New blood thinner offers first potential alternative in 50 years: ximelagatran.
Traditional anticoagulants employed in the treatment of thrombosis include the injectable heparins and oral warfarin. Though effective, these traditional agents are fraught with limitations in their ease of use in the clinical setting. Warfarin, for example, has many pharmacokinetic properties and food-and-drug interactions that result in unpredictable patient response and the need for expensive and time-consuming monitoring of coagulation status. Ximelagatran is a novel, promising, orally active, direct thrombin inhibitor currently in development that, for the first time in 50 years, offers a potential alternative to the mainstay oral agent "warfarin." Advantages of ximelagatran over warfarin include predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine anticoagulant monitoring, no clinically significant drug interactions, and fixed-dose administration. Ximelagatran has been evaluated for thromboprophylaxis following orthopedic surgery, acute treatment and secondary prevention of venous thrombosis, stroke prevention in atrial fibrillation, and acute coronary syndromes. Results of clinical trials suggest that ximelagatran is equally or more efficacious than warfarin and/or low-molecular-weight heparin therapy without increasing rates of minor or major bleeding. Although postmarketing surveillance will provide the final test of this drug, the future looks promising for addition of a new anticoagulant with the potential to provide excellent efficacy, predictable response, and reduced adverse effects. Pending regulatory approval, ximelagatran may help overcome barriers to appropriate anticoagulant therapy, thereby decreasing morbidity and mortality associated with thrombotic diseases.
Nutescu
Edith A
EA
Antithrombosis Service, Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, 60612, USA. enutescu@uic.edu
Helgason
Cathy M
CM
Briller
Joan
J
Schwertz
Dorie W
DW
D000284:Administration, Oral; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001596:Benzylamines; D001777:Blood Coagulation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003327:Coronary Disease / Q000517:prevention & control; D004334:Drug Administration Schedule; D017277:Drug Approval; D016903:Drug Monitoring; D006207:Half-Life; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019637:Orthopedic Procedures / Q000009:adverse effects; D011358:Product Surveillance, Postmarketing; D012449:Safety; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013927:Thrombosis / Q000188:drug therapy / Q000453:epidemiology; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran; D014859:Warfarin; D006493:Heparin