Fondaparinux side effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying possible adverse events and for approximating rates.

The data described below reflect exposure in 8,877 patients randomized to Arixtra Injection in controlled trials of hip fracture, hip replacement, major knee, or abdominal surgeries, and DVT and PE treatment. Patients received Arixtra primarily in 2 large peri-operative dose-response trials (n = 989), 4 active-controlled peri-operative trials with enoxaparin sodium (n = 3,616), and an extended prophylaxis trial (n = 327), an active-controlled trial with dalteparin sodium (n = 1,425), a dose-response trial in DVT treatment (n = 111), an active-controlled trial with enoxaparin sodium in DVT treatment (n = 1,091), and an active-controlled trial with heparin in PE treatment (n = 1,092).

Hemorrhage
During administration of Arixtra, the most common adverse reactions were bleeding complications.

Thrombocytopenia
See WARNINGS: Thrombocytopenia

Local Reactions
Mild local irritation (injection site bleeding, rash, and pruritus) may occur following subcutaneous injection of Arixtra.

Elevations of Serum Aminotransferases
In the peri-operative prophylaxis randomized clinical trials of 7 ± 2 days asymptomatic increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in 1.7% and 2.6% of patients, respectively, during treatment with Arixtra 2.5 mg Injection versus 3.2% and 3.9%, of patients, respectively, during treatment with enoxaparin sodium 30 mg every 12 hours or 40 mg once daily enoxaparin sodium. Such elevations are fully reversible and are rarely associated with increases in bilirubin. In the extended prophylaxis clinical trial no significant differences in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels between Arixtra 2.5 mg Injection and placebo treated patients were observed.

In the DVT and PE treatment clinical trials asymptomatic increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in 0.7% and 1.3% of patients, respectively, during treatment with the Arixtra injection treatment regimen. In comparison, these increases have been reported in 4.8% and 12.3%, of patients, respectively, in the DVT treatment trial during treatment with enoxaparin sodium 1 mg/kg every 12 hours, and in 2.9% and 8.7%, of patients, respectively, in the PE treatment trial during treatment with aPTT adjusted heparin.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like Arixtra should be interpreted with caution.

Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Arixtra. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Rare cases of elevated aPTT and heparin-induced thrombocytopenia have been reported. A causal relationship of these events to fondaparinux has not been established.

Hematologic side effects
Hematologic side effects associated with the administration of fondaparinux have included major bleeding, anemia, purpura, thrombocytopenia, postoperative hemorrhage and hematoma. Occurrences of major bleeding in patients receiving therapeutic regimen in treatment of DVT and PE with normal renal function, mild renal impairment, moderate renal impairment, and severe renal impairment have been found to be 0.4%, 1.6%, 2.2%, and 7.3%, respectively. Moderate thrombocytopenia occurred at a rate of 0.5% in patients given fondaparinux treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given fondaparinux treatment regimen in the DVT and PE treatment clinical trials.

Rare cases of elevated aPTT and heparin-induced thrombocytopenia have been reported. A causal relationship of these events to fondaparinux has not been established.

Hepatic side effects
Hepatic side effects associated with the administration of fondaparinux have included elevated aminotransferase levels.

Local side effects
Local side effects associated with the administration of fondaparinux have included injection site bleeding, rash, and pruritus.

Gastrointestinal side effects
Gastrointestinal side effects associated with the administration of fondaparinux have included nausea, vomiting, constipation, diarrhea, and dyspepsia.

Nervous system side effects
Nervous system side effects associated with the administration of fondaparinux have included insomnia, dizziness, and confusion.

Dermatologic side effects
Dermatologic side effects associated with the administration of fondaparinux have included rash, increased wound drainage, and bullous eruption.

Cardiovascular side effects
Cardiovascular side effects associated with the administration of fondaparinux have included hypotension and edema.

Genitourinary side effects
Genitourinary side effects associated with the administration of fondaparinux have included urinary tract infection and urinary retention.

Metabolic side effects
Metabolic side effects associated with the administration of fondaparinux have included hypokalemia.

Other side effects
Other side effects associated with the administration of fondaparinux have included fever, headache, and pain.