Fondaparinux

Usage

Fondaparinux is prescribed for the prevention and treatment of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used in the treatment of acute coronary syndromes (ACS), including unstable angina and myocardial infarction (MI) with or without ST-segment elevation. It’s pharmacological classification is an anticoagulant, specifically a Factor Xa inhibitor. Fondaparinux works by selectively binding to antithrombin III, which enhances antithrombin III’s ability to inhibit Factor Xa. This interruption of the coagulation cascade prevents thrombin formation and thrombus development.

Alternate Names

The international nonproprietary name (INN) is fondaparinux sodium. A popular brand name is Arixtra.

How It Works

Pharmacodynamics: Fondaparinux selectively inhibits Factor Xa by binding to antithrombin III and potentiating its activity. It does not directly inhibit thrombin (Factor IIa) nor does it affect platelet function. Routine coagulation tests like aPTT, ACT, PT/INR are generally not clinically affected.

Pharmacokinetics: Fondaparinux is administered subcutaneously and has nearly complete bioavailability. Peak plasma concentrations are reached in approximately 2 hours. It has a half-life of 17-21 hours, which allows for once-daily dosing. Fondaparinux is primarily eliminated by the kidneys.

Mode of Action: Fondaparinux selectively binds to antithrombin III. This binding significantly increases antithrombin III’s ability to neutralize Factor Xa, thereby interrupting the coagulation cascade and preventing further clot formation.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Fondaparinux’s primary mechanism is selective Factor Xa inhibition via antithrombin III potentiation.

Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• VTE Prophylaxis (Surgical): 2.5 mg SC once daily, starting 6-8 hours post-op after hemostasis.
• VTE Treatment (DVT/PE):
  • <50 kg: 5 mg SC once daily
  • 50-100 kg: 7.5 mg SC once daily

  • 100 kg: 10 mg SC once daily

• ACS (UA/NSTEMI/STEMI): 2.5 mg SC (or IV for initial dose in STEMI) once daily.
• Superficial Vein Thrombosis: 2.5 mg SC once daily for 30-45 days.

Children:

Safety and efficacy not established in patients under 17. Limited data suggests dosing can be weight based (mg/kg).

Special Cases:

• Elderly Patients: Strict adherence to timing of the first dose is essential, especially in those ≥75 years, with low body weight, or renal impairment.
• Patients with Renal Impairment:
  • CrCl 20-30 mL/min: 1.5 mg daily or 2.5 mg every other day for VTE prophylaxis.
  • CrCl <20 mL/min: Contraindicated.
• Patients with Hepatic Dysfunction: No adjustment for mild to moderate impairment. Use with caution in severe impairment.
• Patients with Comorbid Conditions: Individualized assessment is needed, particularly in patients with a high bleeding risk.

Clinical Use Cases

• Surgical Procedures: Dosage as per VTE prophylaxis.
• Intubation, Mechanical Ventilation, ICU Use: Consider VTE prophylaxis or treatment based on individual risk assessment.
• Emergency Situations: Fondaparinux’s delayed onset of action makes it less suitable for emergencies requiring immediate anticoagulation.

Dosage Adjustments:

Dosage adjustments are primarily based on renal function and body weight. Close monitoring for bleeding is required in patients with renal impairment, hepatic dysfunction, or other risk factors for bleeding.

Side Effects

Common Side Effects:

Bleeding (e.g., bruising, bleeding gums, epistaxis), anemia, pain at injection site.

Rare but Serious Side Effects:

Major bleeding (e.g., intracranial hemorrhage, gastrointestinal bleeding), spinal/epidural hematoma (especially with neuraxial anesthesia), thrombocytopenia.

Long-Term Effects:

Osteoporosis with long-term use (rare).

Adverse Drug Reactions (ADR):

Severe bleeding, allergic reactions (rare), thrombocytopenia.

Contraindications

• Active major bleeding.
• Severe renal impairment (CrCl <20 mL/min).
• Bacterial endocarditis.
• Hypersensitivity to fondaparinux.

Drug Interactions

Drugs that increase bleeding risk (e.g., NSAIDs, aspirin, other anticoagulants, antiplatelet agents).

Pregnancy and Breastfeeding

Limited data suggest potential placental transfer. Use only if clearly needed. Breastfeeding is not recommended.

Drug Profile Summary

• Mechanism of Action: Selective Factor Xa inhibitor.
• Side Effects: Bleeding, anemia, injection site reactions.
• Contraindications: Active bleeding, severe renal impairment, hypersensitivity.
• Drug Interactions: Drugs that increase bleeding risk.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks. Not recommended while breastfeeding.
• Dosage: Variable depending on indication and patient factors.
• Monitoring Parameters: Signs of bleeding, hemoglobin, platelet count, renal function.

Popular Combinations

Fondaparinux is often used in conjunction with warfarin for VTE treatment, with warfarin initiated as soon as possible and fondaparinux continued for at least 5 days and until therapeutic INR is achieved.

Precautions

• General Precautions: Assess bleeding risk before initiating therapy. Monitor for signs of bleeding.
• Specific Populations: See dosage adjustments for renal and hepatic impairment, elderly patients, and pregnancy/breastfeeding.
• Lifestyle Considerations: Caution patients about activities that could increase bleeding risk.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Fondaparinux?

A: Dosage varies depending on the indication and patient-specific factors. See the detailed dosage section above.

Q2: How is Fondaparinux administered?

A: Subcutaneously, typically into the abdominal wall.

Q3: What is the mechanism of action of Fondaparinux?

A: Fondaparinux is a selective inhibitor of Factor Xa. It binds to antithrombin III, increasing its ability to inhibit Factor Xa, thereby disrupting the coagulation cascade.

Q4: What are the main side effects of Fondaparinux?

A: Bleeding is the most common side effect.

Q5: When is Fondaparinux contraindicated?

A: In patients with severe renal impairment (CrCl <20 mL/min), active major bleeding, or hypersensitivity to the drug.

Q6: Can Fondaparinux be used in pregnant or breastfeeding women?

A: Use with caution if benefits outweigh risks in pregnant women. Not recommended while breastfeeding.

Q7: What monitoring is required during Fondaparinux therapy?

A: Monitor for signs of bleeding, hemoglobin, platelet count, and renal function.

Q8: How does renal impairment affect Fondaparinux dosing?

A: Dose reductions or avoidance are necessary in moderate to severe renal impairment. See dosage section for specifics.

Q9: What should be done if a patient on Fondaparinux requires an urgent surgical procedure?

A: Discontinue Fondaparinux and consider bridging with another anticoagulant if appropriate, based on the patient’s bleeding and thrombotic risks.

Q10: Is Fondaparinux suitable for use in children?

A: Safety and efficacy have not been established in patients younger than 17.

Please note that this information is current as of February 16, 2025, and is intended for use by qualified medical professionals. Always consult the latest prescribing information and guidelines for the most up-to-date recommendations.