Generic Name: Fondaparinux Sodium
Class: Direct Factor Xa Inhibitors
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

Warning(s)

  • Spinal/Epidural Hematoma Risk
  • Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of fondaparinux, low molecular weight heparins (LMWHs), or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture.1 16

  • Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet inhibitors, other anticoagulants).1

  • Risk also increased by history of traumatic or repeated epidural or spinal puncture or history of spinal deformity or spinal surgery.1 3 4

  • Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.1

  • Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants.1 (See Neurologic Effects under Cautions and also see Interactions.)

Introduction

Anticoagulant; a synthetic activated factor Xa inhibitor.

Uses for Arixtra

Thromboprophylaxis in Major Orthopedic Surgery

Prevention of postoperative DVT and PE in patients undergoing hip-fracture, hip-replacement, or knee-replacement surgery.1 2 3 4 5 6 10 1003

Used for extended prophylaxis (i.e., approximately 3 weeks beyond the perioperative period) in patients undergoing hip-fracture surgery.1 18

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; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.1003

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin [referring throughout this monograph to unfractionated heparin], warfarin, aspirin) are recommended by ACCP for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery.1003

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, bleeding risk, logistics, and compliance issues.1003

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing general (e.g., abdominal) surgery who are at risk for thromboembolic complications.1

ACCP recommends pharmacologic and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.1002 In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.1002

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If pharmacologic prophylaxis is indicated in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin is preferred; fondaparinux may be considered when both an LMWH and heparin are contraindicated or not available.1002

ACCP states that the same recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.1002

Medical Conditions Associated with Thromboembolism

ACCP recommends fondaparinux as an option for thromboprophylaxis in acutely ill, hospitalized medical patients at increased risk of thrombosis.1001

In general, pharmacologic thromboprophylaxis is recommended only in such patients considered to be at high risk of venous thromboembolism.1001

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).1 20 1005

Recommended by ACCP as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT or PE.1005

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment.1005 IV heparin also may be preferred in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.1005

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 of ≥5 cm in length.1005

ST-Segment-Elevation MI (STEMI)

Has been used as an adjunct to thrombolysis in a limited number of patients with acute STEMI.25 32 ACC and AHA recommend use of fondaparinux (given as an initial IV injection followed by daily sub-Q injections) in the initial management of such patients.32 In patients being managed with PCI, fondaparinux should not be used as the sole anticoagulant during the procedure.994 (See PCI under Uses.)

Unstable Angina and Non-ST-Segment-Elevation MI (NSTEMI)

Has been used as an alternative to heparin or an LMWH in the management of non-ST-segment-elevation acute coronary syndromes (unstable angina or NSTEMI).991

Administer anticoagulant therapy as soon as possible after hospital admission.991

In patients in whom an invasive management strategy is planned, ACC, AHA, and the American College of Cardiology Foundation (ACCF) recommend use of enoxaparin, heparin, bivalirudin, or fondaparinux for anticoagulant therapy.991 In patients undergoing PCI, fondaparinux should not be used as the sole anticoagulant during the procedure.994 (See PCI under Uses.)

In patients being managed with a conservative medical therapy strategy, recommended anticoagulants include enoxaparin, heparin, or fondaparinux; fondaparinux is preferred in patients with increased risk of bleeding.991

PCI

Used in patients undergoing PCI to prevent thrombus formation during the procedure; however, should not be used as the sole anticoagulant to support PCI.994 Increased risk of catheter-related thrombosis observed in patients receiving fondaparinux alone during primary PCI; additional use of an anticoagulant possessing anti-factor IIa activity (e.g., heparin) is recommended.991 994

Heparin-induced Thrombocytopenia

Has been used for treatment of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis syndrome (HITTS).1006

Although limited data suggest possible effectiveness in the management of HIT or HITTS, ACCP recommends the use of other nonheparin anticoagulants such as lepirudin or argatroban because of more extensive data.1006

ACCP suggests that fondaparinux may be used in patients with a history of HIT who experience acute thromboembolism (not related to HIT) until transition to warfarin can be achieved.1006

