Arixtra

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Also seek emergency medical attention if you have symptoms of a spinal blood clot: back pain, numbness or muscle weakness in your lower body, or loss of bladder or bowel control.

Call your doctor at once if you have:

• unusual bleeding (nose, mouth, vagina, or rectum), bleeding from wounds or needle injections, any bleeding that will not stop;
• easy bruising, purple or red pinpoint spots under your skin;
• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
• signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds.

Common side effects may include:

• sleep problems (insomnia);
• mild skin rash;
• dizziness; or
• minor bleeding, rash, or itching where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Mechanism of Action

Antithrombotic agent; inhibits factor Xa, which interrupts blood coagulation cascade and inhibits thrombin formaiton and thrombus development; generally does not increase prothrombin time (PT) or partial thromboplastin time (PTT)

Absorption

Bioavailability: 100%

Peak plasma time: 2-3 hr

Peak plasma concentration: 0.34-0.50 mg/L

Distribution

Protein bound: 94% (antithrombin III)

Vd: 7-11 L

Metabolism

Not established

Elimination

Half-life: 17-21 hr

Dialyzable: Yes

Excretion: Urine

Arixtra is a prescription medication used to treat and prevent blood clots. Arixtra, a "blood thinner", belongs to a group of drugs called factor Xa (ten A) inhibitor anticoagulants. These medications work by decreasing the ability of blood to form clots.

Arixtra comes in an injectable form and is given by injection under the skin once daily.  

Arixtra is part of the drug class:

• Direct factor Xa inhibitors

If you take too much Arixtra, call your doctor or local Poison Control Center right away.

You should not use this medicine if you have ever had a severe allergic reaction to fondaparinux, or if you have:

• active or uncontrolled bleeding;

• severe kidney disease;

• an infection in the lining of your heart (also called bacterial endocarditis); or

• a low level of platelets in your blood after testing positive for a certain antibody while using fondaparinux.

You should not use fondaparinux to prevent blood clots after surgery if you weigh less than 110 pounds (50 kilograms).

Fondaparinux may cause you to bleed more easily, especially if you have:

• a bleeding disorder that is inherited or caused by disease;

• hemorrhagic stroke;

• eye problems caused by diabetes;

• uncontrolled high blood pressure;

• stomach or intestinal bleeding or ulcer;

• recent brain, spine, or eye surgery;

• kidney disease (especially if you are an older adult); or

• if you take a salicylate (aspirin, choline salicylate, diflunisal, magnesium salicylate, salsalate, and others).

Fondaparinux can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural). This type of blood clot could cause long-term paralysis, and may be more likely to occur if:

• you have a genetic spinal defect;

• you have a spinal catheter in place or if a catheter has been recently removed;

• you have a history of spinal surgery or repeated spinal taps;

• you have recently had a spinal tap or epidural anesthesia;

• you are taking an NSAID (nonsteroidal anti-inflammatory drug)--ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac, indomethacin, meloxicam, and others; or

• you are using other medicines to treat or prevent blood clots.

Fondaparinux is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether fondaparinux passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Fondaparinux is usually given every day until your bleeding condition improves. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Fondaparinux is injected under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

You should be sitting or lying down during the injection. Do not inject fondaparinux into a muscle or a vein.

Prepare your dose in a syringe only when you are ready to give yourself an injection. Do not use fondaparinux if it has changed colors or has particles in it. Call your pharmacist for new medication.

Use a different place on your stomach each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

Use a disposable needle only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Tell any doctor who treats you that you are using fondaparinux. If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are using this medication.

While using fondaparinux, your blood and your stool (bowel movement) may need to be tested often. Your nerve and muscle function may also need to be tested.

Store at room temperature away from moisture and heat. Do not freeze.

General

• Evaluate the possibility of an underlying bleeding disorder before initiation of treatment.16 Since coagulation parameters are insensitive for monitoring fondaparinux activity, routine monitoring of such parameters is not required.1 16

Administration

Administer by sub-Q injection; do not give IM.1

Has been administered by direct IV injection† initially in the treatment of acute STEMI†.32

Patients should be sitting or supine during administration.16

Increased risk of major bleeding if administered <6 hours after surgery.1

Sub-Q Administration

Administer by sub-Q injection into fatty tissue, alternating injection sites daily (e.g., between the left and right anterolateral or posterolateral abdominal wall).1 16

Insert the entire length of the needle into a skin fold created by the thumb and forefinger; hold the skin fold, and push the plunger of the syringe the full length of the syringe barrel.1 16 Release the plunger, and the needle automatically withdraws from the skin and retracts into the security sleeve.1 16

Dosage

Dosages for fondaparinux sodium and heparin, heparinoids, or LMWHs cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis1 as they differ in the manufacturing process, anti-factor Xa and antithrombin activity, and dosage.1 10

The activity of fondaparinux sodium is measured based on plasma drug concentrations quantified by anti-Factor Xa activity using fondaparinux as the calibrator.1

Dosage of fondaparinux sodium is expressed in terms of the salt.1

Adults

Patients weighing ≥50 kg: 2.5 mg once daily.1 Manufacturer recommends that initial dose be given no earlier than 6–8 hours after surgery, provided hemostasis has been established.1 Avoid use in patients weighing <50 kg.1 (See Contraindications.)

