Arixtra

Name: Arixtra

Arixtra and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Arixtra falls into category B. There are no well-done studies that have been done in humans with Arixtra. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

 

Arixtra FDA Warning

WARNING: SPINAL/EPIDURAL HEMATOMAS

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH), heparinoids, or Arixtra 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 non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants
  • a history of traumatic or repeated epidural or spinal puncture
  • 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.

What should I avoid while using Arixtra (fondaparinux)?

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Arixtra (fondaparinux) side effects

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.

Introduction

Anticoagulant; a synthetic activated factor Xa inhibitor.

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not mix with other injections or infusions.1

Before Using Arixtra

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of fondaparinux in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fondaparinux in the elderly. However, elderly patients are more likely to have bleeding problems and age-related kidney disease, which may require caution or an adjustment in the dose for patients receiving fondaparinux.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Defibrotide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Abciximab
  • Aceclofenac
  • Acemetacin
  • Alipogene Tiparvovec
  • Alteplase, Recombinant
  • Amtolmetin Guacil
  • Anagrelide
  • Anistreplase
  • Apixaban
  • Argatroban
  • Aspirin
  • Bemiparin
  • Betrixaban
  • Bivalirudin
  • Bromfenac
  • Bufexamac
  • Cangrelor
  • Celecoxib
  • Chamomile
  • Choline Salicylate
  • Cilostazol
  • Citalopram
  • Clonixin
  • Clopidogrel
  • Collagenase, Clostridium histolyticum
  • Dabigatran Etexilate
  • Dalteparin
  • Danaparoid
  • Desvenlafaxine
  • Dexibuprofen
  • Dexketoprofen
  • Diclofenac
  • Diflunisal
  • Dipyridamole
  • Dipyrone
  • Drotrecogin Alfa
  • Droxicam
  • Edoxaban
  • Enoxaparin
  • Epoprostenol
  • Eptifibatide
  • Escitalopram
  • Etodolac
  • Etofenamate
  • Etoricoxib
  • Felbinac
  • Fenofibrate
  • Fenofibric Acid
  • Fenoprofen
  • Fepradinol
  • Feprazone
  • Floctafenine
  • Flufenamic Acid
  • Fluoxetine
  • Flurbiprofen
  • Fluvoxamine
  • Garlic
  • Ginkgo
  • Ibuprofen
  • Iloprost
  • Indomethacin
  • Ketoprofen
  • Ketorolac
  • Levomilnacipran
  • Lornoxicam
  • Loxoprofen
  • Lumiracoxib
  • Meclofenamate
  • Mefenamic Acid
  • Meloxicam
  • Milnacipran
  • Morniflumate
  • Nabumetone
  • Nadroparin
  • Naproxen
  • Nepafenac
  • Niflumic Acid
  • Nimesulide
  • Nimesulide Beta Cyclodextrin
  • Nintedanib
  • Orlistat
  • Oxaprozin
  • Oxyphenbutazone
  • Papaya
  • Parecoxib
  • Paroxetine
  • Pentosan Polysulfate Sodium
  • Phenylbutazone
  • Piketoprofen
  • Piracetam
  • Piroxicam
  • Pranoprofen
  • Prasugrel
  • Proglumetacin
  • Propyphenazone
  • Proquazone
  • Reteplase, Recombinant
  • Rivaroxaban
  • Rofecoxib
  • Selexipag
  • Sertraline
  • St John's Wort
  • Streptokinase
  • Sulfinpyrazone
  • Sulindac
  • Tan-Shen
  • Tenecteplase
  • Tenoxicam
  • Tiaprofenic Acid
  • Ticlopidine
  • Tirofiban
  • Tolfenamic Acid
  • Tolmetin
  • Treprostinil
  • Urokinase
  • Valdecoxib
  • Venlafaxine
  • Vilazodone
  • Vorapaxar
  • Vortioxetine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Chondroitin
  • Coenzyme Q10
  • Curcumin
  • Dong Quai
  • Ginger
  • Vitamin A

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Avocado

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bleeding problems or
  • Blood vessel problems or
  • Catheter insertion in the spine or
  • Diabetic retinopathy (eye problem) or
  • Hypertension (high blood pressure), uncontrolled or
  • Liver disease or
  • Stomach or bowel problems (eg, ulcers), active or
  • Stroke, recent or history of or
  • Surgery (eg, eye, brain, or spine), recent or history of—Use with caution. The risk of bleeding may be increased.
  • Heart infection or
  • Kidney disease, severe or
  • Major bleeding, active or
  • Thrombocytopenia (low platelet count in the blood) or
  • Weight of less than 110 pounds—Should not be used in patients with these conditions.
  • Kidney disease—Use with caution. The effects may be increased because of slower removal from the body.

