fondaparinux
selective factor Xa inhibitor· Brands: ArixtraSC
Mechanism of action
Fondaparinux is a synthetic pentasaccharide that binds to antithrombin III, causing a conformational change that increases antithrombin's ability to neutralise factor Xa. This enhanced inhibition of factor Xa interrupts the coagulation cascade, reducing thrombin generation and preventing thrombus formation. It has no direct action on thrombin itself and does not inhibit clot-bound factor Xa.
Pharmacokinetics
Fondaparinux is administered subcutaneously and is rapidly and completely absorbed, with a bioavailability approaching 100% and peak plasma concentrations occurring 2 to 3 hours after dosing. It is not metabolised and is excreted unchanged primarily in the urine, with a terminal half-life of approximately 17 to 21 hours in healthy individuals. It binds specifically to antithrombin and does not interact with other plasma proteins. Clearance is reduced in renal impairment, so dose adjustment or avoidance is required in patients with creatinine clearance below 30 mL/min.
Indications & dosing
VTE prophylaxis after major orthopedic surgery (hip fracture, elective hip replacement, knee replacement)
First dose 6-8 hours after surgery, once haemostasis achieved. Duration: 5-9 weeks after hip fracture, 5 weeks after hip replacement, 2 weeks after knee replacement.
- adult · SC: 2.5 mg once daily · First dose 6-8 hours after surgery, once haemostasis achieved. Duration: 5-9 weeks after hip fracture, 5 weeks after hip replacement, 2 weeks after knee replacement.
Treatment of deep-vein thrombosis and pulmonary embolism in patients weighing <50 kg
Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
- adult · SC: 5 mg once daily · Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
Treatment of deep-vein thrombosis and pulmonary embolism in patients weighing 50-100 kg
Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
- adult · SC: 7.5 mg once daily · Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
Treatment of deep-vein thrombosis and pulmonary embolism in patients weighing >100 kg
Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
- adult · SC: 10 mg once daily · Administer with a vitamin K antagonist (e.g. warfarin) for at least 5 days, or until INR ≥2.0 for 24 hours.
Acute coronary syndromes (unstable angina, non-ST segment elevation MI, ST segment elevation MI)
Used in addition to standard therapy. Duration up to 8 days, or until revascularisation. Practice varies; check local formulary.
- adult · SC: 2.5 mg once daily · Used in addition to standard therapy. Duration up to 8 days, or until revascularisation. Practice varies; check local formulary.
Contraindications & precautions
- Active major bleeding · Fondaparinux is contraindicated in patients with active, clinically significant bleeding because it increases the risk of further haemorrhage.
- Severe renal impairment (creatinine clearance < 30 mL/min) · Fondaparinux is primarily eliminated via the kidneys; its accumulation in severe renal impairment increases bleeding risk.
- Hypersensitivity to fondaparinux or its excipients · Anaphylactic reactions have been reported. Patients with known hypersensitivity should not receive the drug.
- Bacterial endocarditis · Anticoagulation in patients with bacterial endocarditis may precipitate serious haemorrhagic complications.
- Monitor renal function periodically, particularly in patients at risk of renal impairment, and adjust or discontinue therapy if Creatinine Clearance falls below 30 mL/min.
- Use with caution in patients with increased risk of bleeding (e.g., congenital or acquired bleeding disorders, recent surgery, concurrent use of other anticoagulants).
- Avoid neuraxial anaesthesia or spinal puncture within 6-8 hours of fondaparinux administration to minimise the risk of spinal haematoma.
- Do not administer fondaparinux intramuscularly due to the risk of injection site haematoma.
Adverse effects
- Haemorrhageserious
- Thrombocytopeniaserious
- Injection site reactions (e.g., haematoma, pain)
- Anaemia
- Allergic reactions (e.g., rash, pruritus, anaphylaxis)serious
Renal & hepatic adjustment
- eGFR 0–30: Contraindicated in severe renal impairment (CrCl < 30 mL/min). (avoid)
- eGFR 30–50: Reduce dose: for VTE treatment, use 2.5 mg once daily; for prophylaxis, use 1.5 mg once daily. Monitor renal function regularly.
Monitoring, pregnancy & toxicity
- Serum creatinine and creatinine clearance · Baseline and periodically; more frequently if renal impairment
- Platelet count · Baseline and periodically; monitor for thrombocytopenia
- Signs of bleeding · During therapy
- Pregnancy: Not recommended as first-line in pregnancy; consider if LMWH is contraindicated (e.g., heparin-induced thrombocytopenia). Fondaparinux does not cross the placenta. Evaluate risk/benefit; specialist management advised.
- Toxicity: Bleeding · Withhold drug and provide supportive care. There is no specific antidote; for severe bleeding, consider prothrombin complex concentrate or recombinant factor VIIa. Protamine sulfate is ineffective.
Clinical notes
Fondaparinux is indicated for the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery of the lower limbs, and for the treatment of acute deep vein thrombosis or pulmonary embolism when used with a vitamin K antagonist or alone. It is also used for the treatment of unstable angina or non-ST-segment elevation myocardial infarction in some protocols. The dose is given once daily by subcutaneous injection; treatment doses are weight-based. Bleeding is the principal adverse effect, and platelet counts should be monitored to detect thrombocytopenia. It is contraindicated in severe renal impairment, active severe bleeding, bacterial endocarditis, or a history of heparin-induced thrombocytopenia. No specific antidote exists; in the event of major bleeding, prothrombin complex concentrate or recombinant factor VIIa may be considered.
Log in to read the full fondaparinux monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary