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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/496403/2010

EMEA/H/C/000403

EPAR summary for the public

Arixtra

fondaparinux sodium

This document is a summary of the European public assessment report (EPAR) for Arixtra. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Arixtra.

What is Arixtra?

Arixtra is a solution for injection in a prefilled syringe. Arixtra contains the active substance fondaparinux sodium (1.5, 2.5, 5, 7.5 or 10 mg per syringe).

What is Arixtra used for?

Arixtra (1.5 and 2.5 mg strengths) is used to prevent venous thromboembolic events (VTEs, problems due to the formation of blood clots in the veins) in adults (aged 18 years or over) who are having major surgery to their legs, such as a hip or knee surgery. It can also be used in adults at high risk (because of their age or disease) when they are having abdominal surgery or are forced to stay in bed because of an acute illness.

Arixtra (1.5 and 2.5 mg strengths) is also used to treat adults who have blood clots in the superficial veins of the legs (superficial venous thrombosis) but not in their deep veins (deep vein thrombosis, DVT).

At higher strengths (5, 7.5 and 10 mg), Arixtra is used to treat DVT or pulmonary embolism (PE, clot in a blood vessel supplying the lungs).

The 2.5 mg strength is also used to treat adults with unstable angina (a type of chest pain that changes in severity due to reduced blood flow to the heart) or who are having a myocardial infarction (heart attack) with or without 'ST segment elevation' (an abnormal reading on the electrocardiogram or ECG).

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The medicine can only be obtained with a prescription.

How is Arixtra used?

In the prevention of VTEs, the recommended dose of Arixtra is 2.5 mg once a day by subcutaneous injection (under the skin). For patients having surgery, the first dose should be given six hours after the end of the operation. Treatment should be continued until the risk of VTE has been reduced, usually at least five to nine days after surgery. For patients who have kidney problems, Arixtra may not be suitable, or the 1.5-mg dose may be used.

In the treatment of superficial vein thrombosis, the recommended dose is 2.5 mg once a day by subcutaneous injection. Treatment should be started as soon as possible following exclusion of DVT, and should be continued for between 30 and 45 days.

In the treatment of DVT or PE, the recommended dose is 7.5 mg once a day by subcutaneous injection, usually for seven days. The dose may be adjusted depending on body weight.

For patients with unstable angina or myocardial infarction, the recommended dose is 2.5 mg once daily by subcutaneous injection, but the first dose is given intravenously (into a vein) through an existing line or as an infusion (drip) in patients with ST segment elevation. Treatment should be started as soon as possible after diagnosis and continued for up to eight days or until the patient is discharged from hospital. Arixtra is not recommended in patients who are about to undergo certain types of operations to unblock the heart's blood vessels.

For more information, see the summary of product characteristics (also part of the EPAR).

How does Arixtra work?

Blood clotting can be a problem when blood flow is disturbed in any way. Arixtra is an anticoagulant: it prevents the blood from coagulating (clotting). The active ingredient in Arixtra, fondaparinux sodium, stops one of the substances (factors) that are involved in the clotting of blood, factor Xa. When this is blocked, no thrombin (another factor) can be produced, and no clot can be formed. By using Arixtra after surgery, the risk of a blood clot forming is greatly reduced. By reducing blood clots, Arixtra can also help the flow of blood to the heart to be maintained in patients with angina or who are having a heart attack.

How has Arixtra been studied?

Arixtra has been studied for the prevention of and in the treatment of VTE. In the prevention studies, Arixtra was compared with other anticoagulants: enoxaparin (in hip or knee surgery; over 8,000 patients) or dalteparin (in abdominal surgery; 2,927 patients). It was also compared with placebo (a dummy treatment) when looking at patients with an acute illness (839 patients) and patients treated for an additional 24 days following hip fracture surgery (656 patients).In the treatment of VTE such as DVT and PE, Arixtra was compared with enoxaparin (DVT: 2,192 patients) or with unfractionated heparin (PE: 2,184 patients). In all studies, the main measure of effectiveness was the overall rate of thrombotic events (problems caused by blood clots).

In the treatment of superficial vein thrombosis, Arixtra was compared with placebo in one study of 3,000 patients with superficial vein thrombosis of the legs, without DVT. The main measure of effectiveness of this study was the overall occurrence of VTE or death.

Arixtra has also been studied in two main studies of patients with unstable angina or myocardial infarction. The first compared the effects of Arixtra with those of enoxaparin in over 20,000 patients with unstable angina or myocardial infarction without ST segment elevation, and the second compared Arixtra with standard care (unfractionated heparin in eligible patients, or placebo) in over 12,000 patients with myocardial infarction with ST segment elevation. The main measure of effectiveness was the proportion of patients who died or had an 'ischaemic event' (restriction of blood supply to an organ, including the heart).

What benefit has Arixtra shown during the studies?

Arixtra was at least as effective as the comparators in all of the studies that looked at the prevention of VTE and treatment of DVT and PE. The overall rate of thrombotic events in patients treated with Arixtra was significantly less than in patients treated with placebo or enoxaparin (for patients undergoing leg surgery), and was similar to that seen with enoxaparin (treatment of DVT), dalteparin or unfractionated heparin.

Arixtra was more effective than placebo in reducing the overall occurrence of VTE or death in patients with superficial vein thrombosis. While there was one VTE or death for every 100 patients taking Arixtra, there were six for every hundred taking placebo.

Arixtra was at least as effective as enoxaparin in preventing death or an ischaemic event in patients with unstable angina or myocardial infarction without ST segment elevation, with around 5% of the patients in each group had died or had an ischaemic event after nine days. In the study of myocardial infarction with ST segment elevation, Arixtra reduced the risk of death or another heart attack by 14% after 30 days, compared to standard care. However, these results were insufficient to show whether Arixtra was more effective than unfractionated heparin or not.

What is the risk associated with Arixtra?

As with other anticoagulant medicines, the most common side effect of Arixtra is bleeding. For the full list of all side effects reported with Arixtra, see the package leaflet.

Arixtra should not be used in people who may be hypersensitive (allergic) to fondaparinux sodium or any of the other ingredients, who might be bleeding already, who have acute bacterial endocarditis (an infection of the heart) or have severe kidney problems. For the full list of restrictions, see the package leaflet.

Why has Arixtra been approved?

The CHMP decided that Arixtra's benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Arixtra:

The European Commission granted a marketing authorisation valid throughout the European Union for Arixtra on 21 March 2002. The marketing authorisation is valid for an unlimited period. The marketing authorisation holder is Glaxo Group Ltd.

The full EPAR for Arixtra can be found here. For more information about treatment with Arixtra, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2010.

Arixtra

EMA/494080/2010

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