampin)
            • NVAF: No dose reduction recommended when coadministered with P-gp inhibitors; based on clinical experience from the ENGAGE AF-TIMI 48 study, dose reduction in patients concomitantly receiving P-gp inhibitors resulted in edoxaban blood levels that were lower than in patients who were given the full dose
            • DVT/PE treatment: Dose reduction recommended when coadministered with P-gp inhibitors

            Reversal of anticoagulant effects

            • There is not established way to reverse anticoagulant effects od edoxaban
            • Effects may persist for 24 hr after the last dose
            • Anticoagulant effects cannot be reliably monitored with standard laboratory testing
            • Agent for edoxaban is not available; hemodialysis does not significantly contribute to edoxaban clearance
            • Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of edoxaban; the use of prothrombin complex concentrates, or other procoagulant reversal agents such as activated prothrombin complex concentrate or recombinant factor VIIa (rFVIIa) may be considered but has not been evaluated in clinical outcome studies; when PCCs are used, monitoring for anticoagulation effect of edoxaban using clotting test or anti-FXa activity is not useful and not recommended
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Available data about use in pregnant women are insufficient to determine whether there are drug-associated risks for adverse developmental outcomes; in animal developmental studies, no adverse developmental effects were seen when administered orally to pregnant rats and rabbits during organogenesis at up to 16-times and 8-times, respectively, the human exposure, when based on body surface area and AUC, respectively

            Pregnancy confers an increased risk of thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions; published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy

            Use may increase risk of bleeding in fetus and neonate; monitor neonates for bleeding

            Labor or delivery

            • All patients receiving anticoagulants, including pregnant women, are at risk for bleeding; use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas; consider use of a shorter acting anticoagulant as delivery approaches

            Lactation

            There are no data on presence in human milk, or effects on breastfeeding infant or on milk production; drug was present in rat milk; because of potential for serious adverse reactions in nursing infants, including hemorrhage, advise patients that breastfeeding is not recommended during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Factor Xa (FXa) inhibitor; inhibits platelet activation by selectively and reversibly blocking the active site of FXa without requiring a cofactor (eg, antithrombin III) for activity

            Inhibits free FXa, prothrombinase activity, and thrombin-induced platelet aggregation

            Inhibition of FXa in the coagulation cascade reduces thrombin generation and reduces thrombus formation

            Absorption

            Bioavailability: 62%

            Peak plasma concentration: 1-2 hr

            Food does not affect total systemic exposure

            Substrate of P-gp transporter

            Distribution

            Disposition is biphasic

            Steady-state reached: 3 days

            Vd (steady-state): 107 L

            Protein bound: 55%

            Metabolism

            Unchanged edoxaban is the predominant form in plasma

            Minimal metabolism via hydrolysis (mediated by carboxylesterase 1), conjugation, and oxidation by CYP3A4

            <10% is hydrolyzed to the predominant metabolite M-4

            Exposure to other metabolites is <5%

            Elimination

            Half-life: 10-14 hr

            Renal clearance: 11 L/hr

            Total clearance: 22 L/hr

            Excretion: Primarily as unchanged drug in urine; metabolism and biliary/intestinal excretion account for the remaining clearance

            Hemodialysis: 4 hr hemodialysis session reduced total edoxaban exposure by <7%

            Previous
            Next:

            Administration

            Instructions

            May take with or without food

            No data are available regarding the bioavailability upon crushing and/or mixing of edoxaban tablets into food, liquids, or administration through feeding tubes

            Discontinuation before surgery/interventions and then restarting

            • Discontinue at least 24 hr before invasive or surgical procedures because of the risk of bleeding
            • If surgery cannot be delayed, there is an increased risk of bleeding; risk of bleeding should be weighed against the urgency of intervention
            • Can be restarted after the surgical or other procedure as soon as adequate hemostasis has been established, noting that the time to onset of pharmacodynamic effect is 1-2 hr
            • Administer a parenteral anticoagulant and then switch to oral edoxaban, if oral medication cannot be taken during or after surgical intervention

            Missed dose

            • Take as soon as possible on the same day; resume normal dosing schedule on the next day
            • Do not double the dose to make up for a missed dose
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.