Parenteral Indirect Factor Xa Inhibitor

Question 1

Fondaparinux – Parenteral Indirect Factor Xa Inhibitor
Classification & Structure:

Answer 1

• Synthetic pentasaccharide derived from a natural component of heparin.
  
  • Indirectly inhibits Factor Xa via antithrombin {antithrombin inhibits Xa}
  • Does not bind PF4 → very low risk of HIT.

Question 2

Mechanism of Action:

Answer 2

• Interrupts coagulation upstream of thrombin.
  
  • No direct thrombin inhibition → avoids rebound thrombin generation.

Question 3

Pharmacokinetics:

Answer 3

• Route: Subcutaneous injection (once daily).
  
  • Half-life: 17–21 hours.
  • Peak plasma levels: ~2 hours post-injection.
  • Bioavailability: High; not affected by vasopressor use (2011 study).
  • Elimination: Renal — clearance reduced in renal impairment.

Question 4

Monitoring:

Answer 4

• Routine monitoring not required.
  
  • Factor Xa activity can be used if needed.
  • PT, INR, and aPTT are not affected.

Question 5

Clinical Uses:

Answer 5

1. VTE prophylaxis in hospitalized medical and surgical patients:
   
   • RCTs: ~46.7% reduction in VTE with no increase in bleeding.
   • Meta-analysis: ~20% reduction in VTE-related mortality.
     2. Treatment of HIT:
   • Rarely causes HIT.
   • Useful nonheparin option for HIT patients.
     3. Acute Coronary Syndrome (ACS):
   • Shown to be effective in trials (with and without coronary angiography).
   • Not widely adopted in practice.

Question 6

Reversal

Answer 6

• No specific reversal agent.