fondaparinux (Rx)

>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

Spinal or epidural hematomas

Hemorrhage

Increase in bleeding risk with renal impairment

Increase in bleeding risk with body weight <50 Kg

Increase in aminotransferase levels

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); may cause prolonged anticoagulation in patients with CrCl 30 to 50 mL/min

Discontinue if platelets <100,000/μL

Not for IM administration

Therapy increases risk of hemorrhage in patients at risk for bleeding, including conditions 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; cases of elevated aPTT temporally associated with bleeding events have been reported following administration of drug (with or without concomitant administration of other anticoagulants); do not administer agents that enhance risk of hemorrhage unless essential for management of underlying condition, such as vitamin K antagonists for treatment of VTE; if co-administration is essential, closely monitor patients for signs and symptoms of bleeding

Do not use interchangeably with heparin or LMWHs

Thrombocytopenia with thrombosis reported with use; discontinue therapy if platelet count falls below 100,000/mm³

Risk of spinal or epidural hematomas if spinal puncture occurs (see Black Box Warnings)

Do not administer initial dose earlier than 6- 8 hours after surgery; administration earlier than 6 hours after surgery increases risk of major bleeding

Increased risk of bleeding in patients <50 kg; dosage reduction recommended

Not for administration as prophylactic for patients undergoing hip fracture, hip replacement, or knee replacement surgery and abdominal surgery

Pregnancy

Available data from published literature and postmarketing reports have not reported clear association with adverse developmental outcomes; fondaparinux sodium plasma concentrations obtained from four women treated during pregnancy and their newborn infants demonstrated low placental transfer of fondaparinux sodium; there are risks to mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants

Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions; published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy

Fetal/neonatal adverse reactions

• Drug has been demonstrated to cross placenta in humans; use of anticoagulants, may increase risk of bleeding in the fetus and neonate; monitor neonates for bleeding

Labor or delivery

• All patients receiving anticoagulants, including pregnant women, are at risk for bleeding; use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas; pregnant women receiving therapy should be carefully monitored for evidence of bleeding or unexpected changes in coagulation parameters; consideration for use of a shorter acting anticoagulant should be specifically addressed as delivery approaches

Lactation

There are no data on presence in human milk, or effects on milk production; limited clinical data during lactation preclude a clear determination of risk of therapy to an infant during lactation; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

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.

Mechanism of Action

Antithrombotic agent; inhibits factor Xa, which interrupts blood coagulation cascade and inhibits thrombin formation 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