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. 2014 Apr;133(4):629-33.
doi: 10.1016/j.thromres.2013.11.019. Epub 2013 Nov 23.

Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency

Willie Hester  1 , Caitlyn Fry  2 , Daniel Gonzalez  3 , Michael Cohen-Wolkowiez  4 , Brant A Inman  5 , Thomas L Ortel  6
Affiliations

Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency

Willie Hester et al. Thromb Res. 2014 Apr.

Abstract

Fondaparinux is an antithrombin-dependent factor Xa inhibitor that is used for thromboprophylaxis of patients undergoing hip fracture surgery, hip or knee replacement, or abdominal surgery. It is cleared by the kidney and should be used with caution in patients with renal impairment and avoided in patients with severe renal insufficiency. Recently, several studies have demonstrated that a lower dose of fondaparinux in patients with moderate renal impairment appears to be safe and effective. The purpose of this study was to obtain pharmacokinetic and clinical data on the use of prophylactic fondaparinux in patients with renal insufficiency undergoing major abdominal surgery for cancer (n=8) or orthopedic surgery (n=1). Anti-factor Xa levels were obtained, and a published population pharmacokinetic model for fondaparinux was fit to the data. The data were analyzed using NONMEM software. Fondaparinux did not appear to accumulate in these patients, even when the drug was administered for up to twelve days. Pharmacokinetic analysis revealed that the apparent clearance in this population, who were primarily undergoing cancer surgery, was similar to prior studies in orthopedic surgery patients. In contrast, lower estimates were obtained for volume of distribution and absorption rate constant parameters. None of the patients sustained a hemorrhagic complication attributable to fondaparinux. One patient developed hypoxia in the setting of transient atrial fibrillation and clinical suspicion for pulmonary embolism, but this was not confirmed radiographically. These results support the use of 1.5mg of fondaparinux every 24hours for thromboprophylaxis in patients with renal insufficiency undergoing high-risk surgical procedures.

Keywords: Fondaparinux; Renal failure; Thromboprophylaxis.

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Conflict of interest statement

Conflict of Interest: TLO has received research support from Eisai, Pfizer, Daiichi Sankyo, and Instrumentation Laboratory, Inc, and has received consultation fees from Instrumentation Laboratory, Inc.

Figures

Figure 1
Figure 1
Observed versus individual model predicted fondaparinux concentrations.Anti-factor Xa levels vs. time are shown for all collected data points.For values less than 0.1 mcg/mL, half the limit of quantification (i.e., 0.05 mcg/mL) is plotted.
Figure 2
Figure 2
Relationship between creatinine clearance and the individual estimate for apparent clearance (CL/F).
See this image and copyright information in PMC

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