The direct thrombin inhibitor melagatran/ximelagatran

Abstract

Melagatran is a synthetic, small-peptide direct thrombin inhibitor with anticoagulant activity. Ximelagatran, an oral prodrug, undergoes rapid enzymatic conversion to melagatran. Melagatran has rapid onset of action, fixed twice-daily dosing, stable absorption, apparent low potential for medication interactions, and no requirement for monitoring drug levels or dose adjustment. There is no specific antidote, but the drug has a short plasma elimination half-life (about 4 hours). In clinical studies, melagatran/ximelagatran is not inferior to warfarin for stroke prevention in patients with non-valvular atrial fibrillation, to heparin-warfarin for acute treatment and extended secondary prevention of deep vein thrombosis, and superior to warfarin for prevention of venous thromboembolism after major orthopaedic surgery. Major bleeding with melagatran/ximelagatran occurred at rates similar to those in patients treated with warfarin. 6%-12% of patients taking ximelagatran develop asymptomatic elevated liver enzyme levels (predominantly alanine aminotransferase) after 1-6 months of therapy; this usually resolves with cessation of therapy. Less than 1% of patients develop abnormal liver function while taking ximelagatran; this rarely persists or develops into clinical illness.