Erlotinib

Generic Name: erlotinib (er LOE ti nib)

Brand Names: Tarceva

What is erlotinib?

Erlotinib is a cancer medication that interferes with the growth of cancer cells and slows their spread in the body.

Erlotinib is used to treat non-small cell lung cancer. Erlotinib is also used in combination with other cancer medicine to treat pancreatic cancer.

Erlotinib may also be used for purposes not listed in this medication guide.

What is the most important information I should know about erlotinib?

Do not take erlotinib if you are pregnant. It could harm the unborn baby. Use effective birth control while you are taking this medication and for at least 2 weeks after your treatment ends.

Before taking erlotinib, tell your doctor if you have lung problems (other than lung cancer), kidney or liver disease, if you are dehydrated, or if you smoke.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. This will help your doctor determine how long to treat you with erlotinib. Visit your doctor regularly.

Avoid exposure to sunlight or tanning beds. Erlotinib can cause skin rash, dryness, or other irritation. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Avoid using skin products that can cause dryness or irritation. Stop taking erlotinib and call your doctor at once if you have new or worsening lung problems (chest pain, dry cough with fever, wheezing, feeling short of breath), chest pain spreading to the arm or shoulder, sudden numbness or weakness, eye pain or irritation, rapid weight gain, urinating less than usual or not at all, severe or ongoing diarrhea or vomiting, coughing up blood, black or bloody stools, pale skin, easy bruising or bleeding, mouth sores, or a severe skin rash. There are many other drugs that can interact with erlotinib. Tell your doctor about all medications you use. Keep a list of all your medicines and show it to any healthcare provider who treats you.

What should I discuss with my healthcare provider before taking erlotinib?

You should not take erlotinib if you are allergic to it.

If you have any of these other conditions, you may need a dose adjustment or special tests:

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  lung or breathing problems (other than lung cancer);

  
  


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  kidney disease;

  
  


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  liver disease;

  
  


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  if you are dehydrated; or

  
  


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  if you smoke.

  
  

FDA pregnancy category D. Do not take erlotinib if you are pregnant. It could harm the unborn baby. Use effective birth control while you are taking this medication and for at least 2 weeks after your treatment ends. It is not known whether erlotinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking erlotinib.

How should I take erlotinib?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take erlotinib on an empty stomach, at least 1 hour before or 2 hours after eating. Do not crush an erlotinib tablet. The medicine from a crushed or broken pill can be dangerous if it gets on your skin. If this occurs, wash your skin with soap and water and rinse thoroughly.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. This will help your doctor determine how long to treat you with erlotinib. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

See also: Erlotinib dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember (take only on an empty stomach). Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe diarrhea, severe skin rash, dark urine, stomach pain, or jaundice (yellowing of your skin or eyes).

What should I avoid while using erlotinib?

Avoid taking an antacid within several hours before or after you take erlotinib. Avoid exposure to sunlight or tanning beds. Erlotinib can cause skin rash, dryness, or other irritation. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Avoid using skin products that can cause dryness or irritation, such as acne medications, harsh soaps or skin cleansers, or skin products that contain alcohol.

Avoid smoking. It can make erlotinib less effective.

Grapefruit and grapefruit juice may interact with erlotinib and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Erlotinib side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop taking erlotinib and call your doctor at once if you have a serious side effect such as:

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  new or worsening lung problems such as chest pain, dry cough with fever, wheezing, rapid breathing, feeling short of breath;

  
  


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  chest pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

  
  


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  sudden numbness or weakness, sudden severe headache, or problems with vision, speech, or balance;

  
  


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  eye pain, redness, or irritation;

  
  


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  confusion, mood changes, increased thirst, urinating less than usual or not at all;

  
  


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  swelling, rapid weight gain;

  
  


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  severe or ongoing diarrhea, vomiting, or loss of appetite;

  
  


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  black, bloody, or tarry stools;

  
  


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  coughing up blood or vomit that looks like coffee grounds;

  
  


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  pale or yellowed skin, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  
  


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  white patches or sores inside your mouth or on your lips;

  
  


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  fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;

  
  


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  the first sign of any type of skin rash, no matter how mild; or

  
  


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  nausea, upper stomach pain, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

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  mild stomach upset, nausea, or diarrhea;

  
  


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  weight loss;

  
  


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  acne, dry skin; or

  
  


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  tired feeling.

  
  

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.

Erlotinib Dosing Information

Usual Adult Dose for Non-Small Cell Lung Cancer:

Initial dose: 150 mg once a day

The dose should be taken at least one hour before or two hours after ingestion of food.

Treatment should continue until disease progression or unacceptable toxicity occurs. There is no evidence that treatment beyond progression is beneficial.

