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ARIXTRA (fondaparinux sodium) Solution for subcutaneous injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ARIXTRA safely and effectively. See full prescribing information for ARIXTRA.
ARIXTRA (fondaparinux sodium) Solution for subcutaneous injection
Initial U.S. Approval: 2001
WARNING: SPINAL/EPIDURAL HEMATOMAS
See full prescribing information for complete boxed warning.
Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH), heparinoids, or fondaparinux sodium 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:
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use of indwelling epidural catheters
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concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants
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a history of traumatic or repeated epidural or spinal puncture
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a history of spinal deformity or spinal surgery
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. [See Warnings and Precautions (5.5) and Drug Interactions (7).]
RECENT MAJOR CHANGES
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Boxed Warning |
07/2014 |
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Contraindications (4) |
09/2013 |
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Warnings and Precautions (5.5) |
07/2014 |
INDICATIONS AND USAGE
ARIXTRA is a Factor Xa inhibitor (anticoagulant) indicated for:
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Prophylaxis of deep vein thrombosis (DVT) in patients undergoing hip fracture surgery (including extended prophylaxis), hip replacement surgery, knee replacement surgery, or abdominal surgery. (1.1)
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Treatment of DVT or acute pulmonary embolism (PE) when administered in conjunction with warfarin. (1.2, 1.3)
DOSAGE AND ADMINISTRATION
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Prophylaxis of deep vein thrombosis: ARIXTRA 2.5 mg subcutaneously once daily after hemostasis has been established. The initial dose should be given no earlier than 6 to 8 hours after surgery and continued for 5 to 9 days. For patients undergoing hip fracture surgery, extended prophylaxis up to 24 additional days is recommended. (2.1, 2.2)
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Treatment of deep vein thrombosis and pulmonary embolism: ARIXTRA 5 mg (body weight <50 kg), 7.5 mg (50 to 100 kg), or 10 mg (>100 kg) subcutaneously once daily. Treatment should continue for at least 5 days until INR 2 to 3 achieved with warfarin sodium. (2.3)
Do not use as intramuscular injection. For subcutaneous use, do not mix with other injections or infusions.
DOSAGE FORMS AND STRENGTHS
Single-dose, prefilled syringes containing 2.5 mg, 5 mg, 7.5 mg, or 10 mg of fondaparinux. (3)
CONTRAINDICATIONS
ARIXTRA is contraindicated in the following conditions: (4)
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Severe renal impairment (creatinine clearance <30 mL/min) in prophylaxis or treatment of venous thromboembolism.
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Active major bleeding.
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Bacterial endocarditis.
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Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.
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Body weight <50 kg (venous thromboembolism prophylaxis only).
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History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to ARIXTRA.
WARNINGS AND PRECAUTIONS
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Use with caution in patients who have conditions or are taking concomitant medications that increase risk of hemorrhage. (5.1)
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Bleeding risk is increased in renal impairment and in patients with low body weight <50 kg. (5.2, 5.3)
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Thrombocytopenia can occur with administration of ARIXTRA. (5.4)
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Periodic routine complete blood counts (including platelet counts), serum creatinine level, and stool occult blood tests are recommended (5.6)
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The packaging (needle guard) contains dry natural rubber and may cause allergic reactions in latex sensitive individuals (5.7)
ADVERSE REACTIONS
The most common adverse reactions associated with the use of ARIXTRA are bleeding complications. (6.1) Mild local irritation (injection site bleeding, rash, and pruritus) may occur following subcutaneous injection. (6.2)
Anemia, insomnia, increased wound drainage, hypokalemia, dizziness, hypotension, confusion, bullous eruption, hematoma, post-operative hemorrhage, and purpura may occur. (6.4)
To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Discontinue agents that may enhance the risk of hemorrhage prior to initiation of therapy with ARIXTRA unless essential. If co-administration is necessary, monitor patients closely for hemorrhage. (7)
USE IN SPECIFIC POPULATIONS
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Safety and effectiveness of ARIXTRA in pediatric patients have not been established. Because the risk for bleeding during treatment with ARIXTRA is increased in adults who weigh <50 kg, bleeding may be a particular safety concern for use of ARIXTRA in the pediatric population. (4, 5.3)
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Because elderly patients are more likely to have reduced renal function, ARIXTRA should be used with caution in these patients. (8.5)
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The risk of bleeding is increased with reduced renal or hepatic function. (8.6, 8.7)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Prophylaxis of Deep Vein Thrombosis
ARIXTRA® is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE):
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in patients undergoing hip fracture surgery, including extended prophylaxis;
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in patients undergoing hip replacement surgery;
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in patients undergoing knee replacement surgery;
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in patients undergoing abdominal surgery who are at risk for thromboembolic complications.
