News from the World of Pharmacology
An Explosion of New AnticoagulantsThere has been a lot of activity in the anticoagulant arena over the past year. Dabigatran (Pradaxa®), approved in October 2010, became the first orally available anticoagulant contender to compete with age-old warfarin, at least in the atrial fibrillation market. While dabigatran, a direct thrombin inhibitor, offers some advantages over warfarin, such as more predictable pharmacology (ie., minimal potential for pharmacokinetic, life style or dietary interactions or genetic variability), easier dosing options and little or no need for monitoring in most patients, it is still far from the perfect oral anticoagulant. Stomach upset and the requirement for b.i.d dosing threaten compliance and, in this case, poor compliance can result in treatment failure and thrombotic events. Conversely, in the case where the anticoagulant causes hemorrhage, as all anticoagulants can do, there is no antidote to turn to, like vitamin K (warfarin) or protamine (heparin).
Enter Xarelto® (rivaroxaban), an oral Factor Xa inhibitor approved in July 2011 for prevention of DVT following orthopedic surgery. Much like Pradaxa, Xarelto has more predictable pharmacology than warfarin and no requirement for monitoring. One potential advantage it offers over Pradaxa is once daily dosing. It is also less likely to cause GI distress; that's a big plus for compliance. So far, so good, right? Not so fast. Xarelto, unlike Pradaxa, is cleared through the cytochrome P450 system (CYP3A4) and, therefore, the possibility for drug interactions could complicate therapy. There is also no specific antidote if hemorrhage occurs.
Both drugs are actively looking to compete with each other's currently approved indication: Pradaxa is looking for approval for prevention of DVT following orthopedic surgery (RE-NOVATE, RE-MODEL) and, just this week, Xarelto got a favorable nod from an FDA advisory committee for approval in the atrial fibrillation arena (ROCKET-AF). Of course, both would like to get approval across the board for everything thrombosis...........