Usual Adult Dose for Pancreatic Cancer:

Initial dose: 100 mg once a day

The dose should be taken at least one hour before or two hours after ingestion of food.

Treatment should continue until disease progression or unacceptable toxicity occurs.

What other drugs will affect erlotinib?

Many drugs can interact with erlotinib. Below is just a partial list. Tell your doctor if you are using:

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  a blood thinner such as warfarin (Coumadin);

  
  


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  bosentan (Tracleer);

  
  


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  conivaptan (Vaprisol);

  
  


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  dexamethasone (Decadron, Hexadrol);

  
  


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  imatinib (Gleevec);

  
  


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  isoniazid (for treating tuberculosis);

  
  


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  St. John's wort;

  
  


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  steroid medicine (prednisone and others);

  
  


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  an antibiotic such as ciprofloxacin (Cipro), clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), rifapentine (Priftin), or telithromycin (Ketek);

  
  


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  an antidepressant such as nefazodone;

  
  


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  antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend);

  
  


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  a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Solfoton);

  
  


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  heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others;

  
  


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  HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir), or saquinavir (Invirase);

  
  


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  medicines to treat narcolepsy, such as armodafanil (Nuvigil) or modafanil (Progivil);

  
  


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  NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin, ibuprofen (Motrin, Advil), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others; or

  
  


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  seizure medication such as carbamazepine (Carbatrol, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline).

  
  

This list is not complete and there are many other drugs that can interact with erlotinib. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More erlotinib resources

• Erlotinib Side Effects (in more detail)
• Erlotinib Dosage
• Erlotinib Use in Pregnancy & Breastfeeding
• Erlotinib Drug Interactions
• Erlotinib Support Group
• 13 Reviews for Erlotinib - Add your own review/rating

• erlotinib Advanced Consumer (Micromedex) - Includes Dosage Information


• Erlotinib Professional Patient Advice (Wolters Kluwer)


• Erlotinib MedFacts Consumer Leaflet (Wolters Kluwer)


• Erlotinib Monograph (AHFS DI)


• Tarceva Prescribing Information (FDA)


• Tarceva Consumer Overview

Compare erlotinib with other medications

• Non-Small Cell Lung Cancer
• Pancreatic Cancer
• Renal Cell Carcinoma

Where can I get more information?

• Your pharmacist can provide more information about erlotinib.

See also: erlotinib side effects (in more detail)

Firmagon

degarelix acetate

Dosage Form: powder, metered, for subcutaneous injection
FULL PRESCRIBING INFORMATION

Indications and Usage for Firmagon

Firmagon is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer.

Firmagon Dosage and Administration

Firmagon is for subcutaneous administration only and is not to be administered intravenously.

Dosing information:

Starting dose	Maintenance dose – Administration every 28 days
240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL	80 mg given as one subcutaneous injection at a concentration of 20 mg/mL

The first maintenance dose should be given 28 days after the starting dose.

Firmagon is administered as a subcutaneous injection in the abdominal region. As with other drugs administered by subcutaneous injection, the injection site should vary periodically. Injections should be given in areas of the abdomen that will not be exposed to pressure, e.g. not close to waistband or belt nor close to the ribs.

Firmagon is supplied as a powder to be reconstituted with Sterile Water for Injection, USP (WFI). The reconstitution procedure needs to be carefully followed. Administration of other concentrations is not recommended.  See Instructions for Proper Use.

Instructions for Proper Use

NOTE:

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  Gloves should be worn during preparation and administration

  
  


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  Reconstituted drug must be administered within one hour after addition of Sterile Water for Injection, USP (WFI)

  
  


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  Keep the vials vertical at all times

  
  


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  Do not shake the vials

  
  


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  Follow aseptic technique

  
  

Firmagon 120 mg

The Treatment Initiation pack contains 2 vials of Firmagon 120 mg that must be prepared for 2 subcutaneous injections. Hence, the instructions here below need to be repeated a second time.

Prepare Firmagon 120 mg for reconstitution by gathering the following:

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  6 mL of Sterile Water for Injection, USP (WFI); Do not use Bacteriostatic Water for Injection

  
  


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  2 reconstitution needles – 21G / 2 inch

  
  


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  2 administration needles for subcutaneous injection – 27G / 1-1/4 inch

  
  


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  2 injection syringes (5 mL)

  
  

1. 
   

   Draw up 3 mL WFI with a reconstitution needle (21G / 2 in).

   
   


2. 
   

   Inject the WFI slowly into the Firmagon 120 mg vial. To keep the product and syringe sterile, do not remove the syringe and the needle.

   
   


3. 
   

