edoxaban


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edoxaban

(e-dox-a-ban),

Savaysa

(trade name)

Classification

Therapeutic: anticoagulants
Pharmacologic: factor xa inhibitors
Pregnancy Category: C

Indications

Reduction of stroke/systemic embolization (SE) risk associated with nonvalvular atrial fibrillation (NVAF).

Action

Selective inhibitor of factor Xa. Does not inhibit platelet aggregation directly, but does inhibit thrombin-induced platelet aggregation. Decreases thrombin generation and thrombus development.

Therapeutic effects

Decreased thrombotic events associated with atrial fibrillation including stroke and systemic embolization.
Treatment of deep vein thrombosis (DVT) and plumonary embolism (PE) after 5–10 days of parenteral anticoagulant.

Pharmacokinetics

Absorption: 62% absorbed following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Minimal metabolism, one metabolite is pharmacologically active. Excreted mostly unchanged in urine.
Half-life: 10–14 hr.

Time/action profile (anticoagulant effect)

ROUTEONSETPEAKDURATION
POunknown1–2 hr24 hr

Contraindications/Precautions

Contraindicated in: Active bleeding; CCr >95 mL/min (↓ effectiveness); Concurrent use of other anticoagulants or rifampin; Presence of mechanical heart valves or severe mitral stenosis; Moderate to severe hepatic impairment; Lactation: Discontinue edoxaban or discontinue breastfeeding.
Use Cautiously in: Elective/planned invasive/surgical procudures (discontinue at least 24 hr prior to ↓ risk of bleeding); Premature discontinuation (↑ risk of ischemic events); Neuroaxial anesthesia/spinal puncture (↑ risk of spinal/epidural hematoma and potential paralysis); Renal impairment (dose reduction required for CCr 15–50 mL/min); Deteriorating or improving renal function (may require dose change); Body weight ≤60 kg (requires lower dose); Obstetric: Use during pregnancy only if potential benefit outweighs potential risk to fetus; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Gastrointestinal

  • abnormal liver function tests

Hematologic

  • bleeding (life-threatening)
  • anemia

Interactions

Drug-Drug interaction

Concurrent use of other anticoagulants, antifibrotics, antiplatelet agents, aspirin, fibrinolytics, NSAIDs or SSRIs may ↑ risk of bleeding. Rifampin may ↓ blood levels and effectiveness and is contraindicated.Concurrent use of P-gp inhibitors including azithromycin, clarithromcyin, erythromycin, itraconazole (oral), ketoconazole oral), quinidine, or verapamil ↑ blood levels and the risk of bleeding (lower dose required).

Route/Dosage

Treatment of NVAF

Oral (Adults) 60 mg once daily.

Renal Impairment

Oral (Adults) CCr 15–50 mL/min—30 mg once daily.

Treatment of DVT/PE

Oral (Adults >60 kg) 60 mg once daily.
Oral (Adults ≤60 kg or certain concurrent P-gp inhibitors) 30 mg once daily.

Renal Impairment

Oral (Adults CCr 15–50 ml/min ) 30 mg once daily.

Availability

Tablets: 15 mg, 30 mg, 60 mg

Nursing implications

Nursing assessment

  • Monitor for bleeding. Discontinue edoxaban if active pathological bleeding occurs. Concomitant drugs (aspirin, other antiplatelet agents, other antithrombotic agents, fibrinolytic therapy, chronic use of NSAIDs) may increase risk of bleeding. Anticoagulant effects of edoxaban persist for about 24 hr after last dose; there is no established way to reverse anticoagulant effects. Anticoagulant effects cannot be reliably monitored with standard laboratory tests. No reversal agent is available; protamine sulfate, vitamin K, and tranexamic acid do not reverse anticoagulant activity. Hemodialysis does not significantly contribute to edoxaban clearance.
  • Monitor frequently for signs and symptoms of neurological impairment (numbness or weakness of legs, bowel, or bladder dysfunction, back pain, tingling, muscle weakness); if noted, urgent treatment is required. Intrathecal or epidural catheters should not be removed earlier than 12 hr after last dose of edoxaban. Next dose of edoxaban should not be given less than 2 hr after removal of catheter.
  • Lab Test Considerations: Assess creatinine clearance (CrCl) using Cockcroft-Gault equation (Cockcroft-Gault CrCl = (140-age) x (weight in kg) x (0.85 if female)/(72 x creatinine in mg/dL) before starting therapy.

Potential Nursing Diagnoses

Risk for injury (Adverse Reactions)

