Ximelagatran

• ximelagatran is an oral direct thrombin inhibitor which is prescribed as a fixed dose to be taken twice daily
  • there is no clotting test yeat available to monitor the degree of anticoagulation achieved with ximlagatran; there is also no antidote
  • the half-life of ximelagatran is short; ximelagatran is renally excreted
  • trials have shown a similar bleeding rate between ximelagatran and warfarin
  • about 6% of patients taking ximelagatran have their liver alanine aminotransferase levels increased by more than a factor of two in the first few months of taking ximelagatran treatment
• there is evidence that, in patients with atrial fibrillation at risk of ischaemic stroke, ximelagatran was non-inferior to warfarin in preventing stroke and systemic embolism (2,3)
• in patients having total knee replacement, ximelagatran, 36mg twice daily, was more effective than warfarin in preventing venous thromboembolism (4)

In 2006, its manufacturer AstraZeneca announced that it would not attempt to market ximelagatran after reports of hepatotoxicity during trials. The distribution of ximelagatran was discontinued in countries where the drug had been approved.

Reference:

1. Pulse (2004), 64 (10), 80.
2. Olsson SB. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003;362:1691-8.
3. Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005;293:690-8.
4. Francis CW et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Eng J Med 2003;349:1703-12