Arixtra 10mg/0.8ml

Interactions with herbal products have not been established.

Interactions with food have not been established.

In clinical studies performed with ARIXTRA (fondaparinux sodium), the concomitant use of oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam) and digoxin did not interact with the pharmacokinetics/pharmacodynamics of ARIXTRA. In addition, ARIXTRA neither influenced the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam and digoxin, nor the pharmacokinetics of digoxin at steady state.

Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of ARIXTRA therapy unless indicated for the management of the underlying condition, such as vitamin K antagonists for the treatment of venous thromboembolism (VTE). If co-administration is necessary, close monitoring may be appropriate.

Since fondaparinux does not inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4) in vitro, ARIXTRA is not expected to interact with other drugs metabolized in vivo via these isoenzymes.

ARIXTRA does not bind significantly to plasma proteins other than ATIII, therefore, drug interactions by protein binding displacement are not expected.

See Warnings and Precautions, Monitoring, Laboratory and Coagulation Tests.

The risk of hemorrhage increases with increasing renal insufficiency. ARIXTRA should be used with caution in patients with moderate renal insufficiency (creatinine clearance 30-50 mL/min) (see Action and Clinical Pharmacology, Renal Insufficiency). In severe renal impairment, the use of ARIXTRA should be avoided or, if the physician determines that the benefit outweighs the risk, ARIXTRA should only be used with caution.

Renal function should be assessed periodically in patients receiving the drug. For prophylactic use following orthopedic surgery, ARIXTRA should be discontinued immediately in patients who develop severe renal insufficiency or labile renal function while on therapy. After discontinuation of ARIXTRA, its anticoagulant effects may persist for 2-4 days in patients with normal renal function (i.e., at least 3-5 half-lives). The anticoagulant effects of ARIXTRA may persist even longer in patients with renal insufficiency.

For patients of body weight <50 kg, ARIXTRA should be used with caution (see Warnings and Precautions, Low Body Weight).

Use with caution in patients with hepatic insufficiency (see also Warnings and Precautions).

The recommended dose of ARIXTRA is 2.5 mg once daily administered post-operatively by subcutaneous injection after hemostasis has been established.

The initial dose should be given 6 to 8 hours after surgery. Administration before 6 hours after abdominal surgery has been associated with an increased risk of major bleeding. The timing of the first dose of ARIXTRA following surgery requires strict adherence (see Warnings and Precautions, Hemorrhage, and Peri-operative Considerations; Action and Clinical Pharmacology).

The usual duration of administration is 5 to 9 days, and up to 10 days of ARIXTRA injection has been administered.

Use with caution in elderly patients (see Warnings and Precautions, Geriatrics (>65 years of age), and Adverse Reactions, Geriatrics).

The recommended dose of ARIXTRA is 2.5 mg once daily, administered by subcutaneous injection. Treatment should be initiated as soon as possible following diagnosis and may be continued for up to 8 days or until hospital discharge.

If a patient is to undergo percutaneous coronary intervention (PCI) while being treated with ARIXTRA, an effective anti-thrombin regimen such as unfractionated heparin (UFH) should be administered as an adjunct to PCI, as per standard practice, taking into account the patient’s potential risk of bleeding, including the time since the last dose of ARIXTRA (see Warnings and Precautions, Risk of catheter thrombosis during PCI, and Hemorrhage).

The timing of restarting subcutaneous ARIXTRA after sheath removal should be based on clinical judgment. In the UA/NSTEMI clinical trials treatment with ARIXTRA was restarted no earlier than 2 hours after sheath removal.

In patients who are to undergo coronary artery bypass graft (CABG) surgery, ARIXTRA where possible, should not be given during the 24 hours before surgery and may be restarted 48 hours post-operatively.

For STEMI patients treated with ARIXTRA, the initial dose is to be administered intravenously. Administration should be through an existing intravenous line either directly or using a small volume (25 mL or 50 mL) 0.9% saline minibag as the first dose in the treatment of STEMI.

To avoid the loss of medicinal product when using the pre-filled syringe, do not expel the air bubble from the syringe before the injection. The intravenous tubing should be well flushed with saline after the administration of ARIXTRA injection to ensure that all of the medicinal product is administered. If administered via a minibag, the infusion should be given over 1 to 2 minutes.

