Fondaparinux (Arixtra) injection is a synthetic anticoagulant that inhibits Factor Xa. It has no effect on thrombin. It is used for the treatment and prophylaxis of patients with deep vein thrombosis and pulmonary embolism.

Fondaparinux (Arixtra) Uses:

• Acute deep vein thrombosis:

  • Used in the treatment of acute DVT in conjunction with warfarin.

• Acute pulmonary embolism:

  • Used in the treatment of acute PE in conjunction with warfarin.

• Venous thromboembolism prophylaxis in surgical patients:

  • Prophylaxis of VTE in patients undergoing surgery for hip replacement, knee replacement, hip fractured (including extended prophylaxis following hip fracture surgery), or abdominal surgery (in patients at risk for thromboembolic complications).

• Off Label Use of Fondaparinux in Adults:

  • Used in acute coronary syndrome (non-ST-elevation acute coronary syndrome [NSTE-ACS] or ST-elevation myocardial infarction [STEMI])
  • Used in acute symptomatic superficial vein thrombosis (5 cm or more than 5 cm in length) of the legs
  • Used in acute thrombosis (unrelated to heparin-induced thrombocytopenia [HIT]) (history of HIT);
  • Used in HIT treatment
  • Used in venous thromboembolism prophylaxis (history of HIT)
  • Used in venous thromboembolism prophylaxis in hospitalized cancer patients
  • Used in venous thromboembolism prophylaxis in hospitalized medical patients with acute illness
  • Used in venous thromboembolism prophylaxis in patients undergoing major surgery for cancer

Fondaparinux (Arixtra) Dose in Childrens

Note: PT and aPTT are insensitive measures of fondaparinux activity. If unexpected changes in coagulation parameters or major bleeding occur, discontinue fondaparinux.

Fondaparinux (Arixtra) Dose in the treatment of Acute DVT/PE: SubQ:

• <50 kg:

  • 5 mg once a day

• 50 to 100 kg:

  • 7.5 mg once a day

• >100 kg:

  • 10 mg once a day

• Usual duration:

  • 5 to 9 days (administered up to 26 days in clinical trials)

Fondaparinux (Arixtra) Dose in the treatment of acute coronary syndrome (off-label):

• NSTE-ACS:

  • SubQ: 2.5 mg once a day;
  • treat for the duration of hospitalization or until PCI performed.

• STEMI:

  • IV: 2.5 mg  one time;
  • subsequent doses (starting the following day):
    • SubQ: 2.5 mg once a day;
    • treat for the duration of the hospitalization, up to 8 days, or until revascularization.

Fondaparinux (Arixtra) Dose in the treatment of Acute symptomatic superficial vein thrombosis (≥5 cm in length) of the legs (off-label):

• SubQ: 2.5 mg once a day for the time period of 45 days.

Fondaparinux (Arixtra) Dose in the treatment of Acute thrombosis (unrelated to HIT) in patients with a past history of HIT (off-label): SubQ:

• <50 kg:

  • 5 mg once a day

• 50 to 100 kg:

  • 7.5 mg once a day

• >100 kg:

  • 10 mg once a day

Fondaparinux (Arixtra) Dose in the treatment of Heparin-induced thrombocytopenia (alternative agent) (off-label):

Note: For starting  therapy of acute HIT in selected hemodynamically stable patients: SubQ:

• <50 kg:

  • 5 mg once a day

• 50 to 100 kg:

  • 7.5 mg once a day

• >100 kg:

  • 10 mg once a day

• Duration:

  • Although not well defined, a total minimum duration of 4 weeks is typically used for patients without thrombosis;
  • Minimum duration of 3 months is used for patients who have HIT-associated thrombosis.
  • For patients without thrombosis, some experts consider anticoagulation until platelet count recovery, allowing potentially for a shorter time period.

Fondaparinux (Arixtra) Dose in the prophylaxis of Venous thromboembolism:

• Hospitalized medical patients with acute illness at moderate and high risk for VTE (including patients with active cancer or history of HIT [off label]):

  • SubQ: 2.5 mg once a day;
  • continue for the length of hospital stay or until the patient is fully ambulatory and the risk of VTE has diminished.

• Major surgery for cancer (off-label):

  • SubQ: 2.5 mg once in a day 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.

• Surgical patients:

  • SubQ:
    • ≥50 kg: 2.5 mg once in a day beginning after hemostasis has been established, no earlier than 6 to 8 hours postoperatively.
    • Note: Prophylactic use contraindicated in patients less than 50 kg.
  • Duration in non-orthopedic surgery:
    • Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days).
  • Duration in orthopedic surgery:
    • The 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 the higher end of the range (eg, ~30 days) for total hip arthroplasty.
    • For extended prophylaxis, may transition to an oral anticoagulant.

• 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.
  • 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.
  • 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.

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

Arixtra use in children:

Not recommended.

Fondaparinux (Arixtra) Pregnancy Risk Category: B

• According to case reports, the drug was detected in small quantities in the umbilical cord after multiple doses of pregnancy.
• Fondaparinux should not be used during pregnancy if a woman has severe allergic reactions to Heparin (including heparin-inducedthrombocytopenia) and cannot receive danaparoid.

Fondaparinux use during breastfeeding:

• Fondaparinux may be present in breast milk, but it is unknown.
• According to the manufacturer of the product, when deciding whether to continue or stop breastfeeding during therapy, it should consider the risks to infant exposure, the benefits to the infant and the benefits to the mother.
• It is preferable to use alternative anticoagulants.

