Fondaparinux

Fondaparinux sodium injection is a Factor Xa inhibitor (anticoagulant) indicated for: • Prophylaxis of deep vein thrombosis (DVT) in adult patients undergoing hip fracture surgery (including extended prophylaxis), hip replacement surgery, knee replacement surgery, or abdominal surgery. • Treatment of DVT or acute pulmonary embolism (PE) in adult patients when administered in conjunction with warfarin sodium. • Treatment of venous thromboembolism (VTE) in pediatric patients aged 1 year or older weighing at least 10 kg.

The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, fondaparinux sodium potentiates (about 300 times) the innate neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. Fondaparinux sodium does not inactivate thrombin (activated Factor II) and has no known effect on platelet function. At the recommended dose, fondaparinux sodium does not affect fibrinolytic activity or bleeding time.

• For subcutaneous use, do not mix with other injections or infusions. • Prophylaxis of deep vein thrombosis in adults: Fondaparinux sodium injection 2.5 mg subcutaneously once daily after hemostasis has been established. The initial dose should be given no earlier than 6 hours to 8 hours after surgery and continued for 5 days to 9 days. For patients undergoing hip fracture surgery, extended prophylaxis up to 24 additional days is recommended. • Treatment of deep vein thrombosis and pulmonary embolism in adults: Fondaparinux sodium injection 5 mg (body weight less than 50 kg), 7.5 mg (50 kg to 100 kg), or 10 mg (greater than 100 kg) subcutaneously once daily. Treatment should continue for at least 5 days until INR 2 to 3 is achieved with warfarin sodium.

Fondaparinux sodium injection is contraindicated in the following conditions: • Severe renal impairment (creatinine clearance [CrCl] less than 30 mL/min). • 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 less than 50 kg (venous thromboembolism [VTE] prophylaxis in adults only). • History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to fondaparinux sodium.

Boxed 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. • Spinal or epidural hematomas, which may result in long-term or permanent paralysis, can occur. • Patients taking fondaparinux sodium with risk factors for bleeding are at increased risk of hemorrhage. • Bleeding risk is increased in renal impairment and in adult patients with low body weight less than 50 kg. • Thrombocytopenia can occur with administration of fondaparinux sodium.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Spinal or epidural hematomas • Hemorrhage • Renal impairment and bleeding risk • Body weight less than 50 kg and bleeding risk • Thrombocytopenia The most serious adverse reactions associated with the use of fondaparinux sodium are bleeding complications.

In clinical studies performed with fondaparinux sodium, the concomitant use of oral anticoagulants (warfarin sodium), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, fondaparinux sodium neither influenced the pharmacodynamics of warfarin sodium, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state. Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of therapy with fondaparinux sodium unless these agents are essential. If co-administration is necessary, monitor patients closely for hemorrhage. In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 micromolar i.e., 350 mg/L) was 17% to 28%.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).