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Fondaparinux

Fondaparinux is a synthetic anticoagulant used to prevent and treat venous thromboembolism (VTE). It belongs to the class of selective Factor Xa inhibitors, offering targeted anticoagulation with predictable pharmacokinetics. This article provides a detailed overview of fondaparinux, including its mechanism of action, uses, dosage, side effects, precautions, drug interactions, and generic names, referencing the British National Formulary (BNF)Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology.

Fondaparinux exerts its anticoagulant effect by selectively binding to antithrombin III (ATIII), enhancing its ability to inactivate Factor Xa in the coagulation cascade. Unlike heparins, fondaparinux does not inhibit thrombin (Factor IIa) and has no direct effect on platelets, reducing the risk of heparin-induced thrombocytopenia (HIT). Its synthetic pentasaccharide structure ensures specificity for Factor Xa, leading to prolonged inhibition and sustained anticoagulation (Lippincott Textbook of Pharmacology).

Fondaparinux is approved for the following:

  1. Prevention of Venous Thromboembolism (VTE):
    • Post-surgical prophylaxis in patients undergoing hip fracture, knee replacement, or abdominal surgery (BNF).
  2. Treatment of Acute VTE:
    • Management of deep vein thrombosis (DVT) and pulmonary embolism (PE), often in combination with oral anticoagulants.
  3. Acute Coronary Syndromes (ACS):
    • Adjunctive therapy in unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) (Lange Basic & Clinical Pharmacology).

Dosage is weight-based and adjusted for renal function:

  1. Surgical Prophylaxis:
    • Adults: 2.5 mg subcutaneously once daily, starting 6 hours post-surgery.
    • Duration: 5–9 days for hip/knee surgery; up to 24 days for hip fracture surgery.
  2. Treatment of DVT/PE:
    • Adults <50 kg: 5 mg daily.
    • 50–100 kg: 7.5 mg daily.
    • >100 kg: 10 mg daily.
    • Renal Adjustment: Avoid if CrCl <30 mL/min; use caution in CrCl 30–50 mL/min (BNF).

Common and serious adverse effects include:

  • Bleeding: Major bleeding (e.g., gastrointestinal, intracranial).
  • Thrombocytopenia: Rare (unrelated to HIT).
  • Injection Site Reactions: Bruising, pain, or rash.
  • Anemia or Elevated Liver Enzymes (Lippincott Textbook of Pharmacology).
  • Contraindications: Severe renal impairment (CrCl <30 mL/min), active bleeding, bacterial endocarditis, hypersensitivity.
  • Warnings:
    • Avoid in patients <50 kg for DVT/PE treatment.
    • Monitor renal function regularly.
    • Risk of spinal/epidural hematoma with neuraxial anesthesia.
  • Pregnancy/Lactation: Use only if benefits outweigh risks; limited human data (BNF).
  • Anticoagulants/Antiplatelets (e.g., warfarin, aspirin): Increased bleeding risk.
  • NSAIDs (e.g., ibuprofen): Potentiate gastrointestinal bleeding.
  • Thrombolytics (e.g., alteplase): Avoid concurrent use.
    Fondaparinux has no CYP450 interactions, minimizing pharmacokinetic interactions (Lange Basic & Clinical Pharmacology).
  • Generic Name: Fondaparinux sodium.
  • Brand Name: Arixtra (available as prefilled syringes for subcutaneous injection).

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