Version July 2025
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.
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. If PCI is performed, an alternative anticoagulant with antithrombin activity (ie, unfractionated heparin) is recommended during the procedure. Fondaparinux as the sole anticoagulant is not recommended during PCI due to an increased risk for guiding-catheter thrombosis (Ref).
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 PCI is performed. If PCI is performed, an alternative anticoagulant with antithrombin activity (ie, unfractionated heparin) is recommended during the procedure. Fondaparinux as the sole anticoagulant is not recommended during PCI due to an increased risk for guiding-catheter thrombosis (Ref).
Heparin-induced thrombocytopenia, treatment (alternative agent) (off-label use): Note: For initial therapy of acute HIT in selected hemodynamically stable patients (Ref):
<50 kg: SUBQ: 5 mg once daily.
50 to 100 kg: SUBQ: 7.5 mg once daily.
>100 kg: SUBQ: 10 mg once daily.
Duration: Not well established.
Heparin-induced thrombocytopenia without thrombosis: Typically, 4 weeks to 3 months (Ref). Alternatively, may discontinue anticoagulation after platelet count recovery, potentially resulting in a shorter duration (Ref).
Heparin-induced thrombocytopenia with thrombosis: Typically, 3 to 6 months (Ref).
Superficial vein thrombosis, acute symptomatic (off-label use):
Note: For use in patients at increased risk for thromboembolism or with recurrent superficial vein thrombosis.
SUBQ: 2.5 mg once daily for 45 days (Ref).
Venous thromboembolism, prophylaxis:
Note: Prophylactic use contraindicated in patients <50 kg. Fondaparinux may be used in patients with a history of HIT (Ref).
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 venous thromboembolism (VTE) has diminished (Ref).
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 (Ref).
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.
Duration in nonorthopedic surgery: Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (Ref).
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 (Ref). For extended prophylaxis, may transition to an oral anticoagulant (Ref).
Venous thromboembolism, treatment:
Note: In patients with active cancer (eg, metastatic disease or receiving chemotherapy) requiring parenteral anticoagulation, may use as an alternative if unable to use low molecular weight heparin or unfractionated heparin (eg, history of heparin-induced thrombocytopenia) (Ref). For timing of initiating oral anticoagulant, see "Transitioning Between Anticoagulants" below.
<50 kg: SUBQ: 5 mg once daily.
50 to 100 kg: SUBQ: 7.5 mg once daily.
>100 kg: SUBQ: 10 mg once daily.
Duration of therapeutic anticoagulation (first episode, general recommendations):
Provoked venous thromboembolism with a transient risk factor: 3 months with reassessment for resolution of the provoking factor (Ref).
Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of venous thromboembolism recurrence and bleeding (Ref).
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals (Ref).
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 (Ref).
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 (Ref).
Transitioning from fondaparinux to warfarin: Overlap fondaparinux and warfarin until a therapeutic INR has been established. INR should be ≥2 for at least 24 hours and parenteral therapy should be continued for at least 5 days for initial treatment (Ref).
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 (Ref) (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 (Ref).
Transitioning from warfarin to fondaparinux: Discontinue warfarin and initiate fondaparinux as soon as INR becomes subtherapeutic (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: SUBQ:
CrCl 50 to 80 mL/minute: No dosage adjustment necessary. However, total clearance reduced ~25% in patients with CrCl 50 to 80 mL/minute.
CrCl 30 to <50 mL/minute: No dosage adjustment necessary. However, use with caution and monitor closely for bleeding as accumulation can occur (Ref); total clearance reduced ~40% compared to patients with CrCl >80 mL/minute. Some experts would consider switching to an alternative anticoagulant (Ref).
When used for thromboprophylaxis, some experts recommend a 50% dose reduction or use of low-dose heparin instead of fondaparinux (Ref). Pharmacokinetic simulations and cohort studies suggest a 40% dose reduction (1.5 mg daily) (Ref).
CrCl <30 mL/minute: Use is contraindicated in the manufacturer's labeling. Total clearance is reduced ~55% compared to patients with CrCl >80 mL/minute.
Limited data suggest that the use of the 1.5 mg daily dose for thromboprophylaxis in patients with a CrCl of 20 to 50 mL/minute may be considered (Ref).
Hemodialysis, intermittent (thrice weekly): SUBQ: Avoid use. Although clearance may actually increase by 20% in patients receiving chronic intermittent hemodialysis, fondaparinux may accumulate (as shown by rising anti-Xa levels) with repeated dosing (Ref).
Peritoneal dialysis: SUBQ: Avoid use. Unlikely to be substantially cleared by peritoneal dialysis (Ref).
Mild-to-moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary; monitor for signs of bleeding.
Severe impairment (Child-Pugh class C): There are no dosage adjustment provided in the manufacturer's labeling (has not been studied). Use with caution; monitor closely for signs of bleeding.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1 and 2 obesity (BMI 30 to 39 kg/m2):
Treatment: No dosage adjustment necessary (Ref). Refer to adult dosing for indication-specific doses.
Venous thromboembolism prophylaxis: No dosage adjustment necessary (Ref). Refer to adult dosing for indication-specific doses.
Class 3 obesity (BMI ≥40 kg/m2):
Treatment: No dosage adjustment necessary (Ref). There is limited data available in patients with BMI >45 kg/m2 or >150 kg; other treatment options are suggested (Ref). Refer to adult dosing for indication-specific doses.
Venous thromboembolism prophylaxis: SUBQ: 5 mg once daily (Ref).
Rationale for recommendations: There are limited data in patients with obesity evaluating pharmacokinetics, changes in anti-Factor Xa levels, or outcomes when fondaparinux is used for prophylaxis or treatment. The clearance of fondaparinux increases nonproportionately with weight, resulting in potential decreased fondaparinux concentrations with increased weight (Ref). For prophylaxis, retrospective observational data in patients with BMI ≥40 kg/m2 receiving standard prophylactic dosing suggest 47% of measured anti-Factor Xa concentrations were below target goal (Ref). In bariatric surgery patients, higher prophylactic dose fondaparinux (5 mg SUBQ daily) resulted in ~74% of patients obtaining target anti-Factor Xa levels (Ref). For treatment, a subgroup analysis of a major comparative treatment study showed no difference in venous thromboembolism recurrence or major bleeding with standard treatment doses (Ref). This study evaluated patients who were over 100 kg (only ~11% of the original study population), however, suggests that standard treatment doses in patients with obesity are reasonable until further data are available (Ref).
Refer to adult dosing.
(For additional information see "Fondaparinux: Pediatric drug information")
Venous thromboembolism (VTE), treatment:
Initial:
Children and Adolescents:
<10 kg: Very limited data available: SUBQ: 0.1 mg/kg/dose once daily (Ref).
10 to 20 kg: SUBQ: 0.1 mg/kg/dose once daily. Note: Round dose to the nearest 0.1 mg.
>20 kg: SUBQ: 0.1 mg/kg/dose once daily, maximum daily dose: 7.5 mg/day; round dose to nearest prefilled syringe as follows:
>20 to 40 kg: SUBQ: 2.5 mg once daily.
>40 to 60 kg: SUBQ: 5 mg once daily.
>60 kg: SUBQ: 7.5 mg once daily.
Dose adjustment for VTE treatment: Titrate dose to achieve a 2- to 4-hour post-dose target fondaparinux-based antifactor Xa level of 0.5 to 1 mg/L.
|
Fondaparinux-based antifactor Xa level |
Dose adjustmenta |
|---|---|
|
a Round dose to the nearest 0.1 mg in patients >10 kg. | |
|
b Maximum daily dose: 7.5 mg/day. | |
|
<0.3 mg/L |
Increase dose by 0.03 mg/kgb |
|
0.3 to 0.49 mg/L |
Increase dose by 0.01 mg/kgb |
|
0.5 to 1 mg/L |
Keep same dosage |
|
1.01 to 1.2 mg/L |
Decrease dose by 0.01 mg/kg |
|
>1.2 mg/L |
Decrease dose by 0.03 mg/kg |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Children and Adolescents weighing ≥10 kg: SUBQ:
Mild and moderate impairment: Use not recommended; no data to support safe and effective use exist in pediatric patients. In adults, anticoagulant effects may be prolonged in patients with kidney impairment.
Severe impairment: Use is contraindicated.
Children and Adolescents weighing ≥10 kg:
Mild, moderate, and severe impairment: Use not recommended; no data to support safe and effective use exist in pediatric patients.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Hematologic & oncologic: Anemia (2% to 20%)
1% to 10%:
Cardiovascular: Hypotension (≤4%)
Dermatologic: Skin blister (3%)
Endocrine & metabolic: Hypokalemia (4%)
Hematologic & oncologic: Hematoma (2% to 3%), hemorrhage (≤3%; including major hemorrhage), postoperative hemorrhage (2%), purpuric disease (4%), thrombocytopenia (≤3%; severe: <1%)
Hepatic: Increased serum alanine aminotransferase (1% to 3%), increased serum aspartate aminotransferase (≤2%)
Nervous system: Confusion (1% to 3%), dizziness (≤4%), insomnia (5%)
Respiratory: Epistaxis (1%)
<1%: Nervous system: Intracranial hemorrhage
Frequency not defined: Local: Injection-site reaction (including bleeding at injection site, injection-site pruritus, rash at injection site)
Postmarketing:
Cardiovascular: Thrombosis (associated with fondaparinux-induced thrombocytopenia)
Hematologic & oncologic: Elevated aPTT associated with bleeding
Hypersensitivity: Anaphylaxis, angioedema, nonimmune anaphylaxis
Nervous system: Epidural intracranial hemorrhage, spinal hematoma
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 (venous thromboembolism prophylaxis in adults); active major bleeding; bacterial endocarditis; thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of fondaparinux.