Implementation

  • Discontinue edoxaban at least 24 hr prior to invasive or surgical procedures; may increase risk of bleeding. Edoxaban may be restarted as soon as adequate hemostasis is established; time to onset of pharmacodynamic effect is 1–2 hr.
  • Oral: Nonvalvular Atrial Fibrillation: Administer 60 mg once daily without regard to food. Do not use in patients with CrCl >95 mL/min. If CrCl 15 to 50 mL/min, decrease dose to 30 mg once daily.
  • Deep Vein Thrombosis and Pulmonary Embolism: Administer 60 mg once daily without regard to food following 5 to 10 days of parenteral anticoagulant therapy. If CrCl 15 to 50 mL/min, patient weighs ≤60 kg, or patient taking concurrent verapamil, quinidine, azithromycin, clarithromycin, erythromycin, oral itraconazole or oral ketoconazole, decrease dose to 30 mg once daily.
  • If transitioning from warafarin or other vitamin K antagonists to edoxaban,discontinue warfarin and start edoxaban when INR ≤2.5. If transitioning from oral anticoagulants other than warfarin or other Vitamin K antagonists to edoxaban, discontinue current oral anticoagulant and start edoxaban at time of next scheduled dose of other oral anticoagulant. If transitioning from low molecular weight heparin (LMWH) to edoxaban, discontinue LMWH and start edoxaban at time of next scheduled administration of LMWH. If transitioning from unfractionated heparin to edoxaban, discontinue infusion and start edoxaban 4 hr later.
  • If transitioning from edoxaban to warfarin, Oral Option: For patients taking 60 mg of edoxaban, reduce dose to 30 mg and begin warfarin concomitantly. For patients taking 30 mg edoxaban, reduce dose to 15 mg and begin warfarin concomitantly. Measure INR at least weekly and just prior to daily dose of edoxaban to minimize influence of edoxaban on INR measurements. Once stable INR ≥2.0 achieved, discontinue edoxaban and continue warfarin. Parenteral Option:Discontinue edoxaban and administer a parenteral anticoagulant and warfarin at time of next scheduled edoxaban dose. Once stable INR ≥2.0 achieved, discontinue parenteral anticoagulant and continue warfarin. If transitioning from edoxaban to non-Vitamin-K Dependant Oral anticoagulant, discontinue edoxaban and start other oral anticoagulant at time of next dose of edoxaban. If transitioning from edoxaban to parenteral anticoagulant, discontinue edoxaban and start parenteral anticoagulant at time of next dose of edoxaban.

Patient/Family Teaching

  • Instruct patient to take edoxaban as directed. Take missed doses as soon as remembered on same day. Return to regular schedule next day. Do not double doses in one day. Do not discontinue without consulting health care professional; stopping may increase risk of stroke.
  • Caution patient that they may bleed more easily, longer, or bruise more easily during therapy. Advise patient to notify health care professional immediately if bleeding or a fall, especially with head injury, occurs.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially other aspirin or NSAIDs.
  • Advise patient to notify health care professional of therapy before surgery, medical, or dental procedures are scheduled.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected. Avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

  • Decreased thrombotic events (stroke and systemic embolization) associated with atrial fibrillation.
  • Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
References in periodicals archive ?
La mayoria de estudios realizados con estos medicamentos excluyo a pacientes con protesis mecanicas (22, 28, 35), siendo el estudio ENGAGE-AF usando edoxaban (30) el unico que incluyo pacientes portadores de bioprotesis; y los estudios ENGAGE-AF (30) y ROCKET-AF (22) a pacientes que hubieran sido sometidos a comisurotomia o plastia valvular.
Se realizo una busqueda de la literatura en Pubmed incluyendo los siguientes terminos: atrial fibrillation, rivaroxaban, dabigatran, edoxaban, apixaban, warfarin, intracranial haemorrhage, intracranial hemorrhages, major bleeding, hemorrhage, haemorrhage, bleeding, subarachnoid hemorrhage, cerebral hemorrhage, intracerebral hemorrhage, intraventricular hemorrhage, subdural hemorrhage y stroke.
Mitchell et al., "Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: Systematic review and network meta-analysis," PLoS ONE, vol.
The target-specific oral anticoagulants (TSOAC) were developed more recently, marketing convenience and potentially improving clinical outcomes for patients, and include dabigatran (Pradaxa[R]), rivaroxaban (Xarelto[R]), apixaban (Eliquis[R]) and, edoxaban (Savaysa[R]).
A key objective of this short review is to provide primary care clinicians with the confidence to manage patients with AF in need of anticoagulation, including the safe and appropriate use of the non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, rivaroxaban (approved in the EU, US and several other countries worldwide) and edoxaban (approved in the EU, US and Japan).
However, a third direct factor Xa inhibitor, edoxaban, was recently approved by the US Food and Drug Administration to (1) protect against systemic embolism and stroke in patients with nonvalvular atrial fibrillation, and (2) treat deep vein thrombosis and pulmonary embolism.
Due to the involvement of CYP3A4 in all of the NOACs except dabigatran, plasma concentrations of apixaban, edoxaban, and rivaroxaban can become elevated in the presence of strong inhibitors.These strong inhibitors include: ketoconazole, itraconazole, conivaptan,HIV protease inhibitors, and clarithromycin.There are other weaker inhibitors and inducers that were also examined by Mohrien, Oliphant, and Self (2013) in an excellent review of these important drug interactions.
Rivaroxaban, apixaban and edoxaban are very specific antagonists of activated factor Xa, which directly converts prothrombin to thrombin, thus leading to clot formation.
Informacion acerca de otro inhibidor directo del factor Xa edoxaban en pacientes con FA va a estar disponible al finalizar el estudio ENGAGE AF-TIMI 48, y una nueva era de anticoagulantes orales esta emergiendo en el tratamiento de los pacientes con FA (26,27).
Daiichi Sankyo files for approval of edoxaban to prevent blood clots
Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced results from ELIMINATE-AF, a prospective, randomized, open label, blinded endpoint evaluation (PROBE) design study assessing the safety and efficacy of uninterrupted oral, once-daily edoxaban (known by the brand name LIXIANA outside the US and SAVAYSA in the US) 60 mg versus uninterrupted vitamin K antagonists (VKA) in atrial fibrillation (AF) patients undergoing catheter ablation.
He sees additional upside from approval of Andexxa in patients requiring emergency surgery and acute major bleeding on additional anticoagulants, such as edoxaban and enoxaparin, creating a blockbuster opportunity.