Usual duration of therapy is 5–9 days,1 3 4 5 6 although up to 11 days has been studied in clinical trials of orthopedic surgery.1 16

Extended prophylaxis: Extended thromboprophylaxis for up to 35 days is recommended in patients undergoing hip fracture surgery,40 1003 and suggested for patients undergoing other major orthopedic procedures.1003

Patients weighing ≥50 kg: 2.5 mg once daily, with the initial dose given 6–8 hours after surgery, provided hemostasis has been established.1 26 Avoid use in patients weighing <50 kg.1 (See Contraindications.)

Usual duration of therapy is 5–9 days, although up to 10 days has been studied.1

Patients weighing <50 kg: 5 mg once daily.1

Patients weighing 50–100 kg: 7.5 mg once daily.1

Patients weighing >100 kg: 10 mg once daily.1

Usual duration of therapy is 5–9 days, although up to 26 days of treatment has been used.1

Initiate concurrent warfarin as soon as possible,1 usually within 72 hours of fondaparinux injection;1 20 ACCP recommends initiating warfarin simultaneously on the first day of fondaparinux treatment.1005

Continue fondaparinux and warfarin for ≥5 days and until an adequate response to warfarin is achieved (i.e., a stable INR of 2–3);1 ACCP recommends continuing concomitant therapy for ≥5 days and until INR of 2–3 has been maintained for ≥24 hours.1 1005

2.5 mg sub-Q once daily has been used.991

Has been administered at an initial dose of 2.5 mg as a single dose by direct IV injection, followed by 2.5 mg sub-Q once daily for the duration of hospitalization or up to 8 days.32

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment.1 Pharmacokinetics not evaluated in patients with severe hepatic impairment.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Contraindicated in patients with severe renal impairment (Clcr <30 mL/minute or Scr ≥3); increased risk for major bleeding episodes.1 32 Exercise caution in patients with other degrees of renal impairment.1

Low Body Weight

Use with caution and decrease dosage to 5 mg once daily for the treatment of DVT or PE in patients weighing <50 kg.1 Contraindicated for prophylaxis of DVT or PE in patients with body weight <50 kg undergoing hip-fracture, hip-replacement, knee-replacement, or abdominal surgery; increased incidence of major bleeding.1

Geriatric Patients

No specific dosage recommendations; however, careful attention to dosage directions recommended.1 (See Specific Populations under Cautions.)

Absorption

Bioavailability

Sub-Q: Absolute bioavailability 100%.1 10 41

Duration

Anticoagulant effects may persist for 2–4 days following discontinuance of therapy in patients with normal renal function (i.e., ≥3–5 half-lives).1

Special Populations

In patients with renal impairment, anticoagulant effects may persist for >2–4 days following discontinuance of therapy.1

Distribution

Extent

In healthy adults, distributes mainly in blood and only to a minor extent in extravascular fluid.1 Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

In vitro, 94% bound to antithrombin III.1

Elimination

Metabolism

Most of dose not metabolized.1

Elimination Route

Eliminated unchanged in urine in individuals with normal renal function.1 41

Half-life

17–21 hours.1

Special Populations

In patients with renal impairment, the total clearance is reduced by 25, 40, and 55% in patients with mild, moderate, and severe renal impairment, respectively, compared with those with normal renal function.1

In geriatric patients >75 years of age, total clearance is approximately 25% lower compared with patients <65 years of age.1

In dialysis-dependent patients, approximately 20% of the drug is removed by hemodialysis.1

In patients weighing <50 kg, total clearance is reduced by approximately 30%.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where this medicine is given.
• Not able to sleep.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

NDC 67457-592-10

Arixtra®
(fondaparinux sodium injection, USP)

2.5 mg/0.5 mL

For Subcutaneous Injection

PHARMACIST: Dispense the accompanying Patient Information
Leaflet to each patient.

Rx only

Contains 10 Single-Dose, Prefilled Syringes
Affixed with an Automatic Needle Protection System

Contents: Each single-dose prefilled syringe contains 2.5 mg of fondaparinux sodium, USP
in 0.5 mL of an isotonic solution of sodium chloride and water for injection.

The needle guard of the prefilled syringe of Arixtra contains dry natural latex rubber that
may cause allergic reactions in latex sensitive individuals.

Recommended Dose: 2.5 mg subcutaneous injection, once daily. See package insert.

Storage: Store at 25°C (77°F); excursions permitted to 15°C - 30°C
(59°F - 86°F). [See USP Controlled Room Temperature.]

Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.