Arixtra Dosage and Administration

General

  • Evaluate the possibility of an underlying bleeding disorder before initiation of treatment.16 Since coagulation parameters are insensitive for monitoring fondaparinux activity, routine monitoring of such parameters is not required.1 16

Administration

Administer by sub-Q injection; do not give IM.1

Has been administered by direct IV injection initially in the treatment of acute STEMI.32

Patients should be sitting or supine during administration.16

Increased risk of major bleeding if administered <6 hours after surgery.1

Sub-Q Administration

Administer by sub-Q injection into fatty tissue, alternating injection sites daily (e.g., between the left and right anterolateral or posterolateral abdominal wall).1 16

Insert the entire length of the needle into a skin fold created by the thumb and forefinger; hold the skin fold, and push the plunger of the syringe the full length of the syringe barrel.1 16 Release the plunger, and the needle automatically withdraws from the skin and retracts into the security sleeve.1 16

Dosage

Dosages for fondaparinux sodium and heparin, heparinoids, or LMWHs cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis1 as they differ in the manufacturing process, anti-factor Xa and antithrombin activity, and dosage.1 10

The activity of fondaparinux sodium is measured based on plasma drug concentrations quantified by anti-Factor Xa activity using fondaparinux as the calibrator.1

Dosage of fondaparinux sodium is expressed in terms of the salt.1

Adults

Hip-Fracture, Hip-Replacement, or Knee-Replacement Surgery
Prophylaxis of DVT and PE
Sub-Q

Patients weighing ≥50 kg: 2.5 mg once daily.1 Manufacturer recommends that initial dose be given no earlier than 6–8 hours after surgery, provided hemostasis has been established.1 Avoid use in patients weighing <50 kg.1 (See Contraindications.)

Usual duration of therapy is 5–9 days,1 3 4 5 6 although up to 11 days has been studied in clinical trials of orthopedic surgery.1 16

Extended prophylaxis: Extended thromboprophylaxis for up to 35 days is recommended in patients undergoing hip fracture surgery,40 1003 and suggested for patients undergoing other major orthopedic procedures.1003

General Surgery
Prophylaxis of DVT and PE in 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.1 26 Avoid use in patients weighing <50 kg.1 (See Contraindications.)

Usual duration of therapy is 5–9 days, although up to 10 days has been studied.1

DVT and PE
Treatment
Sub-Q

Patients weighing <50 kg: 5 mg once daily.1

Patients weighing 50–100 kg: 7.5 mg once daily.1

Patients weighing >100 kg: 10 mg once daily.1

Usual duration of therapy is 5–9 days, although up to 26 days of treatment has been used.1

Initiate concurrent warfarin as soon as possible,1 usually within 72 hours of fondaparinux injection;1 20 ACCP recommends initiating warfarin simultaneously on the first day of fondaparinux treatment.1005

Continue fondaparinux and warfarin for ≥5 days and until an adequate response to warfarin is achieved (i.e., a stable INR of 2–3);1 ACCP recommends continuing concomitant therapy for ≥5 days and until INR of 2–3 has been maintained for ≥24 hours.1 1005

Unstable Angina/NSTEMI
Sub-Q

2.5 mg sub-Q once daily has been used.991

STEMI
IV, then Sub-Q

Has been administered at an initial dose of 2.5 mg as a single dose by direct IV injection, followed by 2.5 mg sub-Q once daily for the duration of hospitalization or up to 8 days.32

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment.1 Pharmacokinetics not evaluated in patients with severe hepatic impairment.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Contraindicated in patients with severe renal impairment (Clcr <30 mL/minute or Scr ≥3); increased risk for major bleeding episodes.1 32 Exercise caution in patients with other degrees of renal impairment.1

Low Body Weight

Use with caution and decrease dosage to 5 mg once daily for the treatment of DVT or PE in patients weighing <50 kg.1 Contraindicated for prophylaxis of DVT or PE in patients with body weight <50 kg undergoing hip-fracture, hip-replacement, knee-replacement, or abdominal surgery; increased incidence of major bleeding.1

Geriatric Patients

No specific dosage recommendations; however, careful attention to dosage directions recommended.1 (See Specific Populations under Cautions.)

