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Fondaparinux

Class: Anticoagulants, Miscellaneous
Chemical Name: MethylO-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-d-glucopyranosyl-(1→4)-O-β-d-glucopyranuronosyl-(1→4)-O-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-d-glucopyranosyl-(1→4)-O-2-O-sulfo-α-l-idopyranuronosyl-(1→4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-d-glucopyranoside decasodium salt
Molecular Formula: C31H43N3Na10O49S8
CAS Number: 114870-03-0
Brands: Arixtra

Medically reviewed by Drugs.com on Nov 29, 2021. Written by ASHP.

Warning

    Spinal/Epidural Hematoma Risk
  • Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight heparins (LMWHs), heparinoids, or fondaparinux and neuraxial (spinal/epidural) anesthesia or spinal puncture.

  • Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet-aggregation inhibitors, other anticoagulants).

  • Risk also increased by history of traumatic or repeated epidural or spinal puncture, spinal deformity, or spinal surgery.

  • Optimal timing between administration of fondaparinux and neuraxial procedures not known.

  • Monitor frequently for manifestations of neurologic impairment and treat urgently if neurologic compromise noted.

  • Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants. (See Spinal/Epidural Hematoma under Cautions and also see Interactions.)

Introduction

Anticoagulant; a synthetic activated factor Xa inhibitor.

Uses for Fondaparinux

Thromboprophylaxis in Major Orthopedic Surgery

Prevention of postoperative DVT and PE in patients undergoing hip-fracture, hip-replacement, or knee-replacement surgery.

Used for extended prophylaxis (for up to 35 days postoperatively) in patients undergoing hip-fracture surgery.

The American College of Chest Physicians (ACCP) recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism (VTE); continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.

Fondaparinux is recommended by ACCP as one of several anticoagulant options for VTE prophylaxis in patients undergoing major orthopedic surgery.

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, bleeding risk, logistics, and compliance issues.

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing abdominal surgery and other nonorthopedic general surgery settings who are at risk for thromboembolic complications.

ACCP recommends pharmacologic and/or nonpharmacologic (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general (nonorthopedic) surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.

If pharmacologic prophylaxis is indicated, ACCP states that LMWHs or low-dose unfractionated heparin is preferred; fondaparinux may be considered when these agents are contraindicated or not available.

Cancer is an additional risk factor for VTE. Current therapeutic guidelines such as those from the American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) recommend fondaparinux as an option for VTE prophylaxis in surgical patients with cancer.

Medical Conditions Associated with Thromboembolism

Also used for VTE prophylaxis in acutely ill, hospitalized medical patients (including cancer patients) at increased risk of thrombosis; ACCP recommends fondaparinux as an option for thromboprophylaxis in such patients.

Treatment decisions regarding thromboprophylaxis in acutely ill hospitalized patients should include an assessment of the patient's individual risk of VTE and risk of bleeding.

Cancer is a risk factor for VTE in hospitalized medical patents. Fondaparinux may be used in cancer patients requiring thromboprophylaxis in the inpatient setting.

Treatment of DVT and PE

Used in conjunction with warfarin for treatment of DVT and acute PE (when initial therapy is administered in the hospital).

Recommended by ACCP as one of several parenteral anticoagulant options for initial treatment of VTE; however, initial treatment with a parenteral anticoagulant may not always be necessary since oral anticoagulant options are available.

For patients treated with initial parenteral anticoagulation, ACCP recommends LMWHs or fondaparinux over unfractionated heparin.

In patients with cancer and established VTE, LMWHs or direct oral anticoagulants (DOACs) generally recommended. Fondaparinux may be used for initial anticoagulation; however, generally not recommended for long-term use because of a higher rate of recurrent thrombosis.

Treatment of Superficial Vein Thrombosis

Has been used for treatment of superficial vein thrombosis (or thrombophlebitis); prophylaxis for 45 days suggested in patients with superficial vein thrombosis ≥5 cm in length.

Acute Coronary Syndrome

Has been used in patients with acute coronary syndrome (ACS), including those with ST-segment-elevation myocardial infarction (STEMI) undergoing thrombolysis or revascularization procedures (e.g., PCI) and those with non-ST-segment-elevation ACS (NSTE-ACS) being managed with conservative therapies or revascularization strategies (e.g., PCI, CABG).

The American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) state that in patients with STEMI undergoing thrombolytic therapy, an anticoagulant (e.g., unfractionated heparin, enoxaparin, fondaparinux) should be administered for ≥48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization is performed.

Initial parenteral anticoagulants with established efficacy in patients with NSTE-ACS include enoxaparin, unfractionated heparin, bivalirudin (only in patients managed with an early invasive strategy), and fondaparinux.

If PCI is performed while a patient is receiving fondaparinux, administer an additional anticoagulant with anti-factor IIa (antithrombin) activity because of the risk of catheter thrombosis.

Heparin-induced Thrombocytopenia

Has been used for treatment of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). Although limited data suggest possible effectiveness, ACCP recommends other nonheparin anticoagulants such as lepirudin or argatroban because of more extensive data.

Fondaparinux also has been used as a nonheparin anticoagulant alternative in patients with acute VTE (not related to HIT) who have a history of HIT; however, evidence to support this use is limited.

Fondaparinux Dosage and Administration

General

    Pretreatment Screening
  • Evaluate the possibility of an underlying bleeding disorder before initiating treatment.

    Patient Monitoring
  • Routine monitoring of coagulation parameters not required.

Administration

Administer by sub-Q injection; do not give IM.

Has been administered by direct IV injection initially in the treatment of acute STEMI.

Patients should be sitting or supine during administration.

Increased risk of major bleeding if administered <6 hours after surgery.

Sub-Q Administration

Administer by sub-Q injection, alternating injection sites daily (e.g., between the left and right anterolateral or posterolateral abdominal wall).

Dosage

The activity of fondaparinux sodium is measured based on plasma drug concentrations quantified by anti-factor Xa activity using fondaparinux as the calibrator.

Dosage of fondaparinux sodium is expressed in terms of the salt.

Adults

VTE Prophylaxis
Hip-Fracture, Hip-Replacement, or Knee-Replacement Surgery
Sub-Q

Patients weighing ≥50 kg: 2.5 mg once daily. Manufacturer recommends that initial dose be given no earlier than 6–8 hours after surgery, provided hemostasis has been established. Avoid use in patients weighing <50 kg. (See Contraindications under Cautions.)

Usual duration of therapy is 5–9 days, although up to 11 days has been studied in clinical trials of orthopedic surgery.

Extended prophylaxis: Extended thromboprophylaxis for up to 35 days is recommended in patients undergoing hip-fracture surgery, and suggested for patients undergoing other major orthopedic procedures.

Abdominal Surgery
Sub-Q

Patients weighing ≥50 kg: 2.5 mg once daily, with the initial dose given 6–8 hours after surgery, provided hemostasis has been established. Avoid use in patients weighing <50 kg. (See Contraindications under Cautions.)

Usual duration of therapy is 5–9 days, although up to 10 days has been studied.

VTE Treatment
Sub-Q

Patients weighing <50 kg: 5 mg once daily.

Patients weighing 50–100 kg: 7.5 mg once daily.

Patients weighing >100 kg: 10 mg once daily.

Usual duration of therapy is 5–9 days, although up to 26 days of treatment has been used.

Initiate concurrent warfarin as soon as possible, usually within 72 hours of fondaparinux injection; the American College of Chest Physicians (ACCP) recommends initiating warfarin simultaneously on the first day of fondaparinux treatment.

Continue fondaparinux and warfarin for ≥5 days and until an adequate response to warfarin is achieved (i.e., a stable INR of 2–3); ACCP recommends continuing concomitant therapy for ≥5 days and until INR of 2–3 has been maintained for ≥24 hours.

NSTE ACS†
Sub-Q

2.5 mg sub-Q once daily has been used.

In patients receiving fondaparinux prior to PCI, administer additional treatment with an IV anticoagulant with anti-factor IIa (antithrombin) activity; consider whether glycoprotein (GP) IIb/IIIa-receptor inhibitor therapy has been administered.

STEMI†
IV, then Sub-Q

Has been administered at an initial dose of 2.5 mg by direct IV injection, followed by dosage of 2.5 mg sub-Q once daily for duration of hospitalization or up to 8 days or until revascularization.

In patients receiving fondaparinux prior to PCI, administer additional treatment with an IV anticoagulant with anti-factor IIa (antithrombin) activity; consider whether GP IIb/IIIa-receptor inhibitor therapy has been administered.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment. Pharmacokinetics not evaluated in patients with severe hepatic impairment. (See Hepatic Impairment under Cautions.)

Renal Impairment

Contraindicated in patients with severe renal impairment (Clcr <30 mL/minute); increased risk for major bleeding episodes. Exercise caution in patients with other degrees of renal impairment.

Geriatric Patients

No specific dosage recommendations; however, careful attention to dosage directions recommended.

Cautions for Fondaparinux

Contraindications

  • Patients with severe renal impairment (Clcr <30 mL/minute).

  • Prophylactic use in patients who weigh <50 kg.

  • Active major bleeding, bacterial endocarditis, or thrombocytopenia associated with a positive in vitro test for antiplatelet antibody (HIT) in the presence of the drug.

  • History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to fondaparinux.

Warnings/Precautions

Warnings

Spinal/Epidural Hematoma

Epidural or spinal hematoma reported with concurrent use of anticoagulants (e.g., LMWHs, heparinoids, fondaparinux) and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures. Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis. (See Boxed Warning.)

Optimal timing between administration of fondaparinux and neuraxial procedures not known. Frequently monitor for signs of neurologic impairment (e.g., midline back pain; numbness, tingling, or weakness in lower limbs; bowel or bladder dysfunction). Carefully consider potential benefits versus risks of neuraxial intervention in patients who are currently receiving or will receive anticoagulant prophylaxis; some experts suggest avoidance of fondaparinux prophylaxis in patients receiving epidural analgesia.

Bleeding

Use with extreme caution in patients with an increased risk of hemorrhage (e.g., congenital or acquired bleeding disorders; active ulceration and angiodysplastic GI disease; hemorrhagic stroke; uncontrolled arterial hypertension; diabetic retinopathy; recent brain, spinal, or ophthalmic surgery).

Contraindicated for prophylactic use in patients weighing <50 kg. In such patients, total clearance is reduced by approximately 30%. In patients weighing <50 kg receiving fondaparinux for treatment of VTE, use recommended weight-specific dosage.

Periodic routine blood counts, including platelet counts, and tests for occult blood in stool recommended.

Risk of bleeding is increased in patients with renal impairment. (See Renal Impairment under Cautions.)

Avoid concomitant use of drugs that increase risk of bleeding unless essential (e.g., concomitant use of warfarin for treatment of VTE). Closely monitor for signs and symptoms of bleeding.

Do not administer earlier than 6–8 hours after surgery because of increased risk of major bleeding.

Thrombocytopenia

Moderate thrombocytopenia (platelet counts of 50,000–100,000/mm3) and severe thrombocytopenia (platelet counts <50,000/mm3) reported. Fondaparinux unlikely to cause HIT; however, isolated cases of thrombocytopenia with thrombosis resembling HIT reported during postmarketing experience.

Manufacturer recommends monitoring thrombocytopenia of any degree closely and discontinuing fondaparinux if platelet counts fall below 100,000/mm3.

Patients with Prosthetic Heart Valves

Manufacturer states that fondaparinux has not been studied in patients with prosthetic heart valves and that no information is available on safety of the drug in such patients, although a few case reports typically in the setting of HIT have been published.

Sensitivity Reactions

Latex Sensitivity

Some packaging components (e.g., needle covers) contain natural latex proteins in the form of dry natural rubber (latex), which may cause allergic-type reactions (including life-threatening hypersensitivity reactions) in susceptible individuals. The needle cover of the diluent syringe should not be handled by individuals sensitive to latex.

Specific Populations

Pregnancy

No clear association between fondaparinux use during pregnancy and adverse developmental outcomes.

Placental transfer of fondaparinux observed; however, no adverse effects reported in infants.

Risk of epidural or spinal hematomas in women receiving neuraxial anesthesia during labor and delivery. Consider switching to alternative anticoagulant as delivery date approaches.

Consider risk of untreated thromboembolic disease and risk of bleeding in the mother and fetus when using anticoagulants, including fondaparinux, during pregnancy.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Limited clinical data do not establish clear risk with use during breast-feeding. Not known if the drug has any effects on milk production. The American College of Chest Physicians (ACCP) suggests the use of alternative anticoagulants in nursing women.

Pediatric Use

Safety and efficacy not established in children <17 years of age. Potential for increased bleeding risk in pediatric patients weighing <50 kg.

Geriatric Use

Use with caution. No substantial differences in efficacy relative to younger adults. Possible increased major bleeding or other serious adverse effects in patients ≥75 years of age compared with younger adults. Substantially eliminated by kidneys; assess renal function periodically since geriatric patients are more likely to have decreased renal function. Careful attention to dosage directions and concomitant therapy (particularly platelet-aggregation inhibitors) is advised.

Hepatic Impairment

Following a single 7.5-mg dose in patients with moderate hepatic impairment, response (i.e., aPTT, PT/INR, and antithrombin III) similar to that in patients with normal hepatic function. Pharmacokinetics not studied in patients with severe hepatic impairment.

Increased risk of hemorrhage; closely monitor for signs and symptoms of bleeding.

Renal Impairment

Total clearance is reduced by 25, 40, or 55% in patients with mild, moderate, or severe renal impairment, respectively, compared with those with normal renal function.

In patients with renal impairment, anticoagulant effects may persist for more than 2–4 days following discontinuance of therapy.

Use with caution in patients with moderate renal impairment (Clcr 30–50 mL/minute) due to potential for prolonged anticoagulation and increased risk of hemorrhage. Contraindicated in patients with severe renal impairment (Clcr <30 mL/minute).

Assess renal function periodically (e.g., serum creatinine determinations). Discontinue immediately in patients who develop severe renal impairment during therapy.

In dialysis-dependent patients, approximately 20% of the drug is removed by hemodialysis.

Common Adverse Effects

Bleeding complications.

Interactions for Fondaparinux

Weak inhibitor of CYP2A6, 1A2, 2C9, 2C19, 2D6, 3A4, and 3E1 in vitro.

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.

Protein-bound Drugs

Pharmacokinetic interaction unlikely.

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral (e.g., warfarin)

Increased risk of bleeding

Discontinue oral anticoagulants prior to initiation of fondaparinux

If coadministration is essential, monitor patients closely

Antiplatelet agents (e.g., aspirin)

Increased risk of bleeding

Discontinue antiplatelet agent prior to initiation of fondaparinux

If coadministration is essential, monitor patients closely

Digoxin

Pharmacokinetic/pharmacodynamic interaction unlikely

NSAIAs

Increased risk of bleeding

Discontinue NSAIAs prior to initiation of fondaparinux

If coadministration is essential, monitor patients closely

Fondaparinux Pharmacokinetics

Absorption

Bioavailability

Sub-Q: Absolute bioavailability 100%.

Duration

Anticoagulant effects may persist for 2–4 days following discontinuance of therapy in patients with normal renal function (i.e., ≥3–5 half-lives).

Distribution

Extent

In healthy adults, distributes mainly in blood and only to a minor extent in extravascular fluid. Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

In vitro, 94% bound to antithrombin III.

Elimination

Metabolism

Most of dose not metabolized.

Elimination Route

Eliminated unchanged in urine in individuals with normal renal function.

Half-life

17–21 hours.

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not mix with other injections or infusions.

Actions

  • Anticoagulation results from rapid inhibition of factor Xa by antithrombin III bound to fondaparinux (about 300-fold greater than innate activity). Neutralization of coagulation factor Xa inhibits the conversion of prothrombin to thrombin and subsequent thrombus formation. Unable to lyse established thrombi.

  • Binds selectively to antithrombin III; unable to inactivate thrombin. At the recommended dosage, fibrinolytic activity not affected.

  • Platelet function or global clotting function tests (e.g., PT, bleeding time, aPTT) generally not affected when administered at the recommended dosage.

Advice to Patients

  • Importance of advising patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., back pain; numbness, tingling, or weakness in lower limbs; bowel or bladder dysfunction), particularly if they are receiving concomitant NSAIAs, platelet-aggregation inhibitors, or other anticoagulants; importance of immediately contacting a clinician if any of these symptoms occur.

  • Importance of informing patients that concomitant use of aspirin or other NSAIAs can increase risk of bleeding, and to discontinue use of these drugs whenever possible.

  • If fondaparinux therapy is to be continued after hospital discharge, importance of instructing patient on proper administration of the drug, including injection technique.

  • Importance of informing patients that they may bruise and/or bleed more easily and that a longer than normal time may be required to stop bleeding when taking fondaparinux. Importance of patients reporting any unusual bleeding, bruising, or signs of thrombocytopenia (e.g., dark red spots under skin) to their clinician.

  • Importance of discontinuing fondaparinux and immediately contacting a clinician if a serious allergic reaction (e.g., swelling of the face or mouth, difficulty swallowing or breathing) occurs.

  • Importance of patients informing clinicians (including dentists) that they are receiving fondaparinux therapy before scheduling any invasive procedures.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fondaparinux Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

2.5 mg/0.5 mL*

Arixtra (available as a 0.5-mL, disposable prefilled syringe)

Mylan

Fondaparinux Sodium Injection

5 mg/0.4 mL*

Arixtra (available as a 0.4-mL, disposable prefilled syringe)

Mylan

Fondaparinux Sodium Injection

7.5 mg/0.6 mL*

Arixtra (available as a 0.6-mL, disposable prefilled syringe)

Mylan

Fondaparinux Sodium Injection

10 mg/0.8 mL*

Arixtra (available as a 0.8-mL, disposable prefilled syringe)

Mylan

Fondaparinux Sodium Injection

AHFS DI Essentials™. © Copyright 2022, Selected Revisions November 29, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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