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Edoxaban

Direct inhibitor of activated factor X with a rapid onset of action.

Trade names Lixiana, Savaysa

Administered orally once daily.

A reversible direct factor Xa inhibitior with linear and predictable pharmacokinetic profile.

62% oral bioavailability.

Half-life 10 to 14 hours.

Metabolism is minimal via hydrolysis.

Time to peak levels 1 to 2 hours after intake.

Renal elimination 50%.

Achieves maximum concentrations within one-two hours, and 50% excreted by the kidneys.

Patients with low bodyweight, moderate to severe renal dysfunction, with concomitant use of a P-glycoprotein inhibitor should have a dose reduction by 50%.

In a randomized double-blind noninferiority study patients with acute venous thromboembolism who had received initially heparin were randomized to receive Edoxaban 60 mg daily or 30 mg daily or to receive warfarin: patients received the study drugs for 3 to 12 months and Edoxaban was not inferior to standard care and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism including severe pulmonary embolus (Hokusai-VTE Investigators).

In a randomized, double-blind, double dummy trial comparing two once daily regimens of Edoxaban and warfarin in 21,105 patients with moderate to high-risk atrial fibrillation and the median follow-up of 2.8 years: primary efficacy endpoint stroke or systemic embolism-both once daily regimens were not inferior to waffling when respect to the prevention of stroke for systemic embolism and were associated with significant lower rates of bleeding and death from cardiovascular causes (ENGAGE AF-TIMI 48 Investigators).

In the above study the high dose of 60 mg of the Edoxaban regimen tends to be more effective than warfarin.

In the above study the incidence of hemorrhagic stroke and the rate of death from cardiovascular causes were significantly lower in the Edoxaban regimens than with warfarin.

Stroke prevention in nonvalvular atrial fibrillation is 60 mg orally daily but with creatinine clearance 15-50 mls per minute 30 mg orally daily.

In elderly Japanese patients with AF who were not appropriate candidates for standard oral anticoagulants, a once daily 15 mg dose of edoxaban was superior to placebo in preventing stroke with systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo (Akao K).

Postoperative thromboprophylaxis the drug is not yet approved.

Available as 15, 30, and 60 mg tablets.

Onset of action is 1 to 2 hours after administration.

Half-life 10 to 14 hours.

50% is excreted renally.

Creatinine clearance should be monitored, as changes in renal function may require a change in dosage or its discontinuation.

Metabolized by p-glycoprotein and is subject to drug interactions with P-glycoprotein inhibitors as with azithromycin, clarithromycin, Mason, verapmil, , quinidine, itraconazole, and ketocanazole, and inducers rifampin.

Does not have appreciable interactions with drugs metabolized the cytochrome P450.

Treatment of DVT/PE 60 mg daily or 30 mg daily if weight <60 kg and creatinine clearance 15-50 mls per minute.

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