Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies in animals have been performed to evaluate the carcinogenic potential of fondaparinux sodium.
Fondaparinux sodium was not genotoxic in the Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, the human lymphocyte chromosome aberration test, the rat hepatocyte unscheduled DNA synthesis (UDS) test, or the rat micronucleus test.
At subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human dose based on body surface area), fondaparinux sodium was found to have no effect on fertility and reproductive performance of male and female rats.
Pregnancy Category B. Reproduction studies have been performed in pregnant rats at subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human dose based on body surface area) and pregnant rabbits at subcutaneous doses up to 10 mg/kg/day (about 65 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to fondaparinux sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
ARIXTRA Injection is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). ARIXTRA is eliminated primarily by the kidneys, and such patients are at increased risk for major bleeding episodes (see WARNINGS: Renal Impairment).
ARIXTRA prophylactic therapy is contraindicated in patients with body weight <50 kg undergoing hip fracture, hip replacement or knee replacement surgery, and abdominal surgery. During the randomized clinical trials of prophylaxis in the peri-operative period following hip fracture, hip replacement, or knee replacement surgery, occurrence of major bleeding was doubled in patients with a body weight <50 kg compared with those with a body weight ≥50 kg (5.4% versus 2.1%). In the clinical trial in patients undergoing abdominal surgery, the major bleeding rate was also higher in patients with a body weight <50 kg as compared to those with a body weight ≥50 kg (5.3% versus 3.3%), respectively.
The use of ARIXTRA is contraindicated in patients with active major bleeding, bacterial endocarditis, in patients with thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium, or in patients with known hypersensitivity to fondaparinux sodium.