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Fondaparinux

Generic name: fondaparinux systemic

Brand names: Arixtra, Arixtra 5 mg/dose, Arixtra 7.5 mg/dose, Arixtra 10 mg/dose

Boxed Warning

Spinal/Epidural hematomas:

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins, heparinoids, or fondaparinux and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants; a history of traumatic or repeated epidural or spinal puncture; or a history of spinal deformity or spinal surgery. Optimal timing between the administration of fondaparinux and neuraxial procedures is not known.

Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary.

Consider the benefit and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous, as sodium:

Generic: 2.5 mg/0.5 mL (0.5 mL); 5 mg/0.4 mL (0.4 mL); 7.5 mg/0.6 mL (0.6 mL); 10 mg/0.8 mL (0.8 mL)

Solution, Subcutaneous, as sodium [preservative free]:

Arixtra: 2.5 mg/0.5 mL (0.5 mL); 5 mg/0.4 mL (0.4 mL); 7.5 mg/0.6 mL (0.6 mL); 10 mg/0.8 mL (0.8 mL)

Generic: 2.5 mg/0.5 mL (0.5 mL); 5 mg/0.4 mL (0.4 mL); 7.5 mg/0.6 mL (0.6 mL); 10 mg/0.8 mL (0.8 mL)

Pharmacology

Mechanism of Action

Fondaparinux is a synthetic pentasaccharide that causes an antithrombin III-mediated selective inhibition of factor Xa. Neutralization of factor Xa interrupts the blood coagulation cascade and inhibits thrombin formation and thrombus development.

Pharmacokinetics/Pharmacodynamics

Absorption

SubQ: Rapid and complete

Distribution

Vd: 7 to 11 L; mainly in blood

Excretion

Urine (up to 77%, unchanged drug)

Time to Peak

SubQ: ~2 to 3 hours

Half-Life Elimination

17 to 21 hours; prolonged with renal impairment and in the elderly

Protein Binding

≥94% to antithrombin III

Use in Specific Populations

Special Populations: Renal Function Impairment

Elimination is prolonged.

Special Populations: Hepatic Function Impairment

In patients with moderate hepatic impairment (Child-Pugh class B), Cmax and AUC were decreased by 22% and 39%, respectively.

Special Populations: Elderly

Elimination is prolonged in patients older than 75 years.

Special Populations Note

Body weight: Total clearance is decreased approximately 30% in patients weighing less than 50 kg.

Use: Labeled Indications

Deep vein thrombosis: Treatment of acute deep vein thrombosis in conjunction with warfarin.

Pulmonary embolism: Treatment of acute pulmonary embolism in conjunction with warfarin.

Venous thromboembolism prophylaxis in surgical patients: Prophylaxis of venous thromboembolism in patients undergoing surgery for hip replacement, knee replacement, hip fracture (including extended prophylaxis following hip fracture surgery), or abdominal surgery (in patients at risk for thromboembolic complications).

Use: Off Label

Acute coronary syndromeayes

Non ST-elevation acute coronary syndrome (NSTE-ACS): Data from a randomized, double-blind, double-dummy trial comparing fondaparinux and enoxaparin demonstrated that fondaparinux is similar to enoxaparin in reducing the risk of ischemic events, major bleeding, and improves long-term mortality and morbidity Yusuf 2006a.

ST-Elevation myocardial infarction: Data from a randomized, double-blind, clinical trial comparing fondaparinux with placebo, demonstrated that fondaparinux significantly reduces mortality and re-infarction, especially in patients not undergoing primary percutaneous coronary intervention (PCI), without increasing bleeding and strokes Yusuf 2006b.

Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non ST-elevation acute coronary syndrome (NSTE-ACS) and the 2013 American College of Cardiology Foundation/AHA guidelines for the management of ST-elevation myocardial infarction (STEMI), fondaparinux is effective and recommended as an alternative to unfractionated heparin or enoxaparin for the treatment of patients presenting with NSTE-ACS or STEMI.

Acute symptomatic superficial vein thrombosis (≥5 cm in length) of the legsayes

Data from a randomized, double-blind, placebo-controlled trial support the use of fondaparinux in the treatment of this condition Decousus 2010.

Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic therapy for venous thromboembolism (VTE), fondaparinux is effective and recommended for use in patients with acute symptomatic superficial vein thrombosis (≥5 cm in length) of the legs.

