Fondaparinux warnings and precautions

Fondaparinux
Arixtra® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages
Clinical Trials on Fondaparinux
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

Warnings And Precautions

Hemorrhage

Use ARIXTRA 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, uncontrolled arterial hypertension, diabetic retinopathy, or shortly after brain, spinal, or ophthalmological surgery. Isolated cases of elevated aPTT temporally associated with bleeding events have been reported following administration of ARIXTRA (with or without concomitant administration of other anticoagulants) [see Adverse Reactions (6.5)].

Do not administer agents that enhance the risk of hemorrhage with ARIXTRA unless essential for the management of the underlying condition, such as vitamin K antagonists for the treatment of VTE. If co-administration is essential, closely monitor patients for signs and symptoms of bleeding.

Do not administer the initial dose of ARIXTRA earlier than 6 to 8 hours after surgery. Administration earlier than 6 hours after surgery increases risk of major bleeding [see Dosage and Administration (2) and Adverse Reactions (6.1)].

Renal Impairment and Bleeding Risk

ARIXTRA increases the risk of bleeding in patients with impaired renal function due to reduced clearance [see Clinical Pharmacology (12.4)].

The incidence of major bleeding by renal function status reported in clinical trials of patients receiving ARIXTRA for VTE surgical prophylaxis is provided in Table 1. In these patient populations, the following is recommended:

• Do not use ARIXTRA for VTE prophylaxis and treatment in patients with CrCl <30 mL/min [see Contraindications (4)].
• Use ARIXTRA with caution in patients with CrCl 30 to 50 mL/min.

Assess renal function periodically in patients receiving ARIXTRA. Discontinue the drug immediately in patients who develop severe renal impairment while on therapy. After discontinuation of ARIXTRA, its anticoagulant effects may persist for 2 to 4 days in patients with normal renal function (i.e., at least 3 to 5 half-lives). The anticoagulant effects of ARIXTRA may persist even longer in patients with renal impairment [see Clinical Pharmacology (12.4)].

Bleeding Risk When Body Weight < 50 Kg

ARIXTRA increases the risk for bleeding in patients who weigh less than 50 kg, compared to patients with higher weights.

In patients who weigh less than 50 kg:

• Do not administer ARIXTRA as prophylactic therapy for patients undergoing hip fracture, hip replacement, or knee replacement surgery and abdominal surgery [see Contraindications (4)].
• Use ARIXTRA with caution in the treatment of PE and DVT.

During the randomized clinical trials of VTE prophylaxis in the peri-operative period following hip fracture, hip replacement, or knee replacement surgery and abdominal surgery, major bleeding occurred at a higher rate among patients with a body weight <50 kg compared to those with a body weight >50 kg (5.4% versus 2.1% in patients undergoing hip fracture, hip replacement, or knee replacement surgery; 5.3% versus 3.3% in patients undergoing abdominal surgery).

Thrombocytopenia

Thrombocytopenia can occur with the administration of ARIXTRA. Thrombocytopenia of any degree should be monitored closely. Discontinue ARIXTRA if the platelet count falls below 100,000/mm3. 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.

Isolated occurrences of thrombocytopenia with thrombosis that manifested similar to heparin-induced thrombocytopenia have been reported with the use of ARIXTRA in postmarketing experience. [See Adverse Reactions (6.5).]

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]. In the postmarketing experience, epidural or spinal hematoma has been reported in association with the use of ARIXTRA by subcutaneous (SC) injection. Monitor patients undergoing these procedures for signs and symptoms of neurologic impairment. Consider the potential risks and benefits before neuraxial intervention in patients anticoagulated or who may be anticoagulated for thromboprophylaxis.

Monitoring: Laboratory Tests

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 unexpected changes in coagulation parameters or major bleeding occur during therapy with ARIXTRA, discontinue ARIXTRA. In postmarketing experience, isolated occurrences of aPTT elevations have been reported following administration of ARIXTRA [see Adverse Reactions (6.5)].

Periodic routine complete blood counts (including platelet count), serum creatinine level, and stool occult blood tests are recommended during the course of treatment with ARIXTRA.

The anti-Factor Xa activity of fondaparinux sodium can be measured by anti-Xa assay using the appropriate calibrator (fondaparinux). The activity of fondaparinux sodium is expressed in milligrams (mg) of the fondaparinux and cannot be compared with activities of heparin or low molecular weight heparins. [See Clinical Pharmacology (12.2, 12.3).]

Latex

The packaging (needle guard) of the prefilled syringe of ARIXTRA contains dry natural latex rubber that may cause allergic reactions in latex sensitive individuals.

References

Adapted from the FDA Package Insert.