Precautions While Using Arixtra

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests will be needed to check for unwanted effects. Be sure to keep all appointments.

Fondaparinux may cause bleeding problems. This risk is higher if you have a catheter in your back for pain medicine or anesthesia (sometimes called an "epidural"), or if you have kidney problems. The risk of bleeding increases if your kidney problems get worse. Check with your doctor right away if you have any unusual bleeding or bruising, black, tarry stools, bleeding gums, blood in the urine or stools, tingling, numbness, or weakness of the lower legs, or pinpoint red spots on your skin.

You may bleed or bruise more easily while you are using this medicine. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Be careful when using sharp objects, including razors and fingernail clippers. Avoid nose picking and forceful nose blowing.

Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using fondaparinux several days before having surgery or medical tests.

Also, tell your doctor if you have received fondaparinux or heparin before and had a reaction called thrombocytopenia (low platelet count in the blood), or if new blood clots formed while you were receiving the medicine.

This medicine may increase your risk of having spinal or epidural blood clots when it is used together with certain other medicines or procedures. Check with your doctor right away if you have midline back pain, numbness, tingling, or weakness in the legs or feet, or loss of control of the bowel or bladder (incontinence).

The needle guard of the prefilled syringe of this medicine contains dry natural latex rubber. Tell your doctor if you have any allergies with latex or rubber.

Check with your doctor before you start or stop taking any other medicine, or change the amount you are taking. This includes prescription or nonprescription (over-the-counter [OTC]) medicines, and herbal or vitamin supplements. Many medicines change the way this medicine affects your body.

How do I store and/or throw out Arixtra?

  • Store at room temperature. Do not freeze.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Arixtra - Clinical Pharmacology

 Mechanism of Action

The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, fondaparinux sodium potentiates (about 300 times) the innate neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development.

Fondaparinux sodium does not inactivate thrombin (activated Factor II) and has no known effect on platelet function. At the recommended dose, fondaparinux sodium does not affect fibrinolytic activity or bleeding time.

 Pharmacodynamics

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 LMWH are not appropriate for this use.) As a result, the activity of fondaparinux sodium is expressed as milligrams (mg) of the fondaparinux calibrator. The anti-Xa activity of the drug increases with increasing drug concentration, reaching maximum values in approximately three hours.

 Pharmacokinetics

Absorption

Fondaparinux sodium administered by subcutaneous injection is rapidly and completely absorbed (absolute bioavailability is 100%). Following a single subcutaneous dose of fondaparinux sodium 2.5 mg in young male subjects, Cmax of 0.34 mg/L is reached in approximately 2 hours. In patients undergoing treatment with fondaparinux sodium injection 2.5 mg, once daily, the peak steady-state plasma concentration is, on average, 0.39 to 0.50 mg/L and is reached approximately 3 hours post-dose. In these patients, the minimum steady-state plasma concentration is 0.14 to 0.19 mg/L. 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 to 100 kg), and 10 mg (body weight >100 kg) once daily, the body–weight-adjusted doses provide similar mean steady-state peaks and minimum plasma concentrations across all body weight categories. The mean peak steady-state plasma concentration is in the range of 1.20 to 1.26 mg/L. In these patients, the mean minimum steady-state plasma concentration is in the range of 0.46 to 0.62 mg/L.

Distribution

In healthy adults, intravenously or subcutaneously administered fondaparinux sodium distributes mainly in blood and only to a minor extent in extravascular fluid as evidenced by steady state and non-steady state apparent volume of distribution of 7 to 11 L. Similar fondaparinux distribution occurs in patients undergoing elective hip surgery or hip fracture surgery. In vitro, fondaparinux sodium is highly (at least 94%) and specifically bound to antithrombin III (ATIII) and does not bind significantly to other plasma proteins (including platelet Factor 4 [PF4]) or red blood cells.

Metabolism

In vivo metabolism of fondaparinux has not been investigated since the majority of the administered dose is eliminated unchanged in urine in individuals with normal kidney function.