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: congenital or acquired bleeding disorders; active ulcerative and angiodysplastic GI disease; uncontrolled arterial hypertension; diabetic retinopathy; hemorrhagic stroke; use shortly after brain, spinal, or ophthalmology surgery; adults with renal impairment; and/or adults weighing <50 kg. Pediatric patients may be at increased risk of bleeding with conditions such as systemic lupus erythematosus, Wilms tumor, antiphospholipid syndrome, antithrombin III deficiency, Factor V Leiden, malignancy, pancytopenia, indwelling chest tubes, thoracotomy, invasive infections, hypertensive encephalopathy, intestinal lymphangiectasia, and von Willebrand disease. 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). 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 adults with renal impairment. Use with caution in patients with CrCl 30 to 50 mL/minute (may cause prolonged anticoagulation); discontinue immediately if severe renal impairment develops.
Special populations:
• Adults <50 kg: In adults weighing <50 kg, clearance of fondaparinux is reduced by 30% and the risk of bleeding is increased.
• Older adult: Use with caution in older adults; increased risk of bleeding in patients >75 years of age.
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.
• Percutaneous coronary intervention: The administration of fondaparinux as the sole anticoagulant is not recommended during percutaneous coronary intervention (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 [Lawton 2022]).
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)
Yes
Solution (Arixtra Subcutaneous)
2.5 mg/0.5 mL (per 0.5 mL): $66.74
5 mg/0.4 mL (per 0.4 mL): $157.05
7.5 mg/0.6 mL (per 0.6 mL): $157.05
10 mg/0.8 mL (per 0.8 mL): $157.05
Solution (Fondaparinux Sodium Subcutaneous)
2.5 mg/0.5 mL (per 0.5 mL): $14.70 - $57.70
5 mg/0.4 mL (per 0.4 mL): $42.12 - $135.80
7.5 mg/0.6 mL (per 0.6 mL): $35.10 - $135.80
10 mg/0.8 mL (per 0.8 mL): $42.12 - $135.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous, as sodium:
Arixtra: 2.5 mg/0.5 mL (0.5 mL); 7.5 mg/0.6 mL (0.6 mL)
Generic: 2.5 mg/0.5 mL (0.5 mL); 7.5 mg/0.6 mL (0.6 mL)
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.
Note: After proper training, prefilled syringes may be used for self-administration or administration by a caregiver.
Parenteral: SUBQ: For SUBQ administration; do not administer IM. Administer in fatty tissue and alternate injection sites between the left and right anterolateral or left and right posterolateral abdominal wall.
Prefilled syringe: Do not expel air bubble from commercial prefilled syringe prior to injection.
Missed dose: Administer missed dose as soon as possible; do not administer two doses at the same time.
Venous thromboembolism prophylaxis in surgical patients: Prophylaxis of venous thromboembolism in adults 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).
Venous thromboembolism treatment: Treatment of acute deep vein thrombosis or acute pulmonary embolism in adults; treatment of venous thromboembolism in pediatric patients ≥1 year of age and weighing ≥10 kg.
