Ximelagatran: A New Era in Oral Anticoagulation

Objective: To review the pharmacology, pharmacokinetics, and clinical trials of the oral direct thrombin inhibitor ximelagatran. Data Sources: All primary articles involving ximelagatran or its active form, melagatran, and indexed on MEDLINE or International Pharmaceutical Abstracts databases (1966–December 2002) were evaluated. Recent ximelagatran and melagatran abstracts were also obtained online from the American Society of Hematology at www.hematology.org/meeting/abstracts.cfm (2001 and 2002). Data Synthesis: Ximelagatran is an orally bioavailable prodrug of melagatran that directly blocks unbound thrombin and fibrin-bound thrombin. Ximelagatran displays predictable pharmacodynamic and pharmacokinetic properties with a linear dose–response relationship and low interpatient variability. These parameters allow fixed dosing of ximelagatran without routine coagulation monitoring. Ximelagatran has yet to be approved by the FDA; however, several major clinical trials have been completed. These clinical trials have revealed that an easier-to-manage ximelagatran regimen is at least as effective and has a similar safety profile as conventional therapy for prevention of venous thromboembolism (VTE). The results of studies with ximelagatran for treatment of VTE and prevention of thrombosis associated with atrial fibrillation are promising, but need further investigation. Conclusions: Ximelagatran possesses several advantages over warfarin including fixed dosing and the lack of coagulation monitoring, the absence of known diet or drug interactions, and a faster onset of action. Ximelagatran appears to be at least as effective as warfarin for prevention of VTE. Further research is needed with ximelagatran in the treatment of VTE and atrial fibrillation.