Elimination

In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug. In healthy individuals up to 75 years of age, up to 77% of a single subcutaneous or intravenous fondaparinux dose is eliminated in urine as unchanged drug in 72 hours. The elimination half-life is 17 to 21 hours.

Special Populations

Renal Impairment

Fondaparinux elimination is prolonged in patients with renal impairment 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 impairment (CrCl 50 to 80 mL/min), approximately 40% lower in patients with moderate renal impairment (CrCl 30 to 50 mL/min), and approximately 55% lower in patients with severe renal impairment (<30 mL/min) compared to patients with normal renal function. A similar relationship between fondaparinux clearance and extent of renal impairment was observed in DVT treatment patients. [See Contraindications (4) and Warnings and Precautions (5.3).]

Hepatic Impairment

Following a single, subcutaneous dose of 7.5 mg of Arixtra in patients with moderate hepatic impairment (Child-Pugh Category B), Cmax and AUC were decreased by 22% and 39%, respectively, compared to subjects with normal liver function. The changes from baseline in pharmacodynamic parameters, such as aPTT, PT/INR, and antithrombin III, were similar in normal subjects and in patients with moderate hepatic impairment. Based on these data, no dosage adjustment is recommended in these patients. However, a higher incidence of hemorrhage was observed in subjects with moderate hepatic impairment than in normal subjects [see Use in Specific Populations (8.7)]. The pharmacokinetics of fondaparinux have not been studied in patients with severe hepatic impairment. [See Dosage and Administration (2.4).]

Pediatric

The pharmacokinetics of fondaparinux have not been investigated in pediatric patients. [See Contraindications (4), Warnings and Precautions (5.4), and Pediatric Use (8.4).]

Geriatric

Fondaparinux elimination is prolonged in patients older than 75 years. 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 older than 75 years as compared to patients younger than 65 years. A similar relationship between fondaparinux clearance and age was observed in DVT treatment patients. [See Use in Specific Populations (8.5).]

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 (2.3) and Contraindications (4)].

Gender

The pharmacokinetic properties of fondaparinux sodium are not significantly affected by gender.

Race

Pharmacokinetic differences due to race have not been studied prospectively. However, studies performed in Asian (Japanese) healthy subjects did not reveal a different pharmacokinetic profile compared to Caucasian healthy subjects. Similarly, no plasma clearance differences were observed between black and Caucasian patients undergoing orthopedic surgery.

Patient Counseling Information

See FDA-Approved Patient Labeling (17.2)

Patient Advice

If the patients have had neuraxial anesthesia or spinal puncture, and particularly, if they are taking concomitant NSAIDS, platelet inhibitors, or other anticoagulants, they should be informed to watch for signs and symptoms of spinal or epidural hematomas, such as back pain, tingling, numbness (especially in the lower limbs), muscular weakness, and stool or urine incontinence. If any of these symptoms occur, the patients should contact his or her physician immediately.

The use of aspirin and other NSAIDS may enhance the risk of hemorrhage. Their use should be discontinued prior to Arixtra therapy whenever possible; if co-administration is essential, the patient’s clinical and laboratory status should be closely monitored. [See Drug Interactions (7).]

If patients must self-administer Arixtra (e.g., if Arixtra is used at home), they should be advised of the following:

• Arixtra should be given by subcutaneous injection. Patients must be instructed in the proper technique for administration. • The most important risk with Arixtra administration is bleeding. Patients should be counseled on signs and symptoms of possible bleeding. • It may take them longer than usual to stop bleeding. • They may bruise and/or bleed more easily when they are treated with Arixtra. • They should report any unusual bleeding, bruising, or signs of thrombocytopenia (such as a rash of dark red spots under the skin) to their physician [see Warnings and Precautions (5.2, 5.5)]. • To tell their physicians and dentists they are taking Arixtra and/or any other product known to affect bleeding before any surgery is scheduled and before any new drug is taken [see Warnings and Precautions (5.2)]. • To tell their physicians and dentists of all medications they are taking, including those obtained without a prescription, such as aspirin or other NSAIDs. [See Drug Interactions (7).]

Keep out of the reach of children.

FDA-Approved Patient Labeling

Patient labeling is provided as a tear-off leaflet at the end of this full prescribing information.

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

Manufactured by:
Aspen Notre Dame de Bondeville
Notre Dame de Bondeville, France

Revised: 8/2017
MI:ARXTIJ:R4p

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