If ARIXTRA is added to a 0.9% saline minibag it should be infused immediately, but can be stored between 15-30°C for up to 24 hours. Minibags are typically composed of a variety of polymers including PVC, polyethylene, polypropylene, or styrene-ethylene-butadiene, individually or in combination.

In the absence of compatibility studies, ARIXTRA must not be mixed with other medicinal products.

The recommended dose of ARIXTRA is 5 mg (body weight <50 kg), 7.5 mg (body weight 50-100 kg) or 10 mg (body weight >100 kg) by subcutaneous injection once daily.

Concomitant oral anticoagulation treatment should be initiated as soon as possible, usually within 72 hours. ARIXTRA injection treatment should be continued for at least 5 days and until a therapeutic oral anticoagulant effect is established (INR 2.0 to 3.0).

The average duration of administration is 7 days. In controlled clinical trials administration of ARIXTRA injection for up to 26 days to a small number of patients has been well tolerated.

Administration is by subcutaneous injection only. Do not inject ARIXTRA intramuscularly.

To avoid the loss of medicinal product when using the pre-filled syringe do not expel the air bubble from the syringe before the injection. For step-by-step instructions for use, please see Information for the Patient.

The recommended dose of ARIXTRA is 2.5 mg once daily. The first dose of ARIXTRA is administered intravenously and subsequent doses are administered by subcutaneous injection. Treatment should be initiated as soon as possible following diagnosis and continued for up to 8 days or until hospital discharge.

ARIXTRA should not be used if primary PCI is the planned reperfusion therapy (see Indications and Clinical Use, and Warnings and Precautions, Risk of catheter thrombosis during PCI). ARIXTRA is indicated for use in patients who are managed with thrombolytics or who initially are to receive no form of reperfusion therapy.

If a patient is to undergo subsequent PCI while being treated with ARIXTRA, an effective anti-thrombin regimen such as unfractionated heparin (UFH) should be administered as an adjunct to PCI as per standard practice, taking into account the patient’s potential risk of bleeding, including the time since the last dose of ARIXTRA (see Warnings and Precautions, Risk of catheter thrombosis during PCI, and Hemorrhage).

There are limited data on the use of UFH during non-primary PCI in patients treated with fondaparinux. In those patients with STEMI who underwent non-primary PCI in OASIS-6 less than 6 hours after the last dose of fondaparinux, the median dose of UFH was 5000 IU and the incidence of major bleeding was 4.1% (2/49). In those patients who underwent non-primary PCI 6-24 hours after the last dose of fondaparinux, the median dose of UFH was 8000 IU and the incidence of major bleeding was 2% (2/98).

The timing of restarting subcutaneous fondaparinux after sheath removal should be based on clinical judgment. In the STEMI clinical trials treatment with fondaparinux was restarted no earlier than 3 hours after sheath removal.

In patients who are to undergo coronary artery bypass graft (CABG) surgery, fondaparinux where possible, should not be given during the 24 hours before surgery and may be restarted 48 hours post-operatively.

The recommended dose of ARIXTRA (fondaparinux sodium) is 2.5 mg once daily administered post-operatively by subcutaneous injection.

After hemostasis has been established, the initial dose should be given no earlier than 6 hours after surgical closure. In clinical studies, 99% of the patients had received the initial dose of ARIXTRA by 18 hours after surgical closure. Administration before 6 hours after orthopedic surgery has been associated with an increased risk of major bleeding. The timing of the first dose of ARIXTRA following surgery requires strict adherence (see Warning and Precautions, Hemorrhage, and Peri-operative Considerations; Action and Clinical Pharmacology).

The usual duration of prophylactic therapy with ARIXTRA is 7±2 days. Treatment should be continued for as long as the risk of VTE persists. In patients for whom extended prophylaxis is indicated, administration of ARIXTRA in or out of the hospital up to an additional 24 days is recommended. In clinical trials of extended prophylaxis, a total of 32 days (peri-operative and extended prophylaxis) has been tolerated.

The following adverse reactions have been identified during post-approval use of ARIXTRA.

Rare spontaneous reports of elevated aPTT have been received at the 2.5 mg dose. A causal association between treatment with fondaparinux and the occurrence of elevated aPTT has not been established.

