Fondaparinux warnings

Warnings
Arixtra Injection is not intended for intramuscular administration.

Arixtra cannot be used interchangeably (unit for unit) with heparin, low molecular weight heparins or heparinoids, as they differ in manufacturing process, anti-Xa and anti-IIa activity, units, and dosage. Each of these medicines has its own instructions for use.

Renal Impairment

 * Hip Fracture, Hip Replacement and Knee Replacement Surgeries

Major bleeding in patients receiving prophylactic therapy in hip fracture, hip replacement, or knee replacement surgery occurred in 1.6% (25/1,565) of patients with normal renal function, in 2.4% (31/1,288) with mild renal impairment, in 3.8% (19/504) with moderate renal impairment, and in 4.8% (4/83) with severe renal impairment. When Arixtra was used according to the recommended timing of the first injection (6 to 8 hours after surgery), major bleeding occurred in 1.8% (16/905) of patients with normal renal function, in 2.2% (15/675)with mild renal impairment, in 2.3% (6/265) with moderate renal impairment, and in 0% (0/40) with severe renal impairment.


 * Abdominal Surgery

Major bleeding in patients receiving prophylactic therapy in abdominal surgery occurred in 2.1% (13/606) of patients with normal renal function, in 3.6% (22/613) with mild renal impairment, in 6.7% (12/179) with moderate renal impairment, and in 7.1% (1/14) with severe renal impairment. When Arixtra was used according to the recommended timing of the first injection (6 to 8 hours after surgery), major bleeding occurred in 2.1% (10/467) of patients with normal renal function, in 3.3% (16/481) with mild renal impairment, in 5.8% (8/137) with moderate renal impairment, and in 7.7% (1/13) with severe renal impairment.


 * Treatment of Deep Vein Thrombosis and Pulmonary Embolism

Major bleeding in patients receiving treatment for DVT and PE occurred in 0.4% (4/1,132) of patients with normal renal function, in 1.6% (12/733) with mild renal impairment, in 2.2% (7/318) with moderate renal impairment, and in 7.3% (4/55) with severe renal impairment.

Arixtra should be used with caution in patients with moderate renal impairment (creatinine clearance 30-50 mL/min).

Renal function should be assessed periodically in patients receiving Arixtra. The drug should be discontinued immediately in patients who develop severe renal impairment while on therapy. After discontinuation of Arixtra, its anticoagulant effects may persist for 2-4 days in patients with normal renal function (i.e., at least 3-5 half-lives). The anticoagulant effects of Arixtra may persist even longer in patients with renal impairment.

Hemorrhage
Arixtra Injection, like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage, such as congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors.

Laboratory Testing
Because routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive measures of the activity of Arixtra and international standards of heparin or LMWH are not calibrators to measure anti-Factor Xa activity of Arixtra, if during therapy with Arixtra, unexpected changes in coagulation parameters or major bleeding occurs, Arixtra should be discontinued.

Neuraxial Anesthesia and Post-operative Indwelling Epidural Catheter Use
Spinal or epidural hematomas, which may result in long-term or permanent paralysis, can occur with the use of anticoagulants and neuraxial (spinal/epidural) anesthesia or spinal puncture. The risk of these events may be higher with post-operative use of indwelling epidural catheters or concomitant use of other drugs affecting hemostasis such as NSAIDs (see Boxed Warning for Spinal/Epidural Hematomas). In spontaneous post-marketing reports, there have been several cases of epidural or spinal hematoma that have occurred in association with the use of Arixtra by SC injection.

Thrombocytopenia
Thrombocytopenia can occur with the administration of Arixtra. Moderate thrombocytopenia (platelet counts between 100,000/mm3 and 50,000/mm3) occurred at a rate of 3.0% in patients given Arixtra 2.5 mg in the peri-operative hip fracture, hip replacement or knee replacement surgery, and abdominal surgery clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm3) occurred at a rate of 0.2% in patients given Arixtra 2.5 mg in these clinical trials. During extended prophylaxis, no cases of moderate or severe thrombocytopenia were reported.

Moderate thrombocytopenia occurred at a rate of 0.5% in patients given the Arixtra treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given the Arixtra treatment regimen in the DVT and PE treatment clinical trials.

Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3, Arixtra should be discontinued.