Heparin-induced thrombocytopenia treatmentcyes

Data from a retrospective, observational, multicenter registry study of hospitalized patients with a diagnosis of heparin-induced thrombocytopenia (HIT) who received treatment with ≥1 dose of a nonheparin anticoagulant suggest that fondaparinux may be beneficial for treatment of patients with this condition Schindewolf 2017. Several case series Goldfarb 2011, Grouzi 2010, Lobo 2008, Warkentin 2011 and another retrospective observational study Kang 2015 also report the use of fondaparinux for treatment of patients with HIT.

Based on the American Society of Hematology 2018 guidelines for management of VTE: HIT, fondaparinux is an effective and recommended agent for HIT complicated by thrombosis or HIT without thrombosis (isolated HIT).

Venous thromboembolism prophylaxis in medical patients with acute illnessyes

Based on the 2018 American Society of Hematology guidelines for management of VTE: prophylaxis for hospitalized and nonhospitalized medical patients, fondaparinux is an effective and recommended agent for VTE prophylaxis in acutely ill medical patients.

Venous thromboembolism prophylaxis in patients undergoing major surgery for canceryes

Based on the 2019 American Society of Clinical Oncology clinical practice guideline update for VTE prophylaxis and treatment in patients with cancer, fondaparinux may be considered as an option for pharmacologic thromboprophylaxis in patients undergoing major surgery for cancer, unless contraindicated due to high risk of bleeding or active bleeding.

Contraindications

Serious hypersensitivity (eg, angioedema, anaphylactoid/anaphylactic reactions) to fondaparinux or any component of the formulation; severe renal impairment (CrCl <30 mL/minute); body weight <50 kg (prophylaxis); active major bleeding; bacterial endocarditis; thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of fondaparinux

Dosage and Administration

Dosing: Adult

Note: Prothrombin time and activated partial thromboplastin time are insensitive measures of fondaparinux activity. If unexpected changes in coagulation parameters or major bleeding occur, discontinue fondaparinux.

Acute coronary syndrome (off-label use):

Non ST-elevation acute coronary syndrome: SubQ: 2.5 mg once daily; treat for the duration of hospitalization or until percutaneous coronary intervention (PCI) performed (ACC/AHA [Amsterdam 2014]).

ST-elevation myocardial infarction: IV: 2.5 mg once; subsequent doses (starting the following day): SubQ: 2.5 mg once daily; treat for the duration of the hospitalization, up to 8 days, or until revascularization (ACCF/AHA [O’Gara 2013]; Yusuf 2006b).

Acute symptomatic superficial vein thrombosis (≥5 cm in length) of the legs (off-label use): SubQ: 2.5 mg once daily for 45 days (ACCP [Kearon 2012]; Decousus 2010).

Deep vein thrombosis and/or pulmonary embolism treatment:

Note: Fondaparinux may be used in patients with a history of heparin-induced thrombocytopenia (HIT) (ACCP [Linkins 2012]; Warkentin 2011a). For timing of initiating oral anticoagulant, see Transitioning Between Anticoagulants below.

SubQ:

<50 kg: 5 mg once daily.

50 to 100 kg: 7.5 mg once daily.

>100 kg: 10 mg once daily.

Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding, and individual preference.

Provoked venous thromboembolism (VTE): 3 months (provided the provoking risk factor is no longer present) (ACCP [Kearon 2016]).

Unprovoked pulmonary embolism (PE) or deep vein thrombosis (DVT) (proximal or isolated distal): ≥3 months depending on risk of VTE recurrence and bleeding (ACCP [Kearon 2012]; ACCP [Kearon 2016]; ISTH [Baglin 2012]).

Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals (ACCP [Kearon 2016]).

Heparin-induced thrombocytopenia treatment (alternative agent) (off-label use): Note: For initial therapy of acute HIT in selected hemodynamically stable patients (ASH [Cuker 2018]; Grouzi 2010; Lobo 2008; Warkentin 2011b): SubQ:

<50 kg: 5 mg once daily.

50 to 100 kg: 7.5 mg once daily.

>100 kg: 10 mg once daily.

Duration: Although not well defined, a total minimum duration of 4 weeks is typically used for patients without thrombosis; a minimum duration of 3 months is used for patients who have HIT-associated thrombosis (ACCP [Linkins 2012]). In patients without thrombosis, some experts suggest anticoagulation until platelet count recovery, allowing potentially for a shorter duration (ASH [Cuker 2018]).

Venous thromboembolism prophylaxis:

Note: Fondaparinux may be used in patients with a history of HIT (ASH [Cuker 2018]; Blackmer 2009; Harenberg 2004; Parody 2003).

Medical patients with acute illness at moderate and high risk for venous thromboembolism (off-label use): SubQ: 2.5 mg once daily; continue for length of hospital stay or until patient is fully ambulatory and risk of VTE has diminished (ACCP [Kahn 2012]; ASCO [Key 2019]; Blackmer 2009; Cohen 2006; Harenberg 2004; Parody 2003).

Major surgery for cancer (off-label use): SubQ: 2.5 mg once daily beginning 6 to 8 hours postoperatively. The optimal duration of prophylaxis has not been established; usually given for a minimum of 7 to 10 days. Extending for up to 4 weeks may be considered in patients undergoing major abdominal or pelvic surgery (ASCO [Key 2019]).

Surgical patients (without cancer): SubQ: ≥50 kg: 2.5 mg once daily beginning after hemostasis has been established, no earlier than 6 to 8 hours postoperatively. Note: Prophylactic use contraindicated in patients <50 kg.

Duration in nonorthopedic surgery: Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (ACCP [Gould 2012]; Pai 2019a).

Duration in orthopedic surgery: Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days; some experts suggest a duration in the lower end of the range (eg, 10 to 14 days) for total knee arthroplasty or higher end of range (eg, ~30 days) for total hip arthroplasty (Falck-Ytter 2012; Pai 2019b). For extended prophylaxis, may transition to an oral anticoagulant (Pai 2019b).

Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; refer to label and local protocol for additional detail:

Transitioning from fondaparinux to another anticoagulant:

Transitioning from fondaparinux to unfractionated heparin (UFH) continuous infusion: Start maintenance dose (no bolus) of unfractionated heparin 1 to 2 hours prior to when the next dose of fondaparinux is scheduled to be given (Nutescu 2007).

Transitioning from fondaparinux to non-warfarin oral anticoagulant (NOAC): Start NOAC within 0 to 2 hours of when the next dose of fondaparinux is scheduled to be given (Burnett 2016; Smythe 2016).

Transitioning from fondaparinux to warfarin: Overlap fondaparinux and warfarin until a therapeutic INR has been established. For acute DVT and PE treatment, INR should be ≥2 for at least 24 hours and parenteral therapy should be continued for at least 5 days for initial treatment (ACCP [Guyatt 2012]; Smythe 2016).

Transitioning from another anticoagulant to fondaparinux:

Transitioning from UFH continuous infusion to fondaparinux: Start fondaparinux within one hour after UFH continuous infusion has been stopped (Nutescu 2007) (consult local protocol if aPTT is above the target range).

Transitioning from NOAC to fondaparinux: Start fondaparinux at the time when the next dose of NOAC would have been given (Bauer 2018).

Transitioning from warfarin to fondaparinux: Discontinue warfarin and initiate fondaparinux as soon as INR becomes subtherapeutic (Bauer 2018).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Deep vein thrombosis (DVT), treatment: Limited data available: Children and Adolescents: SubQ: 0.1 mg/kg/dose once daily; dosing based on 2 pediatric studies including a prospective dose-finding, pharmacokinetic, and safety study in patients (n=24, age: 1 to 18 years) receiving primary treatment for DVT (n=23) or heparin-induced thrombocytopenia (n=1) and a consecutive cohort study evaluating long-term safety, dosing, and efficacy (n=35, age: 9.11 ± 0.95 years [range: 1 to 17 years]) (Ko 2014; Young 2011).

Dose adjustment for DVT treatment: Titrate dose to achieve a 3- to 4-hour postdose target fondaparinux Antifactor Xa level of 0.5 to 1 mg/L (Ko 2014; Young 2011; Young 2017).

Fondaparinux Dose Titration

Fondaparinux Antifactor Xa Level

Dose Titration

Modified from Young G, Lee DL, O'Brien SH et al. FondaKIDS: A prospective pharmacokinetic and safety study of fondaparinux in children between 1 and 18 years of age. Pediatr Blood Cancer. 2011;57:1049-1054.

<0.3 mg/L

Increase dose by 0.03 mg/kg

0.3 to 0.49 mg/L

Increase dose by 0.01 mg/kg

0.5 to 1 mg/L

Keep same dosage

1.1 to 1.2 mg/L

Decrease dose by 0.01 mg/kg

>1.2 mg/L

Decrease dose by 0.03 mg/kg

Table has been converted to the following text:

Fondaparinux Dose Titration:

Fondaparinux Antifactor Xa level <0.3 mg/L: Increase dose by 0.03 mg/kg.

