Note: This drug is not currently available in the US, Mexico, or Canada. I will update this web page when it becomes available. Please do not call as we are not doing any additional studies on this medication at this time.

In what I consider a stunning move, an FDA advisory committee ruled against Exanta® for approval in September 2004. This was apparently due to a theoretical concern of liver failure. I say theoretical because in the 3000 patients treated with this medication for over one year, exactly 0 of them got liver failure. All abnormal liver tests due to Exanta® returned to normal. I estimate there will be 1000-2500 more deaths next year and 11,000 major disabling strokes due to their decision and I feel my estimates are conservative. I believe the committee failed to recognize the real world situation when only about 50% of patients eligible for coumadin receive it due to difficulties in taking this medication. What follows is my previous web page article on this drug prior to the FDA advisory committee ruling.

Exanta® or Ximelagatran is a new oral anticoagulant. It is a small compound that is absorbed and converted to the active substance Melagatran. Melagatran can also be given by injection (as can a number of other anticoagulants). Exanta® interferes with thrombin which is the final step in the activation of the clotting pathway. This group of drugs is known as direct thrombin inhibitors. It will be the first oral direct thrombin inhibitor to be introduced to market

Oral anticoagulation has been hampered by the difficulties in using Coumadin® or Warfarin. Coumadin® interacts with many other medications. In addition, Coumadin® is a drug with a narrow therapeutic index (which means the dose has to be adjusted very exactly and individually for each patient in order to avoid adverse effects). There are several medications that interact with the Coumadin dosing as well. Because of this, many patients who would benefit from this medication cannot receive it because they are unwilling to have sufficiently close monitoring (monthly) or because the patient is judged incapable of handling a medication with potentially devastating consequences.

Exanta® does not have the same difficulties with dose adjustment or drug interaction as Coumadin® does. The presence of an injectable form will also be very useful when patients still need to be anticoagulated but are temporarily unable to take oral medication. In November of 2003, the US study of the prevention of stroke in atrial fibrillation (SPORTIF V) was released. 3,922 patients were enrolled and followed from 1 to 2 years. This study was double blinded meaning neither patient not treating physician knew which medication the patient was taking. The steps to maintain this blinding was elaborate with patients taking one real drug and one placebo medication. Patients on study drug still had their INR measured (the value to determine proper dosing of coumadin). A computer program generated faxed data that would force the physician to make adjustments from time to time as if the patient was on regular coumadin. Exanta® was associated with fewer strokes and systemic emboli (though not statistically significant) and less bleeding (statistically significant) than those patients who were on Coumadin.

The previously released Sportif III study, a European based study comparing randomized but unblinded Exanta to Coumadin in atrial fibrillation for the prevention of stroke, demonstrated Exanta to be superior to Coumadin in patients that actually took the medication (Lancet, Vol 362, Nov. 22, 2003, 1691-1698). It also caused fewer total bleeds although the number of major bleeding events were the same.The total number of deaths in the two groups was unchanged. There is clearly a small percentage of abnormal liver function test changes that warrants periodic monitoring.

The ease of use of this medication compared to coumadin (except potentially for patients with renal insufficiency) will probably lead to its rapid use once it is FDA approved. Dr. Johnson, an internist at the Diagnostic Clinic of Houston, will be happy to see patients who desire this medication once it is approved. You can call 713-797-9191 and ask for the appointment desk to make an appointment with him. The drug is currently not FDA approved.

A copy of the presentation of Sportif III given at the American College of Cardiology can be found on their website.

All anticoagulants increase the risk of bleeding and this risk must be weighed carefully against the potential benefits before prescribing this type of therapy.

Exanta has also been shown to reduce the risk of emboli from blood clots associated with knee surgery relative to coumadin. It has also been shown to reduce the risk of recurrent DVTs in patients with prior DVTs compared to placebo.