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

The data described below reflect experience in over 25 000 patients randomized to ARIXTRA (fondaparinux sodium) Injection in controlled trials of hip fracture, hip replacement, major knee, or abdominal surgeries, treatment of DVT and PE, and the management of UA/NSTEMI and STEMI. Patients received ARIXTRA primarily in two large peri-operative dose-response trials (n=989), four active-controlled peri-operative VTE prophylaxis trials with enoxaparin sodium (n=3616), an extended VTE prophylaxis trial (n=327), an active-controlled VTE prophylaxis trial with dalteparin sodium (n=1425) in abdominal surgery, a dose-response trial (n=111) and an active-controlled trial with enoxaparin sodium in DVT treatment (n=1091), an active-controlled trial with heparin in PE treatment (n=1092), OASIS 5, an active-controlled trial with enoxaparin in the treatment of UA/NSTEMI (n=9979), and OASIS 6, an active and placebo-controlled trial with standard of care in the treatment of STEMI (n=5954).

In the DVT and PE treatment clinical trials asymptomatic increases in AST and ALT levels >3 times the upper limit of normal of the laboratory reference range have been reported in 0.7% and 1.3% of patients, respectively, during the ARIXTRA injection treatment regimen.

In comparison, these increases have been reported in 4.8% and 12.3% of patients, respectively, in the DVT treatment trial during treatment with enoxaparin sodium 1 mg/kg every 12 hours, and in 2.9% and 8.7% of patients, respectively, in the PE treatment trial during treatment with aPTT adjusted heparin.

Major bleeding from the first active ARIXTRA dose decreased by 26% if the first dose was given 6 hours after surgical closure: major bleeding with ARIXTRA started <6 hours after surgical closure was 2.6% (n=1337) versus major bleeding with ARIXTRA started 6 hours after surgical closure which was 1.9% (n=2230).

Skin rash and allergic reactions are rare but occur with many antithrombotics. As with any subcutaneous injection, mild local irritation (injection site bleeding, rash and pruritus) may occur following subcutaneous injection of ARIXTRA.

Over 2300 STEMI patients, 65 years or older, received treatment with ARIXTRA. In the STEMI clinical trials with patients receiving ARIXTRA, the risk of severe hemhorrage was: 0.6% (22/3565) in patients <65 years, 1.5% (23/1518) in those 65-74 years, and 2.2% (19/871) in those ≥75 years.

As with any antithrombotic treatment, hemorrhagic manifestations can occur. The incidence of major hemorrhagic complications during ARIXTRA treatment has been low and generally did not differ from that observed with other antithrombotics. In clinical trials or in post-marketing experience, rare cases of intracranial/intracerebral or retroperitoneal bleedings have been reported.

Transient elevation of liver transaminases (AST and ALT) to >3 times the upper limit of laboratory range have been observed with the peri-operative prophylactic use of ARIXTRA as have been seen with other antithrombotics such as low molecular weight heparins. Such elevations are fully reversible and are rarely associated with increases in bilirubin. Transient transaminase increases >3 times upper limit of laboratory range during the extended prophylaxis clinical trial were as follows: ALT–4 /272 (1.5%) ARIXTRA vs. 2 /274 (0.7%) placebo; AST–2 /268 (0.7%) ARIXTRA vs. 1/ 271 (0.4%) placebo. However, these increases were reversible and there was no significant difference in the change in the hepatic enzymes between the two treatment groups from the baseline post-randomization period to the last value on double blind treatment.

In those patients who underwent non-primary PCI <6 hours after the last dose of fondaparinux, the median dose of UFH used was 5000 IU and the incidence of major bleeding was 4.1% (2/49). In those patients who underwent non-primary PCI 6-24 hours after the last dose of fondaparinux, the median dose of UFH was 8000 IU and the incidence of major bleeding was 2% (2/98).

The relative effects of ARIXTRA compared to control on severe hemorrhage or any hemorrhage up to Day 9 by clopidogrel use were consistent with that observed for the overall population.

See Warnings and Precautions, Hematologic.

Clinical trials have shown an increased risk of guiding catheter thrombosis in patients treated solely with ARIXTRA for anticoagulation during percutaneous coronary intervention (PCI) compared to control (see Warnings and Precautions, Cardiovascular). The incidence of catheter thrombus in STEMI patients undergoing primary PCI were 1.18% (22/1862) for ARIXTRA, when ARIXTRA was used as the sole adjunctive therapy, compared to 0% for UFH (0/1853). In STEMI patients treated with ARIXTRA undergoing non-primary PCI (234 patients, 238 procedures) who received UFH as an adjunct to the procedure, no cases of guiding catheter thrombus occurred.