   Keeping the vial in an upright position, swirl it very gently until the liquid looks clear and without undissolved powder or particles. If the powder adheres to the vial over the liquid surface, the vial can be tilted slightly to dissolve powder. Avoid shaking to prevent foam formation.  A ring of small air bubbles on the surface of the liquid is acceptable. The reconstitution procedure may take up to 15 minutes.

   
   


4. 
   

   Tilt the vial slightly and keep the needle in the lowest part of the vial. Withdraw 3 mL of Firmagon 120 mg without turning the vial upside down.

   
   


5. 
   

   Exchange the reconstitution needle with the administration needle for deep subcutaneous injection (27G / 1-1/4 in). Remove any air bubbles.

   
   


6. 
   

   Inject 3 mL of Firmagon 120 mg subcutaneously immediately after reconstitution.

   
   
   • Grasp the skin of the abdomen, elevate the subcutaneous tissue. Insert the needle deeply at an angle of not less than 45 degrees.
   
   
   • Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the reconstituted product can no longer be used. Discontinue the procedure and discard the syringe and the needle (reconstitute a new dose for the patient).
   
   


7. Repeat reconstitution procedure for the second dose. Choose a different injection site and inject 3 mL.

Firmagon 80 mg

The Treatment Maintenance pack contains 1 vial of Firmagon 80 mg that must be prepared for subcutaneous injection.

Prepare Firmagon 80 mg for reconstitution by gathering the following:

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  4.2 mL of Sterile Water for Injection, USP (WFI); Do not use Bacteriostatic Water for Injection

  
  


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  1 reconstitution needle – 21G / 2 inch

  
  


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  1 administration needle for subcutaneous injection – 27G / 1-1/4 inch

  
  


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  1 injection syringe (5 mL)

  
  

1. 
   

   Draw up 4.2 mL WFI with the reconstitution needle (21G / 2 in).

   
   


2. 
   

   Inject the WFI slowly into the Firmagon 80 mg vial. To keep the product and syringe sterile, do not remove the syringe and the needle.

   
   


3. 
   

   Keeping the vial in an upright position, swirl it very gently until the liquid looks clear and without undissolved powder or particles. If the powder adheres to the vial over the liquid surface, the vial can be tilted slightly to dissolve powder. Avoid shaking to prevent foam formation.  A ring of small air bubbles on the surface of the liquid is acceptable. The reconstitution procedure may take up to 15 minutes.

   
   


4. 
   

   Tilt the vial slightly and keep the needle in the lowest part of the vial. Withdraw 4 mL of Firmagon 80 mg without turning the vial upside down.

   
   


5. 
   

   Exchange the reconstitution needle with the administration needle for deep subcutaneous injection (27G / 1-1/4 in). Remove any air bubbles.

   
   


6. 
   

   Inject 4 mL of Firmagon 80 mg subcutaneously immediately after reconstitution:

   
   

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  Grasp the skin of the abdomen, elevate the subcutaneous tissue. Insert the needle deeply at an angle of not less than 45 degrees.

  
  


• 
  

  Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the reconstituted product can no longer be used. Discontinue the procedure and discard the syringe and the needle (reconstitute a new dose for the patient).

  
  

Dosage Forms and Strengths

Starting dose

Powder for injection 120 mg:

One vial of Firmagon 120 mg contains 120 mg of degarelix. Each vial is to be reconstituted with 3 mL of Sterile Water for Injection. 3 mL is withdrawn to deliver 120 mg degarelix at a concentration of 40 mg/mL. One starting dose comprises 240 mg given as two 3 mL injections of 120 mg each.

Maintenance dose

Powder for injection 80 mg:

One vial of Firmagon 80 mg contains 80 mg of degarelix. Each vial is to be reconstituted with 4.2 mL of Sterile Water for Injection. 4 mL is withdrawn to deliver 80 mg degarelix at a concentration of 20 mg/mL. One maintenance dose comprises 80 mg given as one 4 mL injection.

Contraindications

Firmagon is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components.

Degarelix is contraindicated in women who are or may become pregnant. Degarelix can cause fetal harm when administered to a pregnant woman.  Degarelix given to rabbits during organogenesis at doses that were 0.02% of the clinical loading dose (240 mg) on a mg/m2 basis caused embryo/fetal lethality and abortion.  When degarelix was given to female rats during organogenesis, at doses that were just 0.036% of the clinical loading dose on a mg/m2 basis, there was an increase post implantation loss and a decrease in the number of live fetuses.  If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Warnings and Precautions

Use in Pregnancy

Pregnancy Category X

Women who are or may become pregnant should not take Firmagon. [see Contraindications (4) and Use in Specific Populations (8.1)]

Effect on QT/QTc Interval

Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.

