Fondaparinux Sodium

Fondaparinux Sodium is a synthetic pentasaccharide anticoagulant that selectively inhibits factor Xa.

Approved Indications:

• Prevention of venous thromboembolism (VTE):
• In adult patients undergoing major orthopedic surgeries such as hip fracture surgery, hip replacement, or knee replacement.
• Treatment of acute deep vein thrombosis (DVT):
• In adult patients, with or without pulmonary embolism (PE).
• Treatment of acute pulmonary embolism (PE):
• As monotherapy in adults.

Off-label / Clinically Accepted Uses:

• Use in patients with heparin-induced thrombocytopenia (HIT) as an alternative anticoagulant.
• Prophylaxis of VTE in medically ill hospitalized patients with restricted mobility (investigational or institution-specific protocols).

Prevention of VTE (Orthopedic Surgery):

• Adult Dose: 2.5 mg subcutaneously once daily, starting 6–8 hours postoperatively, provided hemostasis is established.
• Duration: Typically 5–9 days post-knee replacement, up to 14 days post-hip replacement or fracture surgery.

Treatment of DVT and PE:

• Adult Dose: 7.5 mg subcutaneously once daily for patients weighing 50–100 kg.
• Weight-based adjustments:
• <50 kg: 5 mg once daily
• 100 kg: 10 mg once daily
• Duration: Typically 5–9 days initial therapy, followed by long-term anticoagulation as clinically indicated.

Special Populations:

• Renal impairment: Contraindicated in severe renal impairment (creatinine clearance <30 mL/min).
• Elderly: Dose adjustment not required but monitor renal function.
• Pediatrics: Safety and efficacy not established; generally not recommended.

Administration Route:

• Subcutaneous injection only.
• Do not administer intramuscularly or intravenously.

Fondaparinux Sodium selectively binds to antithrombin III, inducing a conformational change that enhances antithrombin’s inhibition of factor Xa. This prevents the conversion of prothrombin to thrombin, ultimately inhibiting fibrin clot formation. Unlike unfractionated heparin, Fondaparinux does not inhibit thrombin (factor IIa) directly, which provides a highly targeted anticoagulant effect with predictable pharmacokinetics and a lower risk of heparin-induced thrombocytopenia.

• Absorption: Complete bioavailability after subcutaneous injection; peak plasma concentrations within 2 hours.
• Distribution: Volume of distribution approximately 7–11 L; minimal plasma protein binding except to antithrombin III.
• Metabolism: Not metabolized by the liver; no significant biotransformation.
• Half-life: Approximately 17–21 hours; allows once-daily dosing.
• Elimination: Excreted unchanged via kidneys; renal clearance is proportional to creatinine clearance.
• Onset of action: Rapid, anticoagulant effect achieved within 1–3 hours post-injection.

• Pregnancy: Limited human data; animal studies show no teratogenicity at therapeutic doses. Use only if potential benefit justifies risk.
• Lactation: Fondaparinux is excreted minimally in breast milk; caution advised when administered to breastfeeding mothers.

• Primary Class: Anticoagulant
• Subclass: Synthetic selective factor Xa inhibitor (indirect)

• Known hypersensitivity to Fondaparinux or any component of the formulation.
• Active clinically significant bleeding.
• Severe renal impairment (creatinine clearance <30 mL/min).
• Bacterial endocarditis.
• Thrombocytopenia associated with positive test for anti-platelet antibodies in the presence of Fondaparinux.

• Bleeding risk: High-risk groups include elderly, low body weight, renal impairment, or concomitant use of antiplatelet/anticoagulant therapy.
• Spinal/epidural hematoma: Risk in patients undergoing neuraxial anesthesia or spinal puncture; monitor closely.
• Renal impairment: Contraindicated in severe renal dysfunction; dose not recommended for moderate impairment without monitoring.
• Surgical patients: Ensure adequate hemostasis prior to administration.
• Early detection of adverse events: Monitor for signs of bleeding (hematuria, hematoma, melena).

• Common:

  • Anemia, mild bleeding at injection site, bruising, headache, fever.

  Serious / Rare:

  • Major hemorrhage (gastrointestinal, intracranial, retroperitoneal).
  • Thrombocytopenia (rare).
  • Hypersensitivity reactions including anaphylaxis.

  Timing & Severity:

  • Adverse events often correlate with dose and renal function; bleeding may occur any time during therapy.

• Other anticoagulants (heparin, warfarin, DOACs): Increased risk of bleeding.
• Antiplatelet agents (aspirin, clopidogrel, NSAIDs): Increased bleeding risk.
• No significant CYP450 involvement: Minimal risk of metabolic interactions.
• Alcohol: May increase bleeding risk; caution advised.

• Current guidelines recommend Fondaparinux for VTE prophylaxis in high-risk orthopedic surgery patients and for treatment of acute DVT/PE.
• Highlighted as a preferred alternative in patients with heparin-induced thrombocytopenia.
• FDA and EMA updated labeling to emphasize renal function monitoring and weight-based dosing for treatment of DVT/PE.
• Use in pregnancy is restricted; benefit-risk assessment required.

• Store at 20°C to 25°C (room temperature) or refrigerated at 2°C to 8°C; protect from light.
• Keep in original packaging until use.
• Do not freeze.
• Prefilled syringes should be used immediately after removal from packaging; do not shake vigorously.