Friday, January 28, 2011

Fondaparinux(Arixtra) and a word of caution

Fondaparinux is being used widely for anticoagulating patients in the acute setting (MI, PE,DVT etc). It has quite a few advantages over heparin and other low molecular weight heparins. Lets quickly see how it works.
Fondaparinux is a completely synthetic pentasaccharide. It is an indirect ,selective Factor Xa inhibitor. It inhibits factor Xa activity indirectly through binding and activating antithrombin III. Fondaparinux is not consumed in this reaction but instead is released from the inhibitory complex once binding of antithrombin III to factor Xa has occurred. In this way , by binding to 1 ATIII molecule,it can inhibit nearly 50 factor Xa molecules. It does not bind to other plasma proteins.predictable dose response that is independent of age or sex.It does not bind with platelet factor 4(PF4) , and hence doesnt cause thrombocytopenia (as caused by heparin- HIT).

Fondaparinux has nearly complete bioavailability after subcutaneous injection. The pharmacokinetics of fondaparinux appears predictable and consistent independent of age or sex. The peak plasma level is obtained about 2 h after the subcutaneous injection, indicating that a rapid onset of antithrombotic activity is obtained on initiation of treatment. The elimination half-life is about 17 h and it is dose-independent, which allows a convenient once-daily dosing regimen. Fondaparinux is eliminated exclusively by the kidneys.

This last property of being excreted by kidneys makes it a riskier agent in patients with renal failure...and it is contraindicated for patients with GFR < 30ml/hr(as risk of bleeding in this group is around 7.5%,compared to 0.1-0.4% in pts with GFR>80ml/hr). This is for patients with stable kidney function. A considerable proportion of patients for whom we prescribe Fondaparinux (until we confirm or refute the diagnosis of PE/DVT or NSTEMI) also have acute renal failure. In these instances the kidney's actual GFR is less than the reported GFR from the MDRD formula(as the production and excretion of creatinine is not in a steady state any more). So its possible to have a MDRD GFR as>30ml/min.....but with an actual GFR lot less than 30ml/ which case giving Fondaparinux might be a disaster (because of a 17hr half lasts for 2-4 days in normal individuals. looonger in pts with AKI!) It would be reasonable to first think twice..whether this patient needs acute anticoagulation...and if yes..then to consider unfractionated heparin in someone with acute renal failure. 


  1. Where did you get the figure for this entry? I would like to use it.