In STEMI patients undergoing primary percutaneous coronary intervention (PCI) for reperfusion, the use of ARIXTRA prior to and during PCI is not recommended (see Adverse Reactions, Risk of catheter thrombosis during PCI, and Dosage and Administration).

ARIXTRA should be used with caution in elderly patients due to the risk of hemorrhage.

The safety and effectiveness of ARIXTRA in children has not been established.

Each pre-filled 0.5 mL single use syringe, affixed with a 27 gauge x ½ inch needle with a blue plunger within a built-in automatic needle protection, contains: fondaparinux sodium 2.5 mg. Packages of 10.

Each 0.6 mL single use pre-filled syringe, affixed with a 27-gauge x ½ inch needle with a magenta plunger within a built-in automatic needle protection, contains: fondaparinux sodium 7.5 mg. Packages of 10.

As with all parenteral drug products, syringes should be inspected visually for clarity, particulate matter, precipitate, discolouration and leakage prior to administration. Solutions showing haziness, particulate matter, precipitate, discolouration or leakage should not be used.

The plasma clearance of fondaparinux decreases with the severity of renal impairment, and is associated with an increased risk of hemorrhage (see Action and Clinical Pharmacology, Renal Insufficiency). This has also been observed with all low molecular weight heparins (LMWH).

There have been cases of intra-spinal hematomas with the concurrent use of antithrombotics (i.e. low molecular weight heparins) and spinal/epidural anaesthesia resulting in long-term or permanent paralysis. The risk of these events may be higher with the use of post-operative indwelling epidural catheters or by the concomitant use of drugs affecting hemostasis: nonsteroidal anti-inflammatory drugs (NSAIDS), platelet inhibitors, or other drugs affecting coagulation. The risk also appears to be increased by traumatic or repeated epidural or spinal procedure. ARIXTRA should only be used concurrently with spinal/epidural anaesthesia when the therapeutic benefits to the patients outweigh the possible risks. Careful vigilance for neurological signs is recommended with rapid diagnosis and treatment, if signs occur.

For DVT and PE treatment, patients with body weight <50 kg a daily dose of 5 mg is recommended. In patients with body weight >100 kg a daily dose of 10 mg is recommended (see Dosage and Administration).

The safety and effectiveness of ARIXTRA in children under the age of 17 years has not been established.

There are very limited clinical data available on the use of ARIXTRA in pregnant women. Caution should be exercised when prescribing ARIXTRA to pregnant women. ARIXTRA should not be prescribed to pregnant women unless the potential benefit outweighs the risk. Animal studies do not indicate either direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or post-natal development.

In patients undergoing any percutaneous coronary intervention (PCI), the use of ARIXTRA as the sole anticoagulant during PCI is not recommended because of an increased risk of guiding catheter thrombosis. An effective anti-thrombin regimen such as unfractionated heparin (UFH) should be used as an adjunct to PCI, according to standard practice (see Dosage and Administration).

In STEMI patients undergoing primary PCI for reperfusion, the use of ARIXTRA prior to and during PCI is not recommended (see Adverse Reactions, Risk of Catheter Thrombosis During PCI, and Dosage and Administration).

Clinical trials have shown a low but increased risk of guiding catheter thrombosis in patients treated solely with ARIXTRA for anticoagulation during PCI compared to control. Incidences during PCI in UA/NSTEMI were 1.00% with ARIXTRA, 0.32% with enoxaparin alone, and 0.16% with enoxaparin with adjunctive UFH (see Adverse Reactions, Risk of Catheter Thrombosis During PCI). In patients with STEMI undergoing primary PCI, incidences were 1.18% with ARIXTRA and 0% with UFH. Use of ARIXTRA during primary PCI is not recommended.

It is to be expected that the risk of peri-procedural myocardial infarction (MI) may be increased in patients who develop guiding catheter thrombosis, irrespective of anticoagulant used (see Adverse Reactions, Risk of Catheter Thrombosis During PCI).

The pharmacokinetic properties of fondaparinux have not been studied in patients with hepatic insufficiency.

There is no evidence that fondaparinux is metabolized or eliminated hepatically. However, the use of ARIXTRA should be considered with caution because of an increased risk of bleeding due to a deficiency of coagulation factors in patients with severe hepatic insufficiency. Thus, in patients with severe hepatic insufficiency, ARIXTRA, like any anticoagulant, should be used only with care.

ARIXTRA should be used with caution in elderly patients because of increased risk of hemorrhage (see Adverse Reactions). Since fondaparinux sodium is substantially excreted by the kidney, risks associated with its use may be expected to be greater in patients with impaired renal function (see Adverse Reactions, and Dosage and Administration). Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function (see Warnings and Precautions, Renal).

Patients with body weight <50 kg are at increased risk of bleeding. ARIXTRA prophylactic therapy should be used only with caution in patients with body weight <50 kg undergoing orthopedic surgery.

ARIXTRA (fondaparinux sodium) must be administered only by the subcutaneous (SC) or intravenous (IV) route. ARIXTRA must not be administered intramuscularly.

ARIXTRA, like other antithrombotic drugs, should be used with caution in patients who have an increased risk of hemorrhage, such as those with congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease and recent intracranial hemorrhage or shortly after brain, spinal, or ophthalmological surgery.

Risk of hemorrhage is expected to increase with decreasing renal function (see Adverse Reactions). Appropriate caution should be exercised in patients with moderate to severe renal impairment (see Warnings and Precautions, Renal).

The timing of the first dose of ARIXTRA following surgery requires strict adherence. The first dose should be given no earlier than 6 hours following surgical closure, and only after hemostasis has been established. Administration before 6 hours has been associated with an increased risk of major bleeding (see Dosage and Administration). Patient groups at particular risk are those older than 75 years of age, body weight of less than 50 kg or renal impairment with creatinine clearance less than 50 mL/min.

Since the international standards of heparin or low molecular weight heparins (LMWH) are not appropriate calibrators, the activity of fondaparinux sodium is expressed in milligrams (mg) of the fondaparinux and cannot be compared with activities of heparin or LMWH.

At the 2.5 mg dose, ARIXTRA does not have a clinically relevant effect on routine coagulation tests such as activated partial thromboplastin time (aPTT), activated clotting time (ACT) or prothrombin time (PT)/International Normalized Ratio (INR) tests in plasma. When administered at the recommended prophylactic dose, routine coagulation tests such as PT and aPTT are relatively insensitive measures of ARIXTRA activity, and therefore unsuitable for monitoring. Although monitoring of ARIXTRA is generally not required, the anti-factor Xa assay is the preferred test to measure the anti-coagulant activity of ARIXTRA. Only fondaparinux can be used to calibrate the anti-Xa assay (see Action and Clinical Pharmacology, Mechanism of Action).

If during ARIXTRA therapy, unexpected changes in coagulation parameters or major bleeding occurs, ARIXTRA should be discontinued and a search for other causes such as concomitant medications that could interfere with coagulation, should be undertaken.

The needle guard of the pre-filled syringe contains dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.

Agents that may enhance the risk of hemorrhage, with the exception of vitamin K antagonists used concomitantly for treatment of VTE, should be discontinued prior to initiation of ARIXTRA therapy. If co-administration is necessary, close monitoring may be appropriate (see Drug Interactions).

Patients with body weight less than 50 kg may be at increased risk of bleeding due to reduced clearance of ARIXTRA. ARIXTRA should be used with caution in patients weighing <50 kg.

Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 50 000/mm³, ARIXTRA should be discontinued. ARIXTRA is contraindicated in patients with thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux.

Rare spontaneous reports of heparin-induced thrombocytopenia (HIT) in patients treated with fondaparinux have been received.

Although it is not known whether fondaparinux is excreted in human milk, it has been shown to be excreted in the milk of lactating rat dams. Because many drugs may be excreted in human milk, breast feeding is not recommended during treatment with ARIXTRA.

Fondaparinux elimination is prolonged in patients over 75 years old. In studies evaluating fondaparinux sodium 2.5 mg prophylaxis in hip fracture surgery or elective hip surgery, the total clearance of fondaparinux was approximately 25% lower in patients over 75 years old as compared to patients less than 65 years old. A similar pattern is observed in DVT and PE treatment patients.

Following a single intravenous dose of fondaparinux 4 mg in healthy elderly subjects, a mean C_max of 0.86 mg/L was observed at the first sampling timepoint of 5 minutes. Other pharmacokinetic parameters following intravenous administration were similar to those observed for subcutaneous administration.

In healthy adults, intravenously or subcutaneously administered fondaparinux distributes mainly in blood as evidenced by steady state and non-steady state apparent volume of distribution of 7 to 11 L.