Cautions for Arixtra

Contraindications

  • Patients with severe renal impairment (Clcr <30 mL/minute or Scr ≥3).1 32

  • Prophylactic use in patients undergoing hip-fracture, hip-replacement, knee-replacement, or abdominal surgery who weigh <50 kg.1

  • Active major bleeding, bacterial endocarditis, or thrombocytopenia associated with a positive in vitro test for antiplatelet antibody (HIT) in the presence of the drug.1 3 4 10 16

Warnings/Precautions

Warnings

Neurologic Effects

Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of fondaparinux and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.1 16 (See Boxed Warning.) Frequent monitoring for signs of neurologic impairment recommended.1 Some experts suggest that anticoagulant prophylaxis with fondaparinux be avoided in patients receiving epidural analgesia.3 4

Hematologic Effects

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).1 3 4 Use with caution in the treatment of DVT or PE in patients who weigh <50 kg.1 Use with caution in patients with moderate renal insufficiency (Clcr 30–50 mL/minute).1

Periodic routine blood counts, including platelet counts, and tests for occult blood in stool recommended.1

Avoid concomitant use of drugs that increase risk of bleeding unless essential for management of underlying condition (e.g., concomitant use of vitamin K antagonists for treatment of venous thromboembolism).1 Closely monitor for signs and symptoms of bleeding.1

Do not administer earlier than 6–8 hours after surgery because of increased risk of major bleeding.1

Moderate thrombocytopenia (platelet counts of 50,000–100,000/mm3) and severe thrombocytopenia (platelet counts <50,000/mm3) reported.1 Fondaparinux unlikely to cause HIT;2 11 12 13 however, isolated cases of thrombocytopenia with thrombosis resembling HIT reported during postmarketing experience.1 Manufacturer recommends monitoring thrombocytopenia of any degree closely and discontinuing fondaparinux if platelet counts fall below 100,000/mm3.1

Patients with Prosthetic Heart Valves

Cases of valve thrombosis resulting in death and/or requiring surgical intervention reported with low molecular weight heparin (e.g., enoxaparin) therapy in patients with prosthetic heart valves; some cases included pregnant women, and maternal and/or fetal deaths have been reported.15 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.16

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.1 24 30 31 The needle cover of the diluent syringe should not be handled by individuals sensitive to latex.1 24 30 31

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Manufacturer states to use caution.1 ACCP suggests the use of alternative anticoagulants in nursing women.1012

Pediatric Use

Safety and efficacy not established in children <17 years of age.1 16

Geriatric Use

Use with caution.1 No substantial differences in efficacy relative to younger adults.1 16 Possible increased major bleeding or other serious adverse effects in patients ≥75 years of age compared with younger adults.1 16 Substantially eliminated by kidneys; assess renal function periodically since geriatric patients are more likely to have decreased renal function.1 Careful attention to dosage directions and concomitant therapy (particularly platelet-aggregation inhibitors) is advised.1

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.1 Pharmacokinetics not studied in patients with severe hepatic impairment.1

Increased risk of hemorrhage; closely monitor for signs and symptoms of bleeding.1 (See Hematologic Effects under Cautions.)

Renal Impairment

Use with caution in those with moderate renal impairment (Clcr 30–50 mL/minute); increased risk of hemorrhage.1 16 Contraindicated in patients with severe renal impairment (Clcr <30 mL/minute or Scr ≥3).1 16 32 Assess renal function periodically (e.g., serum creatinine determinations).1 Discontinue immediately in patients who develop severe renal impairment during therapy.1

Common Adverse Effects

Patients undergoing hip-fracture, hip- or knee-replacement surgery: Anemia, fever, nausea, edema, constipation, rash, vomiting, insomnia, increased wound drainage, hypokalemia, urinary tract infection, dizziness, purpura, hypotension, confusion, bullous eruption, urinary retention, hematoma, major bleeding, diarrhea, dyspepsia, postoperative hemorrhage, headache.1 16

