Adverse Effects

• Bleeding, elevated transaminases

Purpose
To provide details about fondaparinux use
 
Indication
Fondaparinux is now approved for the treatment of venous thromboembolism (VTE) in pediatric patients aged 1 year or older weighing at least 10 kg Currently, there are published pediatric clinical trials (FondaKIDS, FondaKIDS II, FondaKIDS III) with fondaparinux.
 
USE
 
Dosage Forms & Strengths
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
 
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
• Fondaparinux may be used in patients with a history of heparin-induced thrombocytopenia (HIT)

 
Pharmacokinetics

Half-life	17-21 h
Time to peak	2 to 3 h following subcutaneous injection
Excretion	Renal cleared

Dosing for Adults

• Acute coronary syndrome
  • 2.5 mg SC once daily for NSTEMI 
  • 2.5 mg IV x1, then start 2.5 mg SC once daily the following day
• DVT and PE treatment:
  • <50 kg: 5 mg SC once daily
  • 50 to 100 kg: 7.5 mg SC once daily
  • >100 kg: 10 mg SC once daily
• Heparin-induced thrombocytopenia
  • <50 kg: 5 mg SC once daily
  • 50 to 100 kg: 7.5 mg SC once daily
  • >100 kg: 10 mg SC once daily
• Superficial vein thrombosis, acute
  • 2.5 mg SC once daily
• VTE prophylaxis:
  • 2.5 mg SC once daily
    • Prophylactic use contraindicated in patients <50 kg undergoing hip fracture, hip replacement or knee replacement surgery, and abdominal surgery due to increased risk of bleeding.

Dosing for Pediatrics

• 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. 

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

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

 
Bleeding Precautions & Warnings

• While on anticoagulation avoid aspirin, ibuprofen, or other anti-platelet drugs unless specifically indicated as anti-platelet therapy.
• Avoid IM injections or lumbar punctures except in cases where benefits outweigh the risks. Avoid arterial punctures except in cases of emergencies. Apply pressure after venipuncture until bleeding has ceased.

Perioperative Management

• Decision making regarding whether fondaparinux needs to be held depends on type of surgery, renal function, and balance of bleeding versus thrombosis risk. If it is indicated, fondaparinux should be held 48-96 hours prior to procedures. May need to hold longer in patients with renal insufficiency.
• In rare cases, in patients with very high risk of thrombosis, bridging with unfractionated heparin may be required to limit the time off anticoagulation.
• Restart fondaparinux after the procedure as soon as adequate hemostasis has been established and once cleared by the surgeon or interventionalist. 

Reversal Information

• No reversal agent is currently available. May consider recombinant human coagulation Factor VIIa (rFVIIa, NovoSeven) 90 micrograms/kg IV for life-threatening bleeding (rVIIa will not affect anti-Xa activity and will not increase drug clearance).
• Critical site bleeds: Intracranial hemorrhage, including intraparenchymal, subdural, epidural, and subarachnoid hemorrhages; Other CNS hemorrhage, including intraocular, intra- or extra-axial spinal hemorrhages; Pericardial tamponade; Airway, including posterior epistaxis; Hemothorax, intraabdominal bleeding, and retroperitoneal hemorrhage; Extremity bleeds, including intramuscular and intraarticular bleeding concerning for compartment syndrome, bleeding associated with hemodynamic instability, bleeding in a noncompressible vessel (e.g., subclavian)

 
Transition Information

• See separate anticoagulant-specific Clinical Case Manual for transitioning from another specific anticoagulant to fondaparinux. 
• See table for switching from enoxaparin to another anticoagulant

From	To	Action
Fondaparinux	Argatroban/ Bivalirudin/ Dalteparin/ Enoxparin/ Heparin	From therapeutic fondaparinux: Initiate parenteral anticoagulant when next fondaparinux dose is expected to be given. In cases of high bleeding risk, consider omitting initial bolus when transitioning to heparin infusion. From prophylaxis fondaparinux: Initiate parenteral anticoagulant as clinically needed irrespective of time of last fondaparinux dose
	Apixaban, Betrixaban Dabigatran, Edoxaban, or Rivaroxaban	From therapeutic fondaparinux: Initiate when next fondaparinux dose is expected to be given. From prophylaxis fondaparinux: Initiate as clinically indicated irrespective of time of fondaparinux dose.
	Warfarin	From therapeutic fondaparinux: Overlap therapeutic dose fondaparinux with warfarin for at least 5 days AND until INR is in therapeutic range for at least 24 hours. From prophylaxis fondaparinux AND assuming patient does not have a new thrombosis: Initiate warfarin as clinically indicated irrespective of time of fondaparinux dose

Pregnancy
Currently, only Lovenox (enoxaparin) and unfractionated heparin are advised for use in pregnant women. The use of fondaparinux has been reported as a safe and effective alternative for heparin-intolerance pregnant women (e.g., severe allergic reaction to heparin, HIT, and who cannot receive danaparoid).

Patient Education & Ongoing Management
Discharging IHTC physician/APP is responsible for ensuring adequate follow-up for anticoagulation management has been scheduled prior to patient leaving the hospital.

References

1.     Arixtra (fondaparinux sodium) injection [Prescribing Information]. Research Triangle Park, North Carolina, GlaxoSmithKline; 2020.

2.     Monagle, P.; Chan, A.K.C.; Goldenberg, N.A.; Ichord, R.N.; Journeycake, J.M.; Nowak-Gottl, U.; and Vesely, S.K. Antithrombotic therapy in neonates and children: antithrombobotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. Chest, 2012: 141(2)(Suppl): e737se801s

3.     Fondaparinux. Lexi-Drugs AHFS Drug Information [Internet database]. Lexi-Comp, Inc.; Accessed October 5, 2023. 

4.     Young G, Yee DL, O’Brien SH, Khanna R, Barbour A, Nugent DJ. FondaKIDS: a prospective pharmacokinetic and safety study of fondaparinux in children between 1 and 18 years of age. Pediatr Blood Cancer. 2011;57:1049-1054

5.     Ko RH, Michieli C, Lira JL, Young G. FondaKIDS II: long-term followup data of children receiving fondaparinux for treatment of venous thromboembolic events. Thromb Res. 2014;134:643-647.

6. Shen X, Wile R, Young G. FondaKIDS III: A long-term retrospective cohort study of fondaparinux for treatment of venous thromboembolism in children. Pediatr Blood Cancer. 2020 Aug;67(8):e28295. doi: 10.1002/pbc.28295. Epub 2020 Apr 19. PMID: 32307822.

7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021345s052lbl.pdf