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.
Note: Fondaparinux may be used in patients with acute or remote heparin-induced thrombocytopenia (HIT) (ACCP [Linkins 2012]; Warkentin 2011a).
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).
Deep vein thrombosis and/or pulmonary embolism treatment:
Note: 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: 3 months (provided the provoking risk factor is no longer present) (ACCP [Stevens 2021]).
Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of venous thromboembolism (VTE) recurrence and bleeding (ACCP [Stevens 2021]; ISTH [Baglin 2012]).
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals (ACCP [Stevens 2021]).
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: Not well established.
Heparin-induced thrombocytopenia without thrombosis: Typically, 4 weeks to 3 months (ACCP [Linkins 2012]). Some experts allow for discontinuation of anticoagulation after platelet count recovery, potentially resulting in a shorter duration (ASH [Cuker 2018]).
Heparin-induced thrombocytopenia with thrombosis: Typically, 3 to 6 months (ACCP [Linkins 2012]; ASH [Cuker 2018]).
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 (ACCP [Stevens 2021]; Decousus 2010).
Venous thromboembolism prophylaxis:
Note: Prophylactic use contraindicated in patients <50 kg. 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 2020]; 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 2020]).
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) (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. 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 2022).
Transitioning from warfarin to fondaparinux: Discontinue warfarin and initiate fondaparinux as soon as INR becomes subtherapeutic (Bauer 2022).
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 (Stacy 2018); total clearance reduced ~40% compared to patients with CrCl >80 mL/minute. Some experts would consider switching to an alternative anticoagulant (Bauer 2018).
When used for thromboprophylaxis, some experts recommend a 50% dose reduction or use of low-dose heparin instead of fondaparinux (ACCP [Garcia 2012]). Pharmacokinetic simulations and cohort studies suggest a 40% dose reduction (1.5 mg daily) (Mismetti 2012; Turpie 2009; Zufferey 2017).
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 (Mismetti 2012; Turpie 2009; Zufferey 2017).
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 (Kalicki 2007; Sombolos 2008; Speeckaert 2013).
Peritoneal dialysis: SubQ: Avoid use. Unlikely to be substantially cleared by peritoneal dialysis (expert opinion).
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.
(For additional information see "Fondaparinux: Pediatric drug information")
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 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 |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, dosage adjustments are suggested in mild and moderate renal impairment and fondaparinux is contraindicated in severe renal impairment.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, use with caution in severe hepatic impairment and monitor closely for signs and symptoms of bleeding.
Refer to adult dosing.
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
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); 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); 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.
Parenteral: SubQ: For SubQ administration; do not administer IM. In adults, it is recommended to alternate between the left or right anterolateral and left or right posterolateral abdominal wall. Do not expel air bubble from commercial prefilled syringe prior injection.
Deep vein thrombosis: Treatment of acute deep vein thrombosis.
Pulmonary embolism: Treatment of acute pulmonary embolism.
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).
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 drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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)
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
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.
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.
None known.
Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk X: Avoid combination
Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: 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. Risk X: Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Desirudin: Anticoagulants may enhance the anticoagulant effect 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
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. Risk X: Avoid combination
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Risk C: Monitor therapy
Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: 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. Risk X: Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
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. Risk C: 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. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: Monitor therapy
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination
Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
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)
Renal function impairment: 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.
Geriatric: Elimination is prolonged in patients older than 75 years.
Body weight: Total clearance is decreased approximately 30% in patients weighing less than 50 kg.
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): $29.38 - $57.70
5 mg/0.4 mL (per 0.4 mL): $69.13 - $135.80
7.5 mg/0.6 mL (per 0.6 mL): $69.13 - $135.80
10 mg/0.8 mL (per 0.8 mL): $69.13 - $135.80
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