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FORMULARY FORUM

Fondaparinux for Prevention of Venous Thromboembolism in Major Orthopedic Surgery

at time of writing, Clinical Pharmacy Specialist, Cardiology, Harper University Hospital, Detroit Medical Center, Detroit, MI; Adjunct Assistant Professor, Eugene Applebaum College of Pharmacy and Allied Health Professions, Wayne State University, Detroit; Adjunct Clinical Assistant Professor, College of Pharmacy, University of Michigan, Ann Arbor; now, Senior Regional Medical Scientist for the Metabolic and Cardiovascular Unit, Glaxo-SmithKline, Philadelphia, PA

Garvin Lee, PharmD

PharmD, at time of writing, PharmD Student, College of Pharmacy and Allied Health Professions, University of Michigan

Reprints: Alison H Tran PharmD, 48224 Chesterfield Dr., Canton, MI 48187-1237, alison.h.tran{at}gsk.com

OBJECTIVE: To review clinical information related to fondaparinux, a synthetic pentasaccharide recently approved for the prevention of deep-vein thrombosis (DVT) in patients undergoing major orthopedic surgeries and for extended DVT prophylaxis after hip fracture surgery.

DATA SOURCES: Primary and review articles were identified by MEDLINE (1983-June 2003) using the key words pentasaccharide, Org31540, SR90107A, DVT prophylaxis, and fondaparinux. Additional sources were found listed in articles, abstracts, and unpublished data on file from the manufacturer. Articles selected were based on their coverage of the pharmacology, pharmacokinetics, safety, and efficacy of fondaparinux.

STUDY SELECTION AND DATA EXTRACTION: All of the articles identified were evaluated and all information deemed relevant was included.

DATA SYNTHESIS: Fondaparinux is a selective antithrombin-dependent, indirect inhibitor of activated factor Xa. It has a favorable and predictable pharmacokinetic profile when administered subcutaneously, and has a long half-life, allowing once-daily dosing. Fondaparinux lacks in vitro cross-reactivity with heparin-induced antibodies. Major Phase III studies have demonstrated that subcutaneous fondaparinux sodium 2.5 mg given at least 6 hours postoperatively resulted in a 55% reduction in the risk of venous thromboembolism (VTE) in patients undergoing hip fracture surgery, total hip replacement surgery, or knee replacement surgery compared with standard enoxaparin therapy. It has a safety profile similar to that of enoxaparin with respect to clinically relevant major bleeding, including fatal bleeding, nonfatal bleeding, and bleeding requiring repeat surgery. The use of fondaparinux for prolonged prophylaxis after hip fracture has demonstrated further reduction in VTE events without increasing the risk of bleeding.

CONCLUSIONS: Fondaparinux is the first of a new class of synthetic factor Xa inhibitors that demonstrated greater efficacy compared with enoxaparin for the prevention of VTE in major orthopedic surgery without an increase in clinically relevant bleeding. Given the favorable cost-effectiveness analysis and improved efficacy profile, fondaparinux should be considered for formulary addition for DVT prophylaxis in patients undergoing hip and knee replacement surgery. In patients undergoing hip fracture surgery, fondaparinux should be considered the DVT prophylaxis of choice. Extended thromboprophylaxis up to 28 days resulted in additional reduction in VTE (both symptomatic and venography-proven DVT) in patients with hip fracture surgery.

Key Words: deep-vein thrombosis prophylaxis, fondaparinux, Org31540/SR90107, pentasaccharide

Published Online, October 1, 2003. www.theannals.com, DOI 10.1345/aph.1C104

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-033-H01

This article has been cited by other articles:

				A. Rawat, T. T. Huynh, E. K. Peden, P. Kougias, and P. H. Lin Primary Prophylaxis of Venous Thromboembolism in Surgical Patients Vascular and Endovascular Surgery, June 1, 2008; 42(3): 205 - 216. [Abstract] [PDF]

				A. G. G. Turpie, B. I. Eriksson, K. A. Bauer, and M. R. Lassen Fondaparinux J. Am. Acad. Ortho. Surg., November 1, 2004; 12(6): 371 - 375. [Full Text] [PDF]