Fondaparinux Antifactor Xa level 0.3 to 0.49 mg/L: Increase dose by 0.01 mg/kg.

Fondaparinux Antifactor Xa level 0.5 to 1 mg/L: Keep same dosage.

Fondaparinux Antifactor Xa level 1.1 to 1.2 mg/L: Decrease dose by 0.01 mg/kg.

Fondaparinux Antifactor Xa level >1.2 mg/L: Decrease dose by 0.03 mg/kg.

Reconstitution

IV administration (off-label route): May mix with 25 mL or 50 mL NS (Arixtra Canadian product labeling).

Administration

SubQ: For SubQ administration; do not administer IM. Alternate injection sites. Do not expel air bubble from syringe before injection. Administer according to recommended regimen; when used for DVT prophylaxis, early initiation (before 6 hours after orthopedic surgery) has been associated with increased bleeding.

IV: For STEMI patients (off-label use) may administer initial dose as IV push or mix in NS and infuse over 1 to 2 minutes; flush tubing with NS after infusion to ensure complete administration for fondaparinux.

To convert from IV unfractionated heparin (UFH) infusion to SubQ fondaparinux (Nutescu 2007): Calculate specific dose for fondaparinux based on indication, discontinue UFH, and begin fondaparinux within 1 hour

To convert from SubQ fondaparinux to IV UFH infusion (Nutescu 2007): Discontinue fondaparinux; calculate specific dose for IV UFH infusion based on indication; omit heparin bolus/loading dose

For subQ fondaparinux dosed every 24 hours: Start IV UFH infusion 22 to 23 hours after last dose of fondaparinux

Storage

Store at 20°C to 25°C (68°F to 77°F). For IV infusion (off-label route), use immediately once diluted in NS; can also be stored for up to 24 hours at 15°C to 30°C (59°F to 86°F) (Arixtra Canadian product labeling).

Drug Interactions

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds). Consider therapy modification

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Test Interactions

International standards of heparin or LMWH are not the appropriate calibrators for antifactor Xa activity of fondaparinux.

Adverse Reactions

As with all anticoagulants, bleeding is the major adverse effect. Hemorrhage may occur at any site. Risk appears increased by a number of factors including renal dysfunction, age (>75 years), and weight (<50 kg).

>10%: Hematologic & oncologic: Anemia (2% to 20%)

1% to 10%:

Cardiovascular: Hypotension (≤4%)

Central nervous system: Insomnia (≤5%), dizziness (≤4%), confusion (1% to 3%)

Dermatologic: Increased wound secretion (≤5%), skin blister (≤3%)

Endocrine & metabolic: Hypokalemia (≤4%)

Hematologic & oncologic: Purpura (≤4%), thrombocytopenia (50,000 to 100,000/mm3: 3%), hematoma (2% to 3%), minor hemorrhage (2% to 3%), major hemorrhage (1% to 3%; risk of major hemorrhage increased as high as 5% in patients receiving initial dose <6 hours following surgery), postoperative hemorrhage (≤2%)

Hepatic: Increased serum ALT (>3 × ULN: 1% to 3%), increased serum AST (>3 × ULN: <1% to ≤2%)

Infection: postoperative wound infection (abdominal surgery: 5%)

Respiratory: Epistaxis (VTE: 1%)

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, angioedema, catheter site thrombosis (during PCI; without heparin), elevated aPTT associated with bleeding, epidural hematoma, hemorrhagic death, injection site reaction (bleeding at injection site, skin rash, pruritus), intracranial hemorrhage, reoperation due to bleeding, severe thrombocytopenia (<50,000/mm3), spinal hematoma, thrombocytopenia (with thrombosis)

Warnings/Precautions

Concerns related to adverse effects:

  • Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative and angiodysplastic GI disease; uncontrolled arterial hypertension; hemorrhagic stroke; recent intracranial hemorrhage; use shortly after brain, spinal, or ophthalmology surgery; in patients treated concomitantly with platelet inhibitors; thrombocytopenia or platelet defects; renal impairment; diabetic retinopathy; and/or patients <50 kg. Risk of major bleeding may be increased if initial dose is administered earlier than recommended (initiation recommended at 6 to 8 hours following surgery). Do not administer with other agents that increase the risk of hemorrhage unless they are essential for the management of the underlying condition (eg, vitamin K antagonists for treatment of venous thromboembolism). Prothrombin time and activated partial thromboplastin time (aPTT) are insensitive measures of fondaparinux activity. If unexpected changes in coagulation parameters or major bleeding occur, discontinue fondaparinux (elevated aPTT associated with bleeding events have been reported in postmarketing data). No specific antidote for fondaparinux exists.
  • Thrombocytopenia: Has occurred with administration, including very rare reports of thrombocytopenia with thrombosis similar to heparin-induced thrombocytopenia (HIT); however, has been used in patients with current or history of HIT due to a lack of an immune-mediated effect on platelets (ACCP [Guyatt 2012]; Savi 2005). Use is contraindicated in patients with thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of fondaparinux. Monitor patients closely and discontinue therapy if platelets fall to <100,000/mm3.

