Dosing and uses of Arixtra (fondaparinux)
Adult dosage forms and strengths
prefilled syringe
- 2.5mg/0.5mL
- 5mg/0.4mL
- 7.5mg/0.6mL
- 10mg/0.8mL
Deep Vein Thrombosis/Acute Pulmonary Embolism
Treatment
<50 kg: 5 mg SC once daily
50-100 kg: 7.5 mg SC once daily
>100 kg: 10 mg SC once daily
Administer for 5-9 days; up to 26 days administered in clinical trials
Prophylaxis
>50 kg: 2.5 mg SC once daily for 5-9 days or up to 10 days following abdomonal surgery; for hip replacement, 11 days recommended and a minimum 10-14 days recommended for patients undergoing total hip or knee arthroplasty, or hip fracture surgery; administered for up to 35 days in some instances
Heparin-Induced Thrombocytopenia (Off-label)
Prophylaxis of deep vein thrombosis (DVT) in patient with history of heparin-induced thrombocytopenia (HIT) until patient can switch to warfarin
2.5 mg SC once daily
American College of Chest Physicians (ACCP) guidelines assign low evidence rating to treatment of HIT with fondaparinux and conclude that further studies evaluating its role in HIT treatment are needed
Administration
Administer initial dose 6-8 hours after surgery, once hemostasis has been established
SC administration is deep, alternating right and left anterior and posterior abdominal walls
Pediatric dosage forms and strengths
Safety and efficacy not established
Because bleeding is increased in adults <50 kg, bleeding may be a particular safety concern in children
Arixtra (fondaparinux) adverse (side) effects
>10%
Anemia (1-20%)
Fever (4-14%)
Nausea (3-11%)
1-10%
Rash (7.5%)
Dizziness (4%)
Confusion (3%)
Constipation (5-9%)
Diarrhea (2-3%)
Edema (9%)
Headache (2-5%)
Hypokalemia (1-4%)
Hypotension (4%)
Insomnia (4-5%)
Purpura (4%)
Thrombocytopenia (3%)
Urinary retention (3%)
Urinary tract infection (2-4%)
Vomiting (1-6%)
Postmarketing Reports
Thrombocytopenia with thrombosis that manifested similarly to HIt
Serious allergic reactions, including angioedema and anaphylactoid or anaphylactic reactions
Warnings
Black box warnings
Epidural or spinal hematomas may occur in patients undergoing anticoagulation with low-molecular-weight heparins (LMWHs) or heparinoids who receive neuraxial (epidural or spinal) anesthesia or spinal puncture
These hematomas may result in long-term or permanent paralysis
Patients should be frequently monitored for signs and symptoms of neurologic impairment
If neurologic compromise is noted, urgent treatment is necessary
Physicians should weigh benefits against risk before embarking on neuraxial intervention in patients anticoagulated or scheduled to be anticoagulated for thromboprophylaxis
Optimal timing between the administration of LMWHs and neuraxial procedures is not known
Factors increasing risk of epidural or spinal hematomas
- Indwelling epidural catheters
- Concomitant use of other drugs that affect hemostasis (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], platelet inhibitors, other anticoagulants)
- History of traumatic or repeated epidural or spinal punctures
- History of spinal deformity or spinal surgery
Contraindications
Severe renal impairment (CrCl <30 mL/min)
Body weight <50 kg (venous thromboembolism prophylaxis only)
Active major bleeding
Bacterial endocarditis
Thrombocytopenia with antiplatelet antibody in presence of fondaparinux
History of serious hypersensitivity reaction (eg, angioedema, anaphylactoid or anaphylactic reactions)
Cautions
Use with caution in the elderly (prolonged half-life in patients >75 years of age), peptic ulcer disease, bleeding disorder, recent stroke, recent surgery (brain, spinal cord, or eye), concurrent use of platelet inhibitors or anticoagulants, moderate renal impairment (CrCl 30-50 mL/min)
Discontinue if platelets <100,000/μL
Do not administer Im
Do not use interchangeably with heparin or LMWHs
Thrombocytopenia with thrombosis reported with use
Risk of spinal or epidural hematomas if spinal puncture occurs (see Black box warnings)
Increased risk of bleeding in patients <50 kg; dosage reduction recommended
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether drug is excreted in milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Arixtra (fondaparinux)
Mechanism of action
Antithrombotic agent; inhibits factor Xa, which interrupts blood coagulation cascade and inhibits thrombin formaiton and thrombus development; generally does not increase prothrombin time (PT) or partial thromboplastin time (PTT)
Absorption
Bioavailability: 100%
Peak plasma time: 2-3 hr
Peak plasma concentration: 0.34-0.50 mg/L
Distribution
Protein bound: 94% (antithrombin III)
Vd: 7-11 L
Metabolism
Not established
Elimination
Half-life: 17-21 hr
Dialyzable: Yes
Excretion: Urine
