The direct thrombin inhibitor melagatran/ximelagatran.
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.
Brighton
Timothy A
TA
Department of Haematology, St George Hospital, Gray Street, Kogarah, NSW 2217, Australia. t.brighton@unsw.edu.au
D000925:Anticoagulants / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001596:Benzylamines; D001777:Blood Coagulation / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy / Q000517:prevention & control; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy / Q000517:prevention & control; D013917:Thrombin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin; D005998:Glycine