blood-clot

Apixaban is a new medication being developed for a variety of uses involving blood coagulation. Blood clotting is a serious problem that is extremely common and the existing anticoagulants have significant limitations.  Studies so far have shown that Apixaban is effective and safe, yet many details are still being worked out.

When you get surgery, say a knee replacement, something gynecological, or neurosurgery, you are at very high risk of developing a blood clot.  This is because the wound healing process may go awry and your risk of forming a blood clot can be as high as 60%.  The blood clot can block an artery or vein causing serious problems.

The current treatments to prevent this from happening have serious limitations.  Warfarin, one of the most widely used, is infamous for causing problems like excessive bleeding.  It also has a great deal of drug interactions.  Lovenox, another existing competitor, must be given by injection.

Apixaban has some very promising characteristics.  It is taken orally, is digested and absorbed by the body predictably, and seems to have minimal potential for drug-drug interactions.  It is being tested in Phase II and Phase III trials including tens of thousands of patients.

The initial studies into Apixaban have been as a prophylactic treatment to prevent venous thromboembolism (VTE) events after orthopedic surgery like knee replacement.  This is because of how high the risk for clotting is in those situations as well as the short time period of use.

So far they have been positive, showing that it has reduced risk of unwanted bleeding compared to existing treatment and similar efficacy.  It is highly likely that efficacy for that use will mean efficacy for other uses, like preventing clotting during atrial fibrillation.

A major Phase II trial of Apixaban to prevent VTE in 1238 patients after total knee replacement showed that it had lower VTE events as well as lower all cause mortality compared to Warfarin and Lovenox.

Another major study, ADVANCE-1, showed that Apixaban was roughly as effective as Lovenox in preventing serious adverse events.  The ADVANCE-II trial, on the other hand, showed that Apixaban was superior to once daily Lovenox.  In that study, 1.1% of patients on Apixaban had a VTE, compared to 2.2% on Loveonx.

Pharmacodynamics

Apixaban is relatively bioavailable and reaches peak levels 3 hours after dosing.  It has a half life of 12 hours.

25% of Apixaban is excreted through the kidneys and about 55% through the fecal route.  This is important as it indicates that issues like kidney impairment may not affect its use by the body too much.

Digestion of Apixaban in the liver is done through a combination of CYP3A4 and non CYP enzymatic processes.

New Drugs

If you want to learn about other new drugs, see here.

Sources:

1) Apixaban: an emerging oral factor Xa inhibitor
2) Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development
3) New oral anticoagulants: not quite there yet