Patients undergoing abdominal surgery: Postoperative wound infection, postoperative hemorrhage, fever, surgical site reaction, anemia, hypertension, pneumonia, vomiting.1

Venous thromboembolism: Constipation, headache, insomnia, fever, nausea, urinary tract infection, coughing.1

Interactions for Arixtra

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

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.1

Protein-bound Drugs

Pharmacokinetic interaction unlikely.1

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral

Increased risk of bleeding1

Discontinue oral anticoagulants prior to initiation of fondaparinux1 40

If coadministration is essential, monitor patients closely1 40

Digoxin

Pharmacokinetic/pharmacodynamic interaction unlikely1 16

NSAIAs

Increased risk of bleeding1

Discontinue NSAIAs prior to initiation of fondaparinux1 40

If coadministration is essential, monitor patients closely40

Platelet-aggregation inhibitors

Increased risk of bleeding1

Discontinue platelet-aggregation inhibitors prior to initiation of fondaparinux1 40

If coadministration is essential, monitor patients closely1 40

Arixtra Pharmacokinetics

Absorption

Bioavailability

Sub-Q: Absolute bioavailability 100%.1 10 41

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).1

Special Populations

In patients with renal impairment, anticoagulant effects may persist for >2–4 days following discontinuance of therapy.1

Distribution

Extent

In healthy adults, distributes mainly in blood and only to a minor extent in extravascular fluid.1 Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

In vitro, 94% bound to antithrombin III.1

Elimination

Metabolism

Most of dose not metabolized.1

Elimination Route

Eliminated unchanged in urine in individuals with normal renal function.1 41

Half-life

17–21 hours.1

Special Populations

In patients with renal impairment, the total clearance is reduced by 25, 40, and 55% in patients with mild, moderate, and severe renal impairment, respectively, compared with those with normal renal function.1

In geriatric patients >75 years of age, total clearance is approximately 25% lower compared with patients <65 years of age.1

In dialysis-dependent patients, approximately 20% of the drug is removed by hemodialysis.1

In patients weighing <50 kg, total clearance is reduced by approximately 30%.1

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).1

Compatibility

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

Do not mix with other injections or infusions.1

Actions

  • Anticoagulation results from rapid inhibition of factor Xa by antithrombin III bound to fondaparinux (about 300-fold greater than innate activity).1 2 4 10 Neutralization of coagulation factor Xa inhibits the conversion of prothrombin to thrombin and subsequent thrombus formation.1 2 4 10 Unable to lyse established thrombi.16

  • Binds selectively to antithrombin III; unable to inactivate thrombin.1 2 4 16 At the recommended dosage, fibrinolytic activity not affected.1

  • Platelet function or global clotting function tests (e.g., PT, bleeding time, aPTT) generally not affected when administered at the recommended dosage.1 10 16

Advice to Patients

  • Importance of initiating self-administration only if a clinician determines that the such administration is appropriate and that medical follow-up is available as necessary.1 Importance of appropriate training in injection technique.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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)

GlaxoSmithKline

5 mg/0.4 mL

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

GlaxoSmithKline

7.5 mg/0.6 mL

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

GlaxoSmithKline

10 mg/0.8 mL

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

GlaxoSmithKline

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. GlaxoSmithKline. Arixtra (fondaparinux sodium) injection prescribing information. Research Triangle Park, NC: 2010 Mar.

2. Turpie AGG, Gallus AS, Hoek JA, for the Pentasaccharide Investigators. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001; 344:619-25. [IDIS 459860] [PubMed 11228275]

3. Eriksson BI, Bauer KA, Lassen MR et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip- fracture surgery. N Engl J Med. 2001; 345:1298-304. [IDIS 471305] [PubMed 11794148]

4. Bauer KA, Eriksson BI, Lassen MR et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001; 345:1305-10. [IDIS 471306] [PubMed 11794149]

5. Lassen MR, Bauer KA, Eriksson BI et al. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: A randomized double-blind comparison.Lancet 2002; 359:715-20.