Disease-related concerns:

  • Hepatic impairment: May increase the risk of bleeding in patients with hepatic impairment. Use with caution.
  • Renal impairment: May increase the risk of bleeding in patients with renal impairment. Use with caution in patients with CrCl 30 to 50 mL/minute (may cause prolonged anticoagulation); contraindicated in patients with CrCl <30 mL/minute. Periodically monitor renal function; discontinue immediately if severe renal impairment develops.

Concurrent drug therapy issues:

  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

  • Elderly: Use with caution in the elderly; increased risk of bleeding in patients >75 years of age.
  • Patients <50 kg: In patients <50 kg, clearance of fondaparinux is reduced by 30% and the risk of bleeding is increased; use is contraindicated in patients <50 kg when used as prophylactic therapy for patients undergoing hip fracture, hip replacement, or knee replacement surgery, or abdominal surgery; use with caution in the treatment of pulmonary embolism and deep vein thrombosis.

Dosage form specific issues:

  • Latex: The needle guard may contain natural latex rubber.

Other warnings/precautions:

  • Appropriate use: For subcutaneous administration; not for IM administration. For ST-elevation myocardial infarction patients (off-label use) may administer initial dose IV. Do not use interchangeably (unit for unit) with low molecular weight heparins, heparin, or heparinoids.
  • Discontinuation: Following discontinuation, the anticoagulant effects of fondaparinux may persist for 2 to 4 days and even longer in patients with renal impairment.
  • Neuraxial anesthesia: [US Boxed Warning]: Spinal or epidural hematomas, including subsequent long-term or permanent paralysis, may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture in patients anticoagulated with low-molecular-weight heparin, heparinoids, or fondaparinux. Consider risk versus benefit prior to spinal procedures; risk is increased by the use of concomitant agents which may alter hemostasis (such as nonsteroidal anti-inflammatory drugs, platelet inhibitors, or other anticoagulants), the use of indwelling epidural catheters, a history of spinal deformity or spinal surgery, as well as a history of traumatic or repeated epidural or spinal punctures. Optimal timing between administration of fondaparinux and neuraxial procedures is not known. Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary. Consider the benefit and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
  • Percutaneous coronary intervention (PCI): The administration of fondaparinux as the sole anticoagulant is not recommended during PCI due to an increased risk for guiding-catheter thrombosis. Use of an anticoagulant with antithrombin activity (eg, unfractionated heparin) is recommended as adjunctive therapy to PCI even if prior treatment with fondaparinux (must take into account whether GP IIb/IIIa antagonists have been administered) (ACC/AHA [Amsterdam 2014]; Levine 2011). Use of fondaparinux during primary PCI is not recommended.

Monitoring Parameters

Periodically monitor CBC, platelet count, serum creatinine, occult blood testing of stools, signs and symptoms of bleeding. Anti-Xa activity can be measured if the assay is specifically calibrated for fondaparinux.

In patients undergoing neuraxial procedures, monitor for signs/symptoms of neurologic impairment.

Pregnancy

Pregnancy Considerations

Based on case reports, small amounts of fondaparinux have been detected in the umbilical cord following multiple doses during pregnancy (Dempfle 2004). Use of fondaparinux in pregnancy should be limited to those women who have severe allergic reactions to heparin, including heparin-induced thrombocytopenia, and who cannot receive danaparoid (Guyatt 2012).

Patient Education

What is this drug used for?

  • It is used to thin the blood so that clots will not form.
  • It is used to treat blood clots.

Frequently reported side effects of this drug

  • Injection site irritation
  • Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
  • Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.
  • Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes.
  • Back pain
  • Numbness or tingling
  • Muscle weakness
  • Paralysis
  • Leaking of urine
  • Bowel incontinence
  • Dizziness
  • Passing out
  • A fall hitting head
  • Confusion
  • Severe headache
  • Burning or numbness feeling
  • Severe loss of strength and energy
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated February 9, 2020.