Made in France

MI:592:10C:R3

Mylan.com

Applies to fondaparinux: subcutaneous solution

Along with its needed effects, fondaparinux (the active ingredient contained in Arixtra) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fondaparinux:

• Pale skin
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

• Black, tarry stools
• bladder pain
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest pain
• chills
• collection of blood under the skin
• confusion
• convulsions
• cough
• decreased or cloudy urine
• deep, dark purple bruise
• difficult, burning, or painful urination
• dizziness
• dry mouth
• fainting or lightheadedness when getting up from a lying or sitting position
• fever
• frequent urge to urinate
• increased thirst
• irregular heartbeat
• itching, pain, redness, or swelling at the injection site
• loss of appetite
• lower back or side pain
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in the hands, feet, or lips
• pinpoint red spots on the skin
• red, tender, or oozing skin at incision
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sudden sweating

• Back pain
• bowel or bladder dysfunction
• difficulty with swallowing
• fast heartbeat
• hives, itching, or skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• leg weakness
• numbness
• paralysis
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• tightness in the chest

Get emergency help immediately if any of the following symptoms of overdose occur while taking fondaparinux:

• Abdominal or stomach pain or swelling
• bruising or purple areas on the skin
• coughing up blood
• decreased alertness
• headache
• joint pain or swelling
• nosebleeds

Some side effects of fondaparinux may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty having a bowel movement
• swelling
• trouble sleeping

• Acid or sour stomach
• belching
• diarrhea
• heartburn
• indigestion
• pain
• skin blisters
• stomach discomfort, upset, or pain
• tightness in the chest
• unusual changes to site of surgery
• wound drainage, increased

Applies to fondaparinux: subcutaneous solution

General

The most common adverse events were bleeding events.
The most serious adverse events were bleeding complications and thrombocytopenia.[Ref]

Hematologic

Very common (10% or more): Anemia (19.6%)
Common (1% to 10%): Post-operative hemorrhage, major bleeding, minor bleeding, moderate thrombocytopenia, non-fatal major bleeding at surgical site, overt bleeding associated with a bleeding index of 2 or greater, prothrombin decreased, other clinically overt bleeding, bleeding
Uncommon (0.1% to 1%): Reoperation due to bleeding, non-fatal major bleeding at non-surgical site, severe thrombocytopenia, fatal bleeding, intracranial bleeding, thrombocythemia, abnormal platelets, coagulation disorder
Very rare (less than 0.01%): Hypertensive encephalopathy with intracranial bleeding, minor gastrointestinal bleeding
Postmarketing reports: Thrombocytopenia with thrombosis, aPTT elevation, intracerebral bleeding, retroperitoneal bleeding[Ref]

The majority of major bleeding events occurred during the first 4 days after surgery. Major bleeding incidence increased in patients weighing less than 50 kg and in patients with impaired renal function.[Ref]

Other

Very common (10% or more): Fever (13.6%)
Common (1% to 10%): Edema, post-operative wound infection, wound drainage increased, surgical site reaction, pain, chest pain
Uncommon (0.1% to 1%): Edema peripheral, wound secretion
Rare (less than 0.1%): Hot flushes[Ref]

Gastrointestinal

Very common (10% or more): Nausea (11.3%)
Common (1% to 10%): Constipation, vomiting, diarrhea, dyspepsia, abdominal pain
Rare (less than 0.1%): Gastritis[Ref]

Local

Common (1% to 10%): Hematoma, bruising
Rare (less than 0.1%): Injection site reaction
Frequency not reported: Local irritation (injection site bleeding, rash, pruritus)[Ref]

Hepatic

Common (1% to 10%): Increases in ALT, increases in AST
Uncommon (0.1% to 1%): Hepatic function abnormal, hepatic enzymes increased
Rare (less than 0.1%): Bilirubinemia
Frequency not reported: Increases in bilirubin[Ref]

Cardiovascular

Common (1% to 10%): Hypotension, hypertension[Ref]

Dermatologic

Common (1% to 10%): Rash, purpura, bullous eruption (includes localized blister)
Uncommon (0.1% to 1%): Pruritus
Rare (less than 0.1%): Flushing[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness
Rare (less than 0.1%): Somnolence, vertigo, fatigue, syncope
Postmarketing reports: Spinal or epidural hematoma[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection, urinary retention
Rare (less than 0.1%): Edema genital[Ref]

Metabolic

Common (1% to 10%): Hypokalemia[Ref]

Musculoskeletal

Common (1% to 10%): Leg pain, back pain[Ref]

Psychiatric

Common (1% to 10%): Insomnia, confusion
Uncommon (0.1% to 1%): Anxiety[Ref]

Respiratory

Common (1% to 10%): Pneumonia, coughing, epistaxis
Rare (less than 0.1%): Dyspnea[Ref]

Hypersensitivity

Rare (less than 0.1%): Allergic reaction
Very rare (less than 0.01%): Angioedema, anaphylactoid/anaphylactic reaction
Postmarketing reports: Serious allergic reactions[Ref]

Some side effects of Arixtra may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.