Fondaparinux

Drug Information: Fondaparinux

Detailed information regarding Fondaparinux, a synthetic pentasaccharide anticoagulant medication. It works by selectively inhibiting Factor Xa, a key component of the coagulation cascade, preventing the formation of thrombin and ultimately reducing the risk of blood clot formation. It’s commonly used for the prophylaxis and treatment of venous thromboembolism and in the management of certain types of acute coronary syndromes.

Category

Anticoagulant

Mechanism of Action

Fondaparinux is a selective inhibitor of Factor Xa. Unlike heparin, which binds to antithrombin III (AT), enhancing AT’s activity against both Factor Xa and thrombin (Factor IIa), fondaparinux binds specifically to AT, causing a conformational change that dramatically increases AT’s neutralization of Factor Xa. This neutralization occurs through a stoichiometric interaction, meaning one molecule of fondaparinux-AT complex inactivates one molecule of Factor Xa. By inhibiting Factor Xa, fondaparinux indirectly reduces thrombin generation. Since thrombin is essential for fibrin clot formation and platelet activation, reducing thrombin levels inhibits coagulation. Fondaparinux, due to its selectivity, does *not* directly inhibit thrombin. The drug’s activity is primarily exerted by enhancing the inhibitory effect of antithrombin on Factor Xa, disrupting the coagulation cascade before thrombin formation, thereby preventing clot propagation and formation. Because fondaparinux dissociates from antithrombin after Factor Xa inhibition, it can be recycled to inhibit additional Factor Xa molecules, contributing to its prolonged anticoagulant effect.

Clinical Uses

Fondaparinux is primarily used for the prevention and treatment of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Specifically, it is used for prophylaxis of DVT following orthopedic surgeries such as hip fracture, hip replacement, and knee replacement, and abdominal surgery in patients at risk for thromboembolic complications. It is also indicated for the treatment of acute DVT and acute PE, often in conjunction with warfarin or other oral anticoagulants for long-term management. Additionally, fondaparinux is sometimes used in the management of acute coronary syndromes (ACS), particularly in patients undergoing percutaneous coronary intervention (PCI) as an alternative to heparin.

Dosage

Adult Dosage:

• Prophylaxis of DVT following surgery: 2.5 mg subcutaneously once daily, initiated 6-8 hours post-surgery. Duration varies based on surgical procedure.
• Treatment of DVT/PE: Weight-based dosing subcutaneously once daily:
  • <50 kg: 5 mg
  • 50-100 kg: 7.5 mg
  • >100 kg: 10 mg

Pediatric Dosage: Dosage in pediatric patients has not been well established and is generally not recommended. Consult a pediatric hematologist for guidance.
Route of Administration: Subcutaneous injection.

Indications

Common indications for Fondaparinux include:

• Prophylaxis of deep vein thrombosis (DVT) in patients undergoing major orthopedic surgery (hip fracture, hip replacement, knee replacement)
• Prophylaxis of DVT in abdominal surgery patients at risk of thromboembolic complications.
• Treatment of acute deep vein thrombosis (DVT)
• Treatment of acute pulmonary embolism (PE)
• Management of certain acute coronary syndromes (ACS)

Contraindications

Fondaparinux is contraindicated in the following conditions:

• Severe renal impairment (creatinine clearance <30 mL/min)
• Active major bleeding
• Thrombocytopenia associated with positive in vitro test for anti-platelet antibody in the presence of fondaparinux
• Bacterial endocarditis
• Weight less than 50 kg (treatment of DVT/PE)
• Known hypersensitivity to fondaparinux or any of its excipients

FAQ

1. What is Fondaparinux used for?

   Fondaparinux is an anticoagulant used to prevent and treat blood clots, specifically deep vein thrombosis (DVT) and pulmonary embolism (PE).

2. How does Fondaparinux work?

   It works by selectively inhibiting Factor Xa, a key protein involved in the blood clotting process, thereby preventing the formation of blood clots.

3. How is Fondaparinux administered?

   Fondaparinux is administered via subcutaneous injection.

4. What are the common side effects of Fondaparinux?

   Common side effects may include bleeding, injection site reactions (pain, bruising), and anemia.

5. Can Fondaparinux be used during pregnancy?

   The use of Fondaparinux during pregnancy should be carefully considered, weighing the risks and benefits. Consult with a healthcare professional.

6. What should I do if I miss a dose of Fondaparinux?

   If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not double the dose to catch up.

7. Are there any foods or medications I should avoid while taking Fondaparinux?

   Avoid taking medications that can increase the risk of bleeding, such as aspirin, NSAIDs (ibuprofen, naproxen), and other anticoagulants, unless directed by your doctor. Discuss all medications and supplements you are taking with your healthcare provider.

8. Is Fondaparinux safe for patients with kidney problems?

   Fondaparinux should be used with caution in patients with kidney problems. It is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min) due to the increased risk of bleeding.