References

1. Lovenox® [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2007.

2. Büller HR, Davidson BL, Decousus H, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004;140:867-873.

3. Büller HR, Davidson BL, Decousus H, et al; MATISSE Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med.
2003;349:1695-1702.

4. Turpie AG, Bauer KA, Eriksson BI, et al. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162:1833-1840.

5. Eriksson BI, Bauer KA, Lassen MR, et al; Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;345:1298-1304.

6. Bauer KA, Eriksson BI, Lassen MR, et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001;345:1305-1310.

7. Lassen MR, Bauer KA, Eriksson BI, et al. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomized double-blind comparison. Lancet. 2002;359:1715-1720.

8. Turpie AG, Bauer KA, Eriksson BI, et al. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hipreplacement surgery: a randomized double-blind trial. Lancet. 2002;359:1721-1726.

9. Surgical Care Improvement Project (SCIP) VTE-1 and VTE-2. Accessed September 19, 2007.

10. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(suppl 3):338S-400S.

11. Eriksson BI, Lassen MR; for the PENTasaccharide in HIp-FRActure Surgery Plus (PENTHIFRA Plus) Investigators. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2003;163:1337-1342.

12. Agnelli G, Bergqvist D, Cohen AT, et al; PEGASUS Investigators. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005;92:1212-1220.

13. Data on File, PEGASUS Study, GlaxoSmithKline.

14. Data on File, MATISSE DVT Study, GlaxoSmithKline.

15. Data on File, MATISSE PE Study, GlaxoSmithKline.

16. Petitou M, Lormeau JC, Choay J. Chemical synthesis of glycosaminoglycans: new approaches to antithrombotic drugs. Nature. 1991;350(suppl 6319):30-33.

17. Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 1: Heparin. American Heart Association. Circulation. 1994;89:1449-1468.

18. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest.
2001;119(suppl 1):64S-94S.

19. Nutescu EA, Helgason CM. Evolving concepts in the treatment of venous thromboembolism: the role of factor Xa inhibitors. Pharmacotherapy. 2004;24(7 Pt 2):82S-87S.

20. Weitz JI, Hirsh J. New anticoagulant drugs. Chest.
2001;119(suppl 1):95S-107S.

21. Hirsh J, Guyatt G, Albers GW, et al. Executive summary: American College of Chest Physicians evidence-based clinical practice guidelines 8th ed. Chest. 2008;133:71S–109S.

WARNING: SPINAL/EPIDURAL HEMATOMAS

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH), heparinoids, or fondaparinux sodium and are receiving neuraxial anesthesia or undergoing spinal puncture.

These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants
• a history of traumatic or repeated epidural or spinal puncture
• a history of spinal deformity or spinal surgery

Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary. Consider the benefit and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

INDICATIONS AND USAGE
Prophylaxis of Deep Vein Thrombosis
ARIXTRA is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing:

• hip fracture surgery, including extended prophylaxis;
• hip replacement surgery;
• knee replacement surgery;
• abdominal surgery who are at risk for thromboembolic complications.

Treatment of Acute Deep Vein Thrombosis
ARIXTRA is indicated for the treatment of acute deep vein thrombosis when administered in conjunction with warfarin sodium.

Treatment of Acute Pulmonary Embolism
ARIXTRA is indicated for the treatment of acute pulmonary embolism when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital.

CONTRAINDICATIONS
ARIXTRA is contraindicated in the following conditions:

• Severe renal impairment (creatinine clearance <30 mL/min) in prophylaxis or treatment of venous thromboembolism.
• Active major bleeding.
• Bacterial endocarditis.
• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.
• Body weight <50 kg (venous thromboembolism prophylaxis only).

WARNINGS AND PRECAUTIONS

• Use with caution in patients who have conditions or who are taking concomitant medications that increase risk of hemorrhage.
• Bleeding risk is increased in renal impairment and in patients with low body weight <50 kg.
• Thrombocytopenia can occur with administration of ARIXTRA.
• Periodic routine complete blood counts (including platelet counts), serum creatinine level, and stool occult blood tests are recommended.
• The packaging (needle guard) contains dry natural rubber and may cause allergic reactions in latex sensitive individuals.