In vitro fondaparinux is highly (at least 94% in the concentration range from 0.5 to 2 mg/L) and specifically bound to ATIII and does not bind significantly to other plasma proteins, including Platelet Factor 4 (PF4).

Following a single 4 mg i.v. bolus administration to normal healthy subjects, mean peak fondaparinux plasma concentration is approximately 0.81 mg/L at the first sampling time point of 5 minutes. After subcutaneous dosing, fondaparinux is completely and rapidly absorbed, with an absolute bioavailability of 100%. Following a single subcutaneous injection of 2.5 mg, peak plasma concentration (C_max=0.34 mg/L) is obtained 2 hours post-dosing. Plasma concentrations of half the mean C_max values are reached 25 minutes post-dosing.

Pharmacokinetics of fondaparinux are linear in the range of 2 to 8 mg by the subcutaneous route. At steady state, mean plasma concentrations 2 hours post dosing ranged between 0.32 and 0.47 mg/L in patients undergoing orthopedic surgeries receiving ARIXTRA 2.5 mg.

In patients with symptomatic deep vein thrombosis and pulmonary embolism undergoing treatment with fondaparinux sodium injection 5 mg (body weight <50 kg), 7.5 mg (body weight 50-100 kg) and 10 mg (body weight >100 kg) once daily, the body-weight-adjusted doses provide similar exposure across all body weight categories. The peak steady-state plasma concentration is, on average, 1.20-1.26 mg/L. In these patients, the minimum steady-state plasma concentration is 0.46-0.62 mg/L.

ARIXTRA (fondaparinux sodium) Injection is a synthetic and specific inhibitor of activated Factor X (Xa). As ARIXTRA has no animal-sourced components, there is no risk of animal contamination such as transmissable spongiform encephalitis (TSE).

The mechanism of action of ARIXTRA is the potentiation of antithrombin III (ATIII) which selectively inhibits Factor Xa. By selectively binding to ATIII, ARIXTRA potentiates approximately 300 times the neutralization of Factor Xa. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development.

ARIXTRA does not inactivate thrombin (activated Factor II) and has no effect on platelets. At the recommended dose, ARIXTRA does not affect fibrinolytic activity or bleeding time.

At equivalent antithrombotic concentrations, experimental bleeding models demonstrate that ARIXTRA induces less bleeding than unfractionated heparin.

ARIXTRA does not bind to Human Platelet Factor 4 (unlike heparin) and does not cross-react with sera from patients with heparin-induced thrombocytopenia. No thrombocytopenia with suspected immuno-allergic pathophysiology was documented in the overall clinical development program.

Anti-Xa Activity: The pharmacodynamics/pharmacokinetics of fondaparinux sodium are derived from fondaparinux plasma concentrations quantified via anti-Factor Xa activity. Only fondaparinux can be used to calibrate the anti-Xa assay. (The international standards of heparin or Low Molecular Weight Heparin [LMWH] are not appropriate for this use). As a result, the activity of fondaparinux sodium is expressed as milligram (mg) of the fondaparinux calibrator. The anti-Xa activity of the drug increases with increasing drug concentration, reaching maximum values in approximately 3 hours.

The elimination half life (T_1/2) is 17 to 21 hours in healthy subjects.

Up to 77% of a single subcutaneous dose of fondaparinux is excreted in urine as unchanged compound in 72 hours in healthy individuals up to 75 years of age.

Fondaparinux elimination is prolonged in patients with renal insufficiency since the major route of elimination is urinary excretion of unchanged drug. In patients undergoing prophylaxis following elective hip surgery or hip fracture surgery, the total clearance of fondaparinux is approximately 25% lower in patients with mild renal insufficiency (creatinine clearance 50 to 80 mL/min), approximately 40% lower in patients with moderate renal insufficiency (creatinine clearance 30 to 50 mL/min) and approximately 55% lower in patients with severe renal insufficiency (<30 mL/min) compared to patients with normal renal function. The associated terminal half-life values were 29 hours in moderate and 72 hours in patients with severe renal insufficiency. A similar pattern is observed in DVT and PE treatment patients (see Warnings and Precautions, Renal.)

Patients Weighing Less Than 50 kg: Total clearance of fondaparinux sodium is decreased by approximately 30% in patients weighing less than 50 kg (see Dosage and Administration).

There is no evidence that fondaparinux is metabolized since most of the administered dose is eliminated unchanged in urine.

The pharmacokinetics of fondaparinux have not been investigated in pediatric patients.