Acute coronary syndrome; Heparin-induced thrombocytopenia treatment; Superficial vein thrombosis, acute symptomatic; Venous thromboembolism prophylaxis in medical patients with acute illness; Venous thromboembolism prophylaxis in patients undergoing major surgery for cancer
Arixtra may be confused with Aristada, Arista AH (hemostatic device)
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (factor Xa inhibitor) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acalabrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Aducanumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with aducanumab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Alemtuzumab: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Alteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Anacaulase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Anagrelide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Antidepressants with Antiplatelet Effects: May increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): May increase anticoagulant effects of Fondaparinux. Management: Discontinue antiplatelet agents, such as P2Y12 inhibitors, prior to fondaparinux therapy, if possible. If co-administration is required use caution and monitor for bleeding. Risk D: Consider Therapy Modification
Apixaban: May increase anticoagulant effects 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. Risk X: Avoid
Aspirin: May increase anticoagulant effects of Fondaparinux. Management: Discontinue aspirin prior to fondaparinux therapy, if possible. If co-administration is required use caution and monitor for bleeding. Risk D: Consider Therapy Modification
Bromperidol: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
Caplacizumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider Therapy Modification
Certoparin: Fondaparinux may increase anticoagulant effects of Certoparin. Risk C: Monitor
Chloroprocaine (Systemic): Anticoagulants may increase adverse/toxic effects of Chloroprocaine (Systemic). Risk C: Monitor
Cilostazol: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Collagenase (Systemic): Anticoagulants may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor
Dabigatran Etexilate: May increase anticoagulant effects 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. Risk X: Avoid
Dasatinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Deferasirox: Anticoagulants may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Defibrotide: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Deoxycholic Acid: Anticoagulants may increase adverse/toxic effects of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor
Desirudin: Anticoagulants may increase anticoagulant effects of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider Therapy Modification
Donanemab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with donanemab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Edoxaban: May increase anticoagulant effects 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. Risk X: Avoid
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may decrease therapeutic effects of Factor X (Human). Risk C: Monitor
Glycoprotein IIb/IIIa Inhibitors: May increase anticoagulant effects of Fondaparinux. Management: Discontinue antiplatelet agents, such as glycoprotein IIb/IIIa inhibitors, prior to fondaparinux therapy, if possible. If co-administration is required, use caution and monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Hemin: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase adverse/toxic effects of Anticoagulants. Bleeding may occur. Risk C: Monitor
Ibritumomab Tiuxetan: Anticoagulants may increase adverse/toxic effects of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor
Ibrutinib: Anticoagulants may increase adverse/toxic effects of Ibrutinib. Specifically, the risks of bleeding and hemorrhage may be increased. Risk C: Monitor
Icosapent Ethyl: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Inotersen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Kanamycin: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Lecanemab: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Management: Avoid use of lecanemab in patients who are being treated with an anticoagulant when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Limaprost: May increase adverse/toxic effects of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor
Lipid Emulsion (Fish Oil Based): May increase anticoagulant effects of Anticoagulants. Lipid Emulsion (Fish Oil Based) may decrease anticoagulant effects of Anticoagulants. Risk C: Monitor
Mesoglycan: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
MiFEPRIStone: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid
Miscellaneous Antiplatelets: May increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Nintedanib: Anticoagulants may increase adverse/toxic effects of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May increase anticoagulant effects of Fondaparinux. Management: Discontinue nonselective nonsteroidal anti-inflammatory agents prior to the initiation of fondaparinux, if possible. If coadministration is required, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Obinutuzumab: Anticoagulants may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Management: Consider avoiding coadministration of obinutuzumab and anticoagulants, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omacetaxine: Anticoagulants may increase adverse/toxic effects 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. Risk X: Avoid
Omega-3 Fatty Acids: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Ozagrel: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of ozagrel and anticoagulants if possible. If coadministration is required, use caution, monitor patients closely for signs and symptoms of bleeding, and consider ozagrel or anticoagulant dose reductions. Risk D: Consider Therapy Modification
Pentosan Polysulfate Sodium: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Pirtobrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Protein C Concentrate (Human): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Reteplase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Rivaroxaban: Anticoagulants may increase anticoagulant effects 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. Risk X: Avoid
Salicylates: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Streptokinase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Sugammadex: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Sulodexide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Tenecteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Tibolone: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Tipranavir: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Urokinase: May increase anticoagulant effects of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Vitamin E (Systemic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vitamin K Antagonists: Anticoagulants may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vorapaxar: May increase adverse/toxic effects of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid
Zanubrutinib: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
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).
It is not known if fondaparinux is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. The use of alternative anticoagulants is preferred (Guyatt 2012).
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.
Note: Routine coagulation monitoring is not recommended (ACCP [Garcia 2012]); a therapeutic anti-Xa activity range has not been established. The following fondaparinux concentrations have been reported by the manufacturer; however, dose adjustments based on these concentrations have not been established.
Thromboprophylaxis dosing (eg, 2.5 mg once daily): Peak steady state plasma concentration at 3 hours post dose: ~0.39 to 0.5 mg/L
Therapeutic dosing (eg, 7.5 mg once daily in patients weighing 50 to 100 kg): Peak steady state plasma concentration at 3 hours post dose: 1.2 to 1.26 mg/L
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.
Absorption: SubQ: Rapid and complete
Distribution: Vd: 7 to 11 L; mainly in blood
Protein binding: ≥94% to antithrombin III
Bioavailability: SubQ: 100%
Half-life elimination: 17 to 21 hours; prolonged with renal impairment and in the elderly
Time to peak: SubQ: ~2 to 3 hours
Excretion: Urine (up to 77%, unchanged drug)
Altered kidney function: Elimination is prolonged.
Hepatic function impairment: In patients with moderate hepatic impairment (Child-Pugh class B), Cmax and AUC were decreased by 22% and 39%, respectively.
Older adult: Elimination is prolonged in patients older than 75 years.
Body weight: Total clearance is decreased approximately 30% in patients weighing less than 50 kg.
