e-DOX-a-ban

• Reduction of stroke/systemic embolization risk associated with nonvalvular atrial fibrillation (NVAF).
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5–10 days of initial therapy with a parenteral anticoagulant.

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

• Decreased thrombotic events associated with atrial fibrillation including stroke and systemic embolization.
• Resolution of DVT and PE.

Absorption: 62% absorbed following oral administration.

Distribution: Widely distributed to extravascular tissues.

Metabolism/Excretion: Minimal metabolism, one metabolite is pharmacologically active. Excreted mostly unchanged in urine.

Half-life: 10–14 hr.

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
• Triple — positive antiphospholipid syndrome (↑ risk of thrombosis)
• Lactation: Lactation.

Use Cautiously in:

• Elective/planned invasive/surgical procedures (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 for CCr 15–50 mL/min)
• Deteriorating or improving renal function (may require dose change)
• Body weight 60 kg (requires lower dose)
• Rep: Women of reproductive potential
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Safety and effectiveness not established in children.

GI: abnormal liver function tests.

Hemat: BLEEDING, anemia.

Drug-Drug:

• ↑risk of bleeding with other anticoagulants, aspirin, clopidogrel, ticagrelor, prasugrel, fibrinolytics, NSAIDs, SNRIs, or SSRIs.
• 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).

Treatment of NVAF

• PO (Adults): 60 mg once daily.

Treatment of DVT/PE

• PO (Adults >60 kg): 60 mg once daily.
• PO (Adults 60 kg or certain concurrent P-gp inhibitors): 30 mg once daily.

• 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.
• PO: Tablets may be crushed and mixed with 2–3 oz of water and immediately administered by mouth or through a gastric tube. May also mix with applesauce and administered immediately.
• If transitioning from warfarin 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.

Savaysa

Lixiana

Therapeutic Classification: anticoagulants

Pharmacologic Classification:

• Tablets: 15 mg; 30 mg; 60 mg;

(anticoagulant effect)

• Monitor for bleeding. Discontinue edoxaban if active 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. 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. May consider prothrombin complex concentrates (PCC), or other procoagulant reversal agents such as activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (rFVIIa). If PCC is used, monitoring anticoagulation effect of edoxaban using clotting test (PT, INR, or aPTT) or anti-FXa activity is not useful. 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.

• Assess creatinine clearance (CCr) using Cockcroft-Gault equation CCr = (140 - age) × (weight in kg) × (0.85 if female)/(72 × serum creatinine in mg/dL) before starting therapy.

• 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. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• 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.
• Rep: Advise female patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. May increase risk of uterine bleeding in females of reproductive potential and those with abnormal uterine bleeding. Monitor neonates for bleeding.

• Decreased thrombotic events (stroke and systemic embolization) associated with NVAF.
• Treatment of deep vein thrombosis DVT and pulmonary embolism PE.

NDC Code^*

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-07- 7 TABLET, FILM COATED in 1 BOTTLE (65597-201-07)

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-10- 10 TABLET, FILM COATED in 1 BLISTER PACK (65597-201-10)

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-30- 30 TABLET, FILM COATED in 1 BOTTLE (65597-201-30)

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-50- 500 TABLET, FILM COATED in 1 BOTTLE (65597-201-50)

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-70- 7 TABLET, FILM COATED in 1 BLISTER PACK (65597-201-70)

• 65597- Daiichi Sankyo Inc.
  • 65597-201- SAVAYSA
    • 65597-201-90- 90 TABLET, FILM COATED in 1 BOTTLE (65597-201-90)

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-05- 50 BLISTER PACK in 1 CARTON (65597-202-05) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-07- 7 TABLET, FILM COATED in 1 BOTTLE (65597-202-07)

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-10- 100 BLISTER PACK in 1 CARTON (65597-202-10) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-30- 30 TABLET, FILM COATED in 1 BOTTLE (65597-202-30)

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-50- 500 TABLET, FILM COATED in 1 BOTTLE (65597-202-50)

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-70- 7 TABLET, FILM COATED in 1 BLISTER PACK (65597-202-70)

• 65597- Daiichi Sankyo Inc.
  • 65597-202- SAVAYSA
    • 65597-202-90- 90 TABLET, FILM COATED in 1 BOTTLE (65597-202-90)

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-05- 50 BLISTER PACK in 1 CARTON (65597-203-05) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-07- 7 TABLET, FILM COATED in 1 BOTTLE (65597-203-07)

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-10- 100 BLISTER PACK in 1 CARTON (65597-203-10) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-30- 30 TABLET, FILM COATED in 1 BOTTLE (65597-203-30)

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-50- 500 TABLET, FILM COATED in 1 BOTTLE (65597-203-50)

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-70- 7 TABLET, FILM COATED in 1 BLISTER PACK (65597-203-70)

• 65597- Daiichi Sankyo Inc.
  • 65597-203- SAVAYSA
    • 65597-203-90- 90 TABLET, FILM COATED in 1 BOTTLE (65597-203-90)