6. Turpie GG, Bauer KA, Eriksson BI et al.. Postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: A randomized double-blind trial. Lancet 2002; 359:1721-6. [IDIS 481278] [PubMed 12049860]

10. Bauer KA. Fondaparinux sodium: a selective inhibitor of factor Xa. Am J Health-Syst Pharm. 2001; 58 (Suppl.2):S14-7. [IDIS 472189] [PubMed 11715834]

11. Rosenberg RD. Redesigning heparin. N Engl J Med. 2001; 344:673-4. Editorial. [IDIS 459863] [PubMed 11228284]

12. Ahmad S, Jeske WP, Walenga JM et al. Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. Clin Appl Thromb Hemost. 1999; 5:259-66. [PubMed 10726024]

13. Amiral J, Lormeau JC, Marfaing-Koka A et al. Absence of cross- reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis. 1997; 8:114-7. [PubMed 9518042]

14. Hull R, Pineo G. A synthetic pentasaccharide for the prevention of deep- vein thrombosis. N Engl J Med. 2001; 345:291. Letter. [IDIS 467250] [PubMed 11474672]

15. Aventis. Lovenox (enoxaparin sodium) injection prescribing information. Bridgewater, NJ; 2001 Jul.

16. Organon Sanofi-Synthelabo, West Orange, NJ: Personal communication.

17. Bounameaux, H, Perneger T. Fondaparinux: A new synthetic pentasaccharide for thrombosis prevention. Lancet.2002; 359:1710-1.

18. Eriksson BI, Lassen MR. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2003; 163:1337-42. [IDIS 499798] [PubMed 12796070]

20. Buller HR, Davidson BL, Decousus H et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004; 140:867-73. [IDIS 516440] [PubMed 15172900]

21. Buller HR, Davidson BL, Decousus H et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003; 349:1695-702. [IDIS 505897] [PubMed 14585937]

23. Organon Sanofi-Synthelabo. Arixtra (fondaparinux sodium) injection prescribing information. West Orange, NJ: 2001 Dec.

24. Food and Drug Administration. Natural rubber-containing medical devices; user labeling. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1997; 62:51021-30.

25. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004; 44(3):671-719. [PubMed 15358045]

26. Agnelli G, Bergvist D, Cohen AT et al. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005; 92:1212-20. [PubMed 16175516]

30. Food and Drug Administration. Amended economic impact analysis of final rule requiring use of labeling on natural rubber containing devices. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1998; 63:50660-704.

31. Food and Drug Administration. Latex-containing devices; user labeling. 21 CFR Part 801. Proposed rule. (Docket No. 96N-0119) Fed Regist. 1996; 61:32617-21.

32. Antman EM, Anbe DT, Armstrong PW et al. 2007 Focused Update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction). J Am Coll Cardiol. 2008; 51:210–47.

34. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006; 354:1464-76. [PubMed 16537663]

35. Mehta SR, Granger CB, Eikelboom JW et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007; 50:1742-51. [PubMed 17964037]

40. GlaxoSmithKline. Arixtra (fondaparinux sodium) injection prescribing information. Research Triangle Park, NC: 2011 Feb.

41. Donat F, Duret JP, Santoni A et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 2002; 41 Suppl 2:1-9. [PubMed 12383039]

991. Anderson JL, Adams CD, Antman EM et al. 2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123:e426-579.

994. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011; 58:e44-122. [PubMed 22070834]

1001. Kahn SR, Lim W, Dunn AS et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e195S-226S.

1002. Gould MK, Garcia DA, Wren SM et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e227S-77S. [PubMed 22315263]

1003. Falck-Ytter Y, Francis CW, Johanson NA et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e278S-325S. [PubMed 22315265]

1005. Kearon C, Akl EA, Comerota AJ et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e419S-94S. [PubMed 22315268]

1006. Linkins LA, Dans AL, Moores LK et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e495S-530S.

1012. Bates SM, Greer IA, Middeldorp S et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e691S-736S. [PubMed 22315276]

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