Fondaparinux (Arixtra) Dose in Kidney Disease:

• CrCl >50 mL/minute:

  • The manufacturer's labeling doesn't provide any dosage adjustments.
  • Total clearance is reduced ~25 percent compared to patients with normal renal function.

• CrCl 30 to 50 mL/minute:

  • Use caution;
  • The total clearance ~40 percent lower compared to patients with normal renal function.
  • When used for thromboprophylaxis, the American College of Chest Physicians suggests a 50 percent reduction in dose or use of low-dose heparin instead of fondaparinux.

• CrCl <30 mL/minute:

  • Its use is contraindicated.

• Hemodialysis:

  • Dialyzable: Yes;
  • clearance increased by 20 percent.

Fondaparinux (Arixtra) Dose in Liver disease:

• Mild-to-moderate impairment (Child-Pugh class A and B):

  • No dosage adjustment required; monitor for signs of bleeding.

• Severe impairment (Child-Pugh class C):

  • The manufacturer's labeling doesn't provide any dosage adjustments(has not been studied).
  • Use with caution; monitor closely for signs of bleeding.

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

Common Side Effects of Fondaparinux (Arixtra):

• Hematologic & oncologic:

  • Anemia

Less Common Side Effects of Fondaparinux (Arixtra):

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Insomnia
  • Dizziness
  • Confusion

• Dermatologic:

  • Increased Wound Secretion
  • Skin Blister

• Endocrine & Metabolic:

  • Hypokalemia

• Hematologic & Oncologic:

  • Purpura
  • Thrombocytopenia
  • Hematoma
  • Minor Hemorrhage
  • Major Hemorrhage
  • Postoperative Hemorrhage

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Infection:

  • Postoperative Wound Infection

• Respiratory:

  • Epistaxis

Contraindication to Fondaparinux (Arixtra):

• Serious hypersensitivity (eg, anaphylactoid/anaphylactic, angioedema reactions) to fondaparinux or any component of the formulation;
• severe renal impairment (CrCl lower than 30 mL/minute);
• Body weight below 50 kg (prophylaxis);
• active major bleeding;
• bacterial endocarditis;
• Thrombocytopenia in association with an in vitro positive test for antiplatelet antibodies in the presence fondaparinux

Warnings and precautions

• Bleeding

  • Pay attention to bleeding symptoms and signs.
  • Patients at greater risk of bleeding are those with higher blood pressure.
  • Risk factors include:
    • bacterial endocarditis;
    • Congenital and acquired bleeding disorders
    • Uncontrolled arterial hypertension
    • Hemorrhagic stroke
    • Active ulcerative and angiodysplastic gastro-intestinal disease
    • Recent intracranial hemorhage
    • Use within a few hours of spinal, brain, or ophthalmology surgeries;
    • Patients who are being treated with platelet inhibitors concurrently;
    • thrombocytopenia or platelet defects;
    • Renal impairment
    • Diabetic retinopathy and/or
    • Patients less than 50kg
  • If the starting dose is given earlier than advised (initiation recommended for 6-8 hours after surgery), there may be a greater risk of major bleeding.
  • If you are treating an underlying condition, such as VTE or vitamin K antagonists, do not use any agents that increase the risk of hemorhage.
  • Fondaparinux activity can be measured by aPTT and PT.
  • Fondaparinux should be discontinued if there are any unexpected changes in coagulation or major bleeding. (Postmarketing data has reported elevated aPTTs associated with bleeding events).

• Thrombocytopenia:

  • It has occurred in patients who have had thrombocytopenia due to administration.
  • Patients with thrombocytopenia and a positive in vitro antiplatelet antibody test in the presence fondaparinux are advised not to use it.
  • If platelets fall below 100,000/mm3, monitor patients carefully and stop the therapy.

• Hepatic impairment

  • Patients with hepatic impairment may have higher bleeding chances.
  • It is important to use it with caution.

• Renal impairment

  • Patients with impaired renal function may be at greater risk of bleeding.
  • Patients with CrCl 30-50 mL/minute should be cautious as it can cause prolonged anticoagulation.
  • Patients with CrCl lower than 30 mL/minute are contraindicated
  • Monitor your renal function periodically;
  • discontinue immediately if severe renal impairment develops.

Fondaparinux: Drug Interaction

Monitoring parameters:

• Periodically monitor platelet count, serum creatinine, CBC, and occult blood testing of stools.
• Anti-Xa activity can be measured if the assay is specifically calibrated for fondaparinux.
• In patients undergoing neuraxial procedures, consider for signs/symptoms of neurologic impairment.

How to administer Fondaparinux (Arixtra)?

SubQ:

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

IV:

• For STEMI patients (off-label use), may administer the starting dose as an 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:

• 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:

• calculate specific dose for IV UFH infusion depended on indication;
• Discontinue fondaparinux;
• omit heparin bolus/loading dose

For subQ fondaparinux dosed every 24 hours:

• Start IV UFH infusion 22 to 23 hours after the last dose of fondaparinux

Mechanism of action of Fondaparinux (Arixtra):

• Fondaparinux, a synthetic pentasaccharide, causes an antithrombin-mediated selective inhibition factor Xa.
• The blood coagulation cascade is disrupted by neutralization of factor Xa.
• It also inhibits thrombin development and thrombin formation.

Absorption: SubQ:

• Rapid and complete

Distribution:

• mainly in blood

Protein binding:

• ≥94 percent  to antithrombin III

Bioavailability: SubQ:

• 100 percent

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 percent, unchanged drug)

International Brands of Fondaparinux (Arixtra):

• Arixtra
• Quixidar

Fondaparinux Brand Names in Pakistan: