(2005-07-24)
GlaxoSmithKline plc announced today that the European Commission (EC) has approved ARIXTRA® (fondaparinux sodium) for prevention of venous thromboembolic events (VTE) in patients undergoing abdominal surgery who are judged to be at high risk of thromboembolic complications, such as patients undergoing abdominal cancer surgery.
“Because many patients undergoing abdominal surgery are judged to be at high risk of developing VTE, this new indication for Arixtra represents an important and exciting medical development for patients,” said Andrew Witty, president of GlaxoSmithKline Pharmaceuticals Europe. “Patients in the EU who are judged to be at high risk of thromboembolic complications during abdominal surgery, especially those with cancer, can now benefit from VTE protection with once-a-day ARIXTRA.”
The EC's decision was based on the results of the PEntasaccharide GenerAl SUrgery Study (PEGASUS). This study demonstrated that ARIXTRA is at least as effective as dalteparin in reducing the risk of total VTE: 4.6 percent of patients on ARIXTRA experienced a VTE versus 6.1 percent of patients on dalteparin.1 In the large subgroup of patients undergoing cancer surgery, representing 69 percent of the patient population, 4.7 percent of ARIXTRA patients experienced a VTE versus 7.7 percent in the dalteparin group.1
PEGASUS
PEGASUS was a double-blind study performed in 131 centers in 22 countries. A total of 2,927 patients were randomised to receive ARIXTRA 2.5 mg once daily or dalteparin 5000 IU once daily (2500 IU administered as a pre-operative and first post-operative dose) for 7+2 days.1 Sixty-nine percent of the patients underwent surgery for cancer.1 The primary safety outcome was major bleeding, which was observed in 3.4 percent of the patients in the ARIXTRA group and in 2.4 percent of the dalteparin group.1 The primary efficacy endpoint was the incidence of adjudicated VTE, evaluated up to Day 10, and was 4.6 percent for ARIXTRA and 6.1 percent for dalteparin, demonstrating that ARIXTRA is at least as effective as dalteparin.1 Secondary efficacy endpoints included symptomatic VTE, found to be similar between both treatment groups: 0.4 percent in the ARIXTRA group versus 0.3 percent in the dalteparin group.2
ARIXTRA
ARIXTRA is an anti-thrombotic agent already approved for use in the European Union (EU) for the prophylaxis of VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing surgery for hip fracture (including extended prophylaxis), knee replacement, and hip replacement, and acutely ill medical patients.2 Additionally, ARIXTRA is indicated for the treatment of acute DVT and the treatment of acute PE, except in haemodynamically unstable patients who require thrombolysis or pulmonary embolectomy.2
ARIXTRA is the first selective inhibitor of Factor Xa, a central protein in the coagulation process.2 ARIXTRA was first authorised for use in the EU in March 2002 for the prevention of VTE in patients undergoing major orthopaedic surgery of the lower limbs. ARIXTRA is currently marketed in 30 countries, including major European markets and the United States.2
Safety Information (Clinicians should consult the summary of product characteristics before prescribing)
For both prophylaxis and treatment:
Contraindications
ARIXTRA is contraindicated in patients with severe renal impairment, patients with active major bleeding, bacterial endocarditis, and patients with hypersensitivity to fondaparinux sodium.2 In the United States, ARIXTRA is also contraindicated in patients weighing less than 50kg who are undergoing major surgery of the lower limbs or abdominal surgery.2
Warnings
ARIXTRA is not intended for intramuscular administration.2
ARIXTRA should be used with caution in all patient groups with increased risk of bleeding.2 This includes the elderly, patients with moderate renal or severe hepatic impairment and those weighing less than 50kg.2 ARIXTRA should not be co-administered with drugs that may increase the risk of bleeding.2
When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated with low-molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal haematoma, which can result in long-term or permanent paralysis.2 The risk of these events may be higher with postoperative use of indwelling epidural catheters or concomitant use of drugs affecting haemostasis.2 Spinal/epidural anesthesia should not be used concurrently with ARIXTRA for the treatment of VTE.2
The efficacy and safety of ARIXTRA in patients with heparin induced thrombocytopenia type II has not been studied.2
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References:
1. Agnelli, G., Bergqvist, D., Cohen, A., Gallus, A., et al. (2003). A Randomized Double-Blind Study to Compare the Efficacy and Safety of Postoperative Fondaparinux (Arixtra ) and Preoperative Dalteparin in the Prevention of Venous Thromboembolism after High-Risk Abdominal Surgery: The PEGASUS Study. Session Type: Oral Session. Blood 102(11 Pt 1): 15a.
2. Data on file, GlaxoSmithKline, King of Prussia. gsk.com/media/pressreleases.htm