Mechanism of Action

• Fondaparinux is a synthetic pentasaccharide that selectively binds to antithrombin, enhancing the inhibition of factor Xa exclusively, thereby preventing thrombin generation and clot formation

Pharmacokinetics

• Half-Life: 17-21 hours
• Metabolism: Renal cleared
• Time to peak: 2 to 3 h following subcutaneous injection

Dosing – Pediatric

• Approved for the treatment of venous thromboembolism (VTE) in pediatric patients aged 1 year or older weighing at least 10 kg
• Fondaparinux may be used in patients with a history of heparin-induced thrombocytopenia (HIT)

DVT treatment:

• 0.1 mg/kg/dose SC once daily. Refer to table below for rounding to syringe size.

Weight (Kg)	Fondaparinux dose (mg)
< 20	0.1 mg/kg (patient’s specific dose should be prepared according to label instructions)
20-40	2.5
40-60	5
60-100	7.5
>100	10
>175	Do not use/ no sufficient data

Whenever possible, patients weighing more than 20 kg should receive a full prefilled syringe for dosing. If therapeutic levels are not achievable using the prefilled syringe available strengths and dose adjustments are needed, a patient specific dose may be prepared. 

Initiating Therapy

• Prior to initiation of therapy or continuation of home therapy, but no longer than 48 hours before, the following labs should be checked: CBC, coagulation profile (PT, PTT, fibrinogen activity), CMP, urine pregnancy if applicable

Monitoring Therapy

• While FDA label recommends monitoring, Anti-Xa levels may not always be needed based on individual cases. If ordered, turn around time might be 3-5 days. 
• Situations that may warrant closer anti-Xa level monitoring:
  • Patients who are bleeding
  • Patients with abnormal renal function at initiation or decrease in renal function during therapy
  • Patients with concerns for outpatient medication adherence
• For monitoring fondaparinux anti-Xa levels, should use assay that is specifically calibrated for fondaparinux (send-out) with therapeutic goal range of ~0.5-1 mg/L.
  • If fondaparinux anti-Xa level <0.3 mg/L, increase dose by 0.03 mg/kg
  • If fondaparinux anti-Xa level 0.3 to 0.49 mg/L, increase dose by 0.01 mg/kg
  • If fondaparinux anti-Xa level 0.5 to 1 mg/L, keep same dose
  • If fondaparinux anti-Xa 1.1 to 1.1 mg/L, decrease dose by 0.01 mg/kg
  • If fondaparinux anti-Xa level >1.2 mg/L, decrease dose by 0.03 mg/kg
• Anti-Xa levels should be drawn from fresh venipuncture when possible. If drawn from heparinized line, waste should be drawn to avoid heparin contamination.
  • Levels may be underestimated in patients with very high levels of bilirubin or hemolysis.
  • Anti-factor Xa levels are checked 3-4 hours after a dose is administered. When starting therapy, check the anti-factor Xa level after the 2nd dose or 3rd dose, whichever occurs during the daytime. This can then be followed by weekly levels for a month, followed by less frequent measurements once levels are stable. For long-term patients, can check 1-3 times per year “these are the recommended intervals per FDA”.
  • Additional anti-factor Xa level titrations are checked in general 3 hours after the 2nd new dose until the patient has reached their targeted anticoagulation level.
  • Patients with pleural catheters for chylous drainage who have changing output should be monitored at least weekly.  
• CBC should be monitored while on fondaparinux during hospitalization

Dosage Forms

Single-dose, prefilled syringes containing 2.5 mg/0.5 mL (0.5 mL); 5 mg/0.4 mL (0.4 mL); 7.5 mg/0.6 mL (0.6 mL); 10 mg/0.8 mL (0.8 mL) of fondaparinux sodium

Administration
Fondaparinux should not be administered in areas where the skin is damaged/edematous. It is recommended to NOT use an insuflon catheter for the administration of fondaparinux given the risk of hematoma.
 
Safety Precautions

• Renal impairment: Dose adjustment needed for CrCl less than 50 mL/minute. Contraindicated for CrCl less than 30 mL/minute.
• Hepatic impairment: Use with caution in severe impairment.
• Drug-Drug interactions:
  • Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) may enhance the anticoagulant effect of Anticoagulants. 
• Drug-Food Interactions: None