Fondaparinux

Fondaparinux injection is approved for the following uses across its supported products (Arixtra and Fondaparinux Sodium):

• Prevention of DVT in adults after hip fracture surgery — including an extended course after the initial post-operative period
• Prevention of DVT in adults after hip replacement surgery
• Prevention of DVT in adults after knee replacement surgery
• Prevention of DVT in adults after abdominal surgery in patients at risk for clotting complications
• Treatment of acute DVT in adults — given alongside warfarin sodium
• Treatment of acute pulmonary embolism (PE) in adults — given alongside warfarin sodium when treatment starts in the hospital
• Treatment of venous thromboembolism (VTE) in children aged 1 year and older who weigh at least 10 kg

Fondaparinux is a Factor Xa inhibitor — it works by binding tightly to a natural protein in your blood called antithrombin III (ATIII). This binding supercharges ATIII's ability to neutralize Factor Xa, a key step in the clotting cascade, by about 300 times. Blocking Factor Xa stops the chain reaction that produces thrombin (the enzyme that turns fibrin into a solid clot), so new clots are much less likely to form or grow. Fondaparinux does not directly affect platelets and does not break down clots that have already formed.

Fondaparinux is injected subcutaneously (just under the skin) once daily. It can be taken with or without food since it is not swallowed. The dose and duration vary depending on whether it is being used for prevention after surgery or for treatment of an existing clot — your prescriber and the label on your medication will specify how long to continue. For surgical prevention, the first injection must be given no sooner than 6 to 8 hours after the operation; giving it earlier raises the risk of major bleeding. Do not mix fondaparinux with other medications, and discard any unused portion of the syringe.

The most common and clinically important side effect is bleeding. Other effects reported in clinical trials include:

• Anemia (low red blood cell count), especially after surgery
• Injection site reactions — bruising, rash, itching, or bleeding at the injection spot
• Insomnia (trouble sleeping)
• Dizziness
• Low potassium levels (hypokalemia)
• Nosebleeds
• Temporary, usually reversible rises in liver enzymes (AST/ALT)
• Skin blistering (bullous eruption) and purpura (small blood spots under the skin) have also been reported

Serious reactions requiring prompt medical attention include signs of internal bleeding, a sudden drop in platelet counts, spinal or epidural hematoma symptoms (back pain, leg weakness, or loss of bladder/bowel control), and signs of a severe allergic reaction such as swelling or difficulty breathing.

• Spinal/epidural hematoma (bleeding around the spinal cord): People receiving fondaparinux who also have spinal or epidural procedures face a risk of paralysis from bleeding around the spine. Risk is heightened by indwelling epidural catheters, use of NSAIDs or other anticoagulants, or a history of spinal surgery. Watch for back pain, leg numbness or weakness, or bladder/bowel problems — seek emergency care immediately if these occur.
• Bleeding risk: Fondaparinux increases the risk of bleeding in anyone, but especially in people with kidney problems, those weighing under 50 kg (adults), those with bleeding disorders, or those taking other blood thinners or NSAIDs. Do not give the first dose earlier than 6 to 8 hours after surgery.
• Kidney impairment: Fondaparinux is cleared by the kidneys. In severe kidney impairment (CrCl below 30 mL/min), the drug is contraindicated. In moderate impairment, it can linger longer and raise bleeding risk. Kidney function should be checked regularly during treatment.
• Thrombocytopenia (low platelets): A drop in platelet count can occur. If platelets fall below 100,000/mm³, fondaparinux must be stopped. Rare cases resembling heparin-induced thrombocytopenia have been reported.
• Latex allergy: The needle guard on the prefilled syringe contains dry natural rubber latex — alert your care team if you have a latex sensitivity.

Fondaparinux does not significantly affect the metabolism of most drugs, but certain combinations can raise the risk of serious bleeding:

• Other anticoagulants (e.g., warfarin, heparin, LMWHs) — used together intentionally in some cases, but require close monitoring; the combination significantly increases bleeding risk
• NSAIDs (e.g., ibuprofen, naproxen) — impair platelet function and can raise the risk of bleeding when used with fondaparinux
• Platelet inhibitors (e.g., aspirin, clopidogrel) — further increase bleeding risk; should be discontinued before starting fondaparinux unless essential
• Vitamin K antagonists (e.g., warfarin) — used together for DVT/PE treatment; INR must be monitored carefully
• Any agent affecting hemostasis (blood clotting) — should be stopped before fondaparinux is started if possible; if it must continue, monitor closely for signs of bleeding

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Severe kidney disease (CrCl below 30 mL/min): Fondaparinux is contraindicated — do not use
• Active major bleeding: Do not use fondaparinux
• Bacterial endocarditis (heart valve infection): Fondaparinux is contraindicated
• History of serious allergic reaction to fondaparinux (e.g., anaphylaxis, angioedema): Do not use
• Adults weighing less than 50 kg: Fondaparinux must not be used for DVT prophylaxis — bleeding risk is too high
• Thrombocytopenia with a positive anti-platelet antibody test in the presence of fondaparinux: Contraindicated
• Older adults: Higher risk of bleeding due to reduced kidney function; kidney function should be assessed before and during use
• Kidney or liver impairment: Increased bleeding risk; dose persistence is longer with kidney problems; use with caution
• Pregnancy: Fondaparinux crosses the placenta in small amounts; there is a risk of bleeding in the fetus and newborn; discuss risks and benefits with your doctor, especially as delivery approaches
• Breastfeeding: It is unknown whether fondaparinux passes into breast milk; discuss with your doctor
• Children under 1 year or weighing less than 10 kg: Safety and effectiveness have not been established
• Latex allergy: The prefilled syringe needle guard contains natural rubber latex

Taking too much fondaparinux can lead to serious bleeding complications. There is no specific antidote available for fondaparinux overdose. If overdose occurs, fondaparinux should be stopped right away and appropriate medical treatment initiated. Data suggest that hemodialysis (a kidney-filtering procedure) can increase fondaparinux clearance by about 20%, though this is not a standard reversal strategy.

Fondaparinux's blood-thinning activity is measured through its ability to inhibit Factor Xa — expressed in milligrams of fondaparinux rather than in heparin units, since standard heparin calibrators cannot be used. The drug's anti-Factor Xa activity rises with increasing blood concentration and reaches its peak level roughly 3 hours after injection. At recommended doses, fondaparinux does not affect platelet function, fibrinolytic (clot-dissolving) activity, or bleeding time.

When injected under the skin, fondaparinux is completely and rapidly absorbed — 100% of the dose reaches the bloodstream. It binds extensively (at least 94%) to antithrombin III in the blood and distributes mainly within the blood itself rather than spreading broadly into body tissues. Fondaparinux is not significantly broken down by the liver; most of it is eliminated unchanged through the urine. In people with normal kidney function, its half-life (the time for half the drug to leave the body) is 17 to 21 hours, which is why it is dosed once daily. In people with kidney impairment, the drug stays in the body longer and the anticoagulant effect can persist for 2 to 4 days or more after stopping.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) .