Fondaparinux Sodium Prescribing Information
- use of indwelling epidural catheters
- concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants
- a history of traumatic or repeated epidural or spinal puncture
- a history of spinal deformity or spinal surgery
- Optimal timing between the administration of fondaparinux sodium and neuraxial procedures is not known.
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
In clinical studies performed with fondaparinux sodium, the concomitant use of oral anticoagulants (warfarin sodium), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, fondaparinux sodium neither influenced the pharmacodynamics of warfarin sodium, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state.
Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of therapy with fondaparinux sodium unless these agents are essential. If co-administration is necessary, monitor patients closely for hemorrhage
In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 micromolar i.e., 350 mg/L) was 17% to 28%. Inhibition of the other isozymes evaluated (CYPs 1A2, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0% to 16%. Since fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro, fondaparinux sodium is not expected to significantly interact with other drugs in vivo by inhibition of metabolism mediated by these isozymes.
Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no drug interactions by protein-binding displacement are expected.
Discontinue agents that may enhance the risk of hemorrhage prior to initiation of therapy with fondaparinux sodium unless essential. If co-administration is necessary, monitor patients closely for hemorrhage. (7)
Do not mix other medications or solutions with fondaparinux sodium injection. Administer fondaparinux sodium injection only subcutaneously. Discard unused portion.
Monitor routine complete blood counts (including platelet count), serum creatinine level, and stool occult blood periodically
Injection: Single-dose, prefilled syringes containing clear and colorless to slightly yellow liquid containing either 2.5 mg/0.5 mL, 5 mg/0.4 mL, 7.5 mg/0.6 mL, or 10 mg/0.8 mL of fondaparinux sodium.
Fondaparinux sodium injection is contraindicated in the following conditions:
• Severe renal impairment (creatinine clearance [CrCl] less than 30 mL/min)
• Active major bleeding.
• Bacterial endocarditis.
• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.
• Body weight less than 50 kg (venous thromboembolism [VTE] prophylaxis in adults only)
• History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to fondaparinux sodium.
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Spinal or epidural hematomas
• Hemorrhage
• Renal impairment and bleeding risk
• Body weight less than 50 kg and bleeding risk
• Thrombocytopenia
In clinical studies performed with fondaparinux sodium, the concomitant use of oral anticoagulants (warfarin sodium), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, fondaparinux sodium neither influenced the pharmacodynamics of warfarin sodium, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state.
Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of therapy with fondaparinux sodium unless these agents are essential. If co-administration is necessary, monitor patients closely for hemorrhage
In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 micromolar i.e., 350 mg/L) was 17% to 28%. Inhibition of the other isozymes evaluated (CYPs 1A2, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0% to 16%. Since fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro, fondaparinux sodium is not expected to significantly interact with other drugs in vivo by inhibition of metabolism mediated by these isozymes.
Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no drug interactions by protein-binding displacement are expected.