Exanta withdrawn from market worldwide, further studies halted

February 14, 2006

London, UK - AstraZeneca will no longer market or develop the oral anticoagulant ximelagatran (Exanta) because of "serious liver injury" observed in a study of venous-thromboembolism prophylaxis after orthopedic surgery, the company announced today. The trial had called for patients to take ximelagatran for up to 35 days, far beyond the 11-day limit currently in its labeling.

"This specific observation has not previously been made in relation to Exanta and indicates that regular liver-function monitoring may not mitigate the possible risk," according to an AstraZeneca press release. The company will halt two ongoing ximelagatran trials, and "regulatory files in orthopedic surgery and other indications in the US, Europe, and elsewhere will now be withdrawn."

As reported by heart wire , ximelagatran failed to gain market approval in the US in 2004 largely because of safety concerns, including evidence it may raise liver enzymes and several deaths from liver failure in clinical trials, and doubts about its effectiveness compared with warfarin.

The drug is currently marketed in Germany, Portugal, Sweden, Finland, Norway, Iceland, Austria, Denmark, France, Switzerland, Argentina, and Brazil, according to the company's statement, and approved but not on the market in Belgium, Spain, the Netherlands, Luxembourg, Greece, Indonesia, Hong Kong, Italy, Russia, and Ukraine.

For patients currently on ximelagatran, "doctors should consider changing treatment to an alternative anticoagulant while taking account of individual patient circumstances and ensuring uninterrupted anticoagulation," the company statement said. "The small number of current Exanta patients should be contacted by their doctor and reviewed promptly to avoid any unplanned discontinuation of therapy. AstraZeneca will maintain the supply of Exanta for a short period to allow doctors to manage patients during this transition."

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