1.2 Treatment of Acute Deep Vein Thrombosis
ARIXTRA is indicated for the treatment of acute deep vein thrombosis when administered in conjunction with warfarin sodium.
1.3 Treatment of Acute Pulmonary Embolism
ARIXTRA is indicated for the treatment of acute pulmonary embolism when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital.
2 DOSAGE AND ADMINISTRATION
Do not mix other medications or solutions with ARIXTRA. Administer ARIXTRA only subcutaneously.
2.1 Deep Vein Thrombosis Prophylaxis Following Hip Fracture, Hip Replacement, and Knee Replacement Surgery
In patients undergoing hip fracture, hip replacement, or knee replacement surgery, the recommended dose of ARIXTRA is 2.5 mg administered by subcutaneous injection once daily after hemostasis has been established. Administer the initial dose no earlier than 6 to 8 hours after surgery. Administration of ARIXTRA earlier than 6 hours after surgery increases the risk of major bleeding. The usual duration of therapy is 5 to 9 days; up to 11 days of therapy was administered in clinical trials.
In patients undergoing hip fracture surgery, an extended prophylaxis course of up to 24 additional days is recommended. In patients undergoing hip fracture surgery, a total of 32 days (peri-operative and extended prophylaxis) was administered in clinical trials. [See Warnings and Precautions (5.6), Adverse Reactions (6), and Clinical Studies (14).]
2.2 Deep Vein Thrombosis Prophylaxis Following Abdominal Surgery
In patients undergoing abdominal surgery, the recommended dose of ARIXTRA is 2.5 mg administered by subcutaneous injection once daily after hemostasis has been established. Administer the initial dose no earlier than 6 to 8 hours after surgery. Administration of ARIXTRA earlier than 6 hours after surgery increases the risk of major bleeding. The usual duration of administration is 5 to 9 days, and up to 10 days of ARIXTRA was administered in clinical trials.
2.3 Deep Vein Thrombosis and Pulmonary Embolism Treatment
In patients with acute symptomatic DVT and in patients with acute symptomatic PE, the recommended dose of ARIXTRA is 5 mg (body weight <50 kg), 7.5 mg (body weight 50 to 100 kg), or 10 mg (body weight >100 kg) by subcutaneous injection once daily (ARIXTRA treatment regimen). Initiate concomitant treatment with warfarin sodium as soon as possible, usually within 72 hours. Continue treatment with ARIXTRA for at least 5 days and until a therapeutic oral anticoagulant effect is established (INR 2 to 3). The usual duration of administration of ARIXTRA is 5 to 9 days; up to 26 days of ARIXTRA injection was administered in clinical trials. [See Warnings and Precautions (5.6), Adverse Reactions (6), and Clinical Studies (14).]
2.4 Hepatic Impairment
No dose adjustment is recommended in patients with mild to moderate hepatic impairment, based upon single-dose pharmacokinetic data. Pharmacokinetic data are not available for patients with severe hepatic impairment. Patients with hepatic impairment may be particularly vulnerable to bleeding during ARIXTRA therapy. Observe these patients closely for signs and symptoms of bleeding. [See Clinical Pharmacology (12.4).]
2.5 Instructions for Use
ARIXTRA Injection is provided in a single-dose, prefilled syringe affixed with an automatic needle protection system. ARIXTRA is administered by subcutaneous injection. It must not be administered by intramuscular injection. ARIXTRA is intended for use under a physician's guidance. Patients may self-inject only if their physician determines that it is appropriate and the patients are trained in subcutaneous injection techniques.
Prior to administration, visually inspect ARIXTRA to ensure the solution is clear and free of particulate matter.
To avoid the loss of drug when using the prefilled syringe, do not expel the air bubble from the syringe before the injection. Administration should be made in the fatty tissue, alternating injection sites (e.g., between the left and right anterolateral or the left and right posterolateral abdominal wall).
To administer ARIXTRA:
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Wipe the surface of the injection site with an alcohol swab.
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Hold the syringe with either hand and use your other hand to twist the rigid needle guard (covers the needle) counter-clockwise. Pull the rigid needle guard straight off the needle (Figure 1). Discard the needle guard.
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Do not try to remove the air bubbles from the syringe before giving the injection.
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Pinch a fold of skin at the injection site between your thumb and forefinger and hold it throughout the injection.
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Hold the syringe with your thumb on the top pad of the plunger rod and your next 2 fingers on the finger grips on the syringe barrel. Pay attention to avoid sticking yourself with the exposed needle (Figure 2).
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Insert the full length of the syringe needle perpendicularly into the skin fold held between the thumb and forefinger (Figure 3).
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Push the plunger rod firmly with your thumb as far as it will go. This will ensure you have injected all the contents of the syringe (Figure 4).
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When you have injected all the contents of the syringe, the plunger should be released. The plunger will then rise automatically while the needle withdraws from the skin and retracts into the security sleeve. Discard the syringe into the sharps container.
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You will know that the syringe has worked when:
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The needle is pulled back into the security sleeve and the white safety indicator appears above the upper body.
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You may also hear or feel a soft click when the plunger rod is released fully.
3 DOSAGE FORMS AND STRENGTHS
Single-dose, prefilled syringes containing either 2.5 mg, 5 mg, 7.5 mg, or 10 mg of fondaparinux.
4 CONTRAINDICATIONS(What is this?)
ARIXTRA is contraindicated in the following conditions:
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Severe renal impairment (creatinine clearance [CrCl] <30 mL/min). [See Warnings and Precautions (5.2) and Use in Specific Populations (8.6).]
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Active major bleeding.
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Bacterial endocarditis.
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Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.
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Body weight <50 kg (venous thromboembolism [VTE] prophylaxis only) [see Warnings and Precautions (5.3)].
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History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to ARIXTRA.
5 WARNINGS AND PRECAUTIONS
5.1 Hemorrhage
Use ARIXTRA with extreme caution in conditions with increased risk of hemorrhage, such as congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, uncontrolled arterial hypertension, diabetic retinopathy, or shortly after brain, spinal, or ophthalmological surgery. Isolated cases of elevated aPTT temporally associated with bleeding events have been reported following administration of ARIXTRA (with or without concomitant administration of other anticoagulants) [see Adverse Reactions (6.5)].
Do not administer agents that enhance the risk of hemorrhage with ARIXTRA unless essential for the management of the underlying condition, such as vitamin K antagonists for the treatment of VTE. If co-administration is essential, closely monitor patients for signs and symptoms of bleeding.
Do not administer the initial dose of ARIXTRA earlier than 6 to 8 hours after surgery. Administration earlier than 6 hours after surgery increases risk of major bleeding [see Dosage and Administration (2) and Adverse Reactions (6.1)].
5.2 Renal Impairment and Bleeding Risk
ARIXTRA increases the risk of bleeding in patients with impaired renal function due to reduced clearance [see Clinical Pharmacology (12.4)].
The incidence of major bleeding by renal function status reported in clinical trials of patients receiving ARIXTRA for VTE surgical prophylaxis is provided in Table 1. In these patient populations, the following is recommended:
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Do not use ARIXTRA for VTE prophylaxis and treatment in patients with CrCl <30 mL/min [see Contraindications (4)].
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Use ARIXTRA with caution in patients with CrCl 30 to 50 mL/min.
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