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Arixtra (fondaparinux sodium)


Conclusion

Arixtra is a synthetic pentasaccharide for the prevention of thromboembolic complications after major orthopaedic surgery such as knee or hip replacement operations. Arixtra has a significantly better effect than Klexane on the incidence of venous thromboembolic complications diagnosed by means of systematic venography. No difference in adverse drug effects has been demonstrated. Arixtra therapy costs about 1.5-2 times more than therapy with a low molecular weight heparin.

 

Background

A synthetic pentasaccharide, Arixtra (fondaparinux sodium) was marketed on Monday, 29 April 2002. The product is indicated for the prevention of deep-vein thrombosis (DVT) and thromboembolic complications in connection with major orthopaedic surgery on the lower extremities.

 

The recommended dose is 2.5 mg once daily administered by subcutaneous injection for five to nine days. The first dose should be given six hours after surgery, provided that haemostasis has been established.

 

According to the Danish Klaring report entitled Venøsthrombose profylakse fra 2000 (“Prevention of Venous Thrombosis in 2000 and Beyond”; in Danish only), half of these patients will develop DVT if left untreated. The Klaring report recommends that all patients who undergo major orthopaedic surgery on the pelvis or lower extremities are offered preventive treatment with a low molecular weight heparin (LMWH), possibly in combination with graded compression stockings.

 

Efficacy

There are currently four LMWHs on the market (see the table below). Arixtra has only been compared with enoxaparin (Klexane), in four controlled studies involving over 8000 patients.

 

Two European studies compared fondaparinux sodium 2.5 mg administered once daily starting 6-8 hours after surgery with enoxaparin 40 mg administered once daily starting 12 hours before surgery. Patients received the treatment for five to nine days. The incidence of thromboembolic complications detected by venography was evaluated up to day 11 after surgery. The incidence of both distal and proximal deep-vein thrombosis was significantly reduced in the fondaparinux sodium group (absolute risk reduction in the two studies was 5.1% and 10.8% respectively); there was no difference in incidence of symptomatic thromboembolic complications.

 

In the two other studies, 30 mg enoxaparin was administered postoperatively twice daily, which is the American dose regimen. However, these results support the conclusions of the first two studies. 

 

Adverse Drug Reactions

The most common adverse reactions were bleeding and clotting disorders, e.g. bleeding at the surgical site or thrombocytopenia, abnormal liver function tests and oedema.

 

In the above-mentioned studies, there was no significant difference between fondaparinux sodium and enoxaparin in the incidence of major bleeding (3.3% versus 2.6% in the two studies using the European dose regimen for enoxaparin).

 

Drug interactions

Caution is necessary in the administration of Arixtra together with other medicinal products which may increase the risk of bleeding. Arixtra has no influence on the INR activity of warfarin. Thus concomitant therapy with vitamin K antagonist may be administered if necessary. Heparins and fibrinolytic agents should not be used together with Arixtra.

 

Cost

According to the Danish Medicines Agency Price List (at 29 April 2002), Arixtra is roughly 1.5-2 times more expensive per treatment than Klexane and the other LMWHs. A pending pharmacoeconomic analysis will reveal whether lower costs due to fewer incidences of thromboembolic complications justify the product’s treatment price, which is substantially higher than that of Klexane.

 

High-risk dose  Preoperative dose  Postoperative dose  Cost per day  Cost per treatment
Arixtra (fondaparinux sodium)  2.5 mg once daily for 5-9 days  110.87  554.36 - 997.85
Clivarin (reviparin)  3436 IE 12 hours  3436 IE once daily for 7-10 days  41.10  328.76 – 452.05
Fragmin (dalteparin)  5000 IE 12 hours  5000 IE once daily for 5 days  49.19  ?295.11 -
Innohep (tinzaparin)  4500 IE 2 hours  4500 IE once daily for 7-10 days  48.78  390.24 – 536.58
Klexane (enoxaparin)  40 mg 12 hours  40 mg once daily for 7-10 days  45.35  362.80 - 498.85

 

 

Additional information is available from the European summary of product characteristics or at the Danish Medicines Agency Web site. 


Last modified: April 29th 2002


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