Ximelagatran

Uses

Ximelagatran was expected to replace heparin in many therapeutic settings, including deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke. The efficacy of ximelagatran for these indications had been well-documented (Eriksson et al 2003, Frances et al 2004, Schulman et al 2004).

An advantage, according to early reports by its manufacturer, was that it could be taken orally without any monitoring of its anticoagulant properties. This would have set it apart from protamine sulfate.

Side-effects

Ximelagatran was generally well tolerated in the trial populations, but a small proportion (5-6%) developed elevated liver enzyme levels, which prompted the FDA to reject an initial application for approval in 2004. The further development was discontinued in 2006 after it turned out hepatic damage could develop in the period subsequent to withdrawal of the drug. According to AstraZeneca, a chemically different but pharmacologically similar substance, AZD0837, is undergoing testing for similar indications (AstraZeneca press release 2006).

References

• AstraZeneca (February 14, 2006). "AstraZeneca Decides to Withdraw Exanta". Press release. Retrieved on 2006-05-08.
• Eriksson, H; Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S, THRIVE Investigators (January 2003). "A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I". Journal of Thrombosis and Haemostasis 1: 41–47. PMID 12871538. Retrieved on 2006-05-08.
• Francis, CW; Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr; EXULT A Study Group (October 2003). "Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement". New England Journal of Medicine 349 (18): 1703–1712. PMID 14585938. Retrieved on 2006-05-08.
• Schulman, S; Wåhlander K, Lundström T, Clason SB, Eriksson H, THRIVE III investigators (October 2003). "Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran". New England Journal of Medicine 349 (18): 1713–1721. PMID 14585939. Retrieved on 2006-05-08.
• Weitz, JI (August 2004). "New anticoagulants for treatment of venous thromboembolism". Circulation 110 (Suppl 1): 19–26. PMID 15339877. Retrieved on 2006-05-08.