FDA Approves Fondaparinux sodium for Prevention of Venous Thromboembolism in Abdominal Surgery
May 27, 2005, 19:00, Reviewed by: Dr.
|"This approval provides these high risk patients, particularly cancer surgery patients, the benefit of VTE protection in a once-a-day anticoagulant."
The anti-thrombotic drug ARIXTRA(R) is now indicated for use in patients undergoing abdominal surgery, GlaxoSmithKline (NYSE: GSK) announced today. The U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for ARIXTRA in the prevention of venous thromboembolism (VTE) in patients undergoing abdominal surgery who are at risk of thromboembolic complications.
"Since many patients undergoing abdominal surgery are at high risk of developing VTE, the FDA's approval of ARIXTRA for this new indication represents an important and exciting medical development," said Kevin Lokay, vice president of GlaxoSmithKline Oncology and Acute Care. "This approval provides these high risk patients, particularly cancer surgery patients, the benefit of VTE protection in a once-a-day anticoagulant."
ARIXTRA is the first selective inhibitor of Factor Xa, a protein central to the coagulation process. ARIXTRA is already approved for the prevention 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.
Additionally, ARIXTRA is indicated for the treatment of acute DVT when administered in conjunction with warfarin sodium and for the treatment of acute PE when administered in conjunction with warfarin sodium, when initial therapy is administered in the hospital.
"In addition to demonstrating safety profiles comparable to enoxaparin, dalteparin, and unfractioned heparin, ARIXTRA has not had any reported cases of heparin induced thrombocytopenia (a potentially fatal condition in which
antibodies develop and lead to increased risk of thrombosis) or drug-drug interactions," said Lokay.
VTE is a term that refers to either one or both of two medical conditions: deep vein thrombosis (DVT, which includes blood clots in the pelvic or leg veins), and pulmonary embolism (PE, which is when a clot breaks off and lodges in the lung arteries).
Up to two million cases of VTE develop in the United
States each year.About one-third of patients with symptomatic VTE will develop PE. VTE can be fatal; death occurs in about six percent of DVT cases and about 12 percent of PE cases within one month of diagnosis. Without prophylaxis, up to 25 percent of patients undergoing abdominal surgery will develop DVT, with a 0.5 to 0.8
percent associated risk of PE. In patients undergoing cancer surgery, the risk of VTE and fatal PE is two to four times higher.
The recent approval of ARIXTRA for patients undergoing abdominal surgery is based on the results of the PEntasaccharide GenerAl SUrgery Study (PEGASUS). This non-inferiority study demonstrated that ARIXTRA is at least
as effective as dalteparin in reducing the risk of VTE. In the study, 4.6 percent of patients receiving ARIXTRA experienced a VTE incident versus 6.1 percent of patients on dalteparin. Sixty-nine percent of the patients in the
study underwent cancer-related abdominal surgery with 4.7 percent of patients in the ARIXTRA group experiencing VTE versus 7.7 percent of patients in the dalteparin group. In non-cancer abdominal surgery patients studied, 4.2 percent of patients receiving ARIXTRA experienced VTE versus 2.3 percent of patients receiving dalteparin.
PEGASUS was a double-blind, non-inferiority study performed in 131 centers in 22 countries. A total of 2927 patients were randomized to receive either subcutaneous ARIXTRA 2.5 mg once daily starting six hours after surgery or subcutaneous dalteparin (2500 IU two hours before surgery; 2500 IU on the evening following surgery; then 5000 IU once daily). Treatment was continued for 7 +/- 2 days and patients were followed-up for 30 +/- 2 days. The main sites of surgery were colonic/rectal, gastric, hepatic, cholecystectomy orother biliary.
The primary efficacy endpoint was the incidence of VTE, including DVT and/or PE, evaluated up to post-surgical Day 10 (4.6 percent for ARIXTRA and 6.1 percent for dalteparin). The primary safety outcome was major bleeding
during the initial treatment period, which was comparable between the two groups (3.4 percent for ARIXTRA versus 2.4 percent for dalteparin). However, in patients treated with ARIXTRA according to the recommended regimen (e.g.,
first dose initiated 6 to 8 hours after surgery), the rate of major bleeding was 2.9 percent.
ARIXTRA Safety Information
For Both Prophylaxis and Treatment:
When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low-molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The risk of these events may be higher with postoperative use of indwelling epidural catheters or concomitant use of drugs affecting
hemostasis. Patients should be frequently monitored for signs and symptoms of neurological impairment. (See BOXED WARNING)
ARIXTRA is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), patients undergoing hip fracture, hip replacement or knee replacement surgery and abdominal surgery with body weight
less than 50 kg ( less than 110 lbs), patients with active major bleeding, bacterial endocarditis, patients with thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium, or patients with hypersensitivity to fondaparinux sodium.
ARIXTRA is not intended for intramuscular administration.
ARIXTRA cannot be used interchangeably with heparin, low-molecular-weight heparins or heparinoids as they differ in manufacturing process, anti-Xa and anti-IIa activity, units, and dosage.
The risk of hemorrhage increases with increasing renal impairment.ARIXTRA should be used with caution in patients with moderate renal impairment. Renal function should be assessed periodically in patients receiving ARIXTRA and should be discontinued immediately in patients who develop severe renal impairment ARIXTRA, like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage.
Thrombocytopenia can occur with ARIXTRA. If the platelet count falls below 100,000/mm3, ARIXTRA should be discontinued.
- U.S. Food and Drug Administration (FDA)
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Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2004.
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