In the randomized, active-controlled trial comparing Firmagon to leuprolide, periodic electrocardiograms were performed. Seven patients, three (<1%) in the pooled degarelix group and four (2%) patients in the leuprolide 7.5 mg group, had a QTcF > 500 msec.  From baseline to end of study the median change for Firmagon was 12.3 msec and for leuprolide was 16.7 msec.

Laboratory Testing

Therapy with Firmagon results in suppression of the pituitary gonadal system. Results of diagnostic tests of the pituitary gonadotropic and gonadal functions conducted during and after Firmagon may be affected. The therapeutic effect of Firmagon should be monitored by measuring serum concentrations of prostate-specific antigen (PSA) periodically. If PSA increases, serum concentrations of testosterone should be measured.

Adverse Reactions

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 1325 patients with prostate cancer received Firmagon either as a monthly treatment (60-160 mg) or as a single dose (up to 320 mg).  A total of 1032 patients (78%) were treated for at least 6 months and 853 patients (64%) were treated for one year or more.  The most commonly observed adverse reactions during Firmagon therapy included injection site reactions (e.g., pain, erythema, swelling, or induration), hot flashes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT). The majority of the adverse reactions were Grade 1 or 2, with Grade 3/4 adverse reaction incidences of 1% or less.

Firmagon was studied in an active-controlled trial (N = 610) in which patients with prostate cancer were randomized to receive Firmagon (subcutaneous) or leuprolide (intramuscular) monthly for 12 months. Adverse reactions reported in 5% of patients or more are shown in Table 1.

Table 1. Adverse Reactions Reported in ≥ 5% of Patients in an Active Controlled Study 

	Firmagon 240/160 mg (subcutaneous) N = 202	Firmagon 240/80 mg (subcutaneous) N = 207	Leuprolide 7.5 mg (intramuscular) N = 201
Percentage of subjects with adverse events	83%	79%	78%
Body as a whole
Injection site adverse events	44%	35%	<1%
Weight increase	11%	9%	12%
Fatigue	6%	3%	6%
Chills	4%	5%	0%
Cardiovascular system
Hot flash	26%	26%	21%
Hypertension	7%	6%	4%
Musculoskeletal system
Back pain	6%	6%	8%
Arthralgia	4%	5%	9%
Urogenital system
Urinary tract infection	2%	5%	9%
Digestive system
Increases in Transaminases and GGT	10%	10%	5%
Constipation	3%	5%	5%

The most frequently reported adverse reactions at the injection sites were pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These adverse reactions were mostly transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%).  Grade 3 injection site reactions occurred in 2% or less of patients receiving degarelix.

Hepatic laboratory abnormalities were primarily Grade 1 or 2 and were generally reversible. Grade 3 hepatic laboratory abnormalities occurred in less than 1% of patients.

In 1-5% of patients the following adverse reactions, not already listed, were considered related to Firmagon by the investigator:

Body as a whole: Asthenia, fever, night sweats; Digestive system: Nausea; Nervous system: Dizziness, headache, insomnia.

The following adverse reactions, not already listed, were reported to be drug-related by the investigator in ≥1% of patients: erectile dysfunction, gynecomastia, hyperhidrosis, testicular atrophy, and diarrhea.

Changes in bone density:

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of medical castration in men will result in decreased bone density.

Anti-degarelix antibody development has been observed in 10% of patients after treatment with Firmagon for 1 year. There is no indication that the efficacy or safety of Firmagon treatment is affected by antibody formation.

Drug Interactions

No drug-drug interaction studies were conducted.

Degarelix is not a substrate for the human CYP450 system.  Degarelix is not an inducer or inhibitor of the CYP450 system in vitro.   Therefore, clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely.

USE IN SPECIFIC POPULATIONS

Pregnancy

Category X  [see Contraindications (4) and Warnings and Precautions (5.1)]

Women who are or may become pregnant should not take Firmagon. When degarelix was given to rabbits during early organogenesis at doses of 0.002 mg/kg/day (about 0.02% of the clinical loading dose on a mg/m2 basis), there was an increase in early post-implantation loss. Degarelix given to rabbits during  mid and late organogenesis at doses of 0.006 mg/kg/day (about 0.05% of the clinical loading dose on a mg/m2 basis) caused embryo/fetal lethality and abortion.  When degarelix was given to female rats during early organogenesis, at doses of 0.0045 mg/kg/day (about 0.036% of the clinical loading dose on a mg/m2 basis), there was an increase in early post-implantation loss.  When degarelix was given to female rats during mid and late organogenesis, at doses of 0.045 mg/kg/day (about 0.36% of the clinical loading dose on a mg/m2 basis), there was an increase in the number of minor skeletal abnormalities and variants.

Nursing Mothers

Firmagon is not indicated for use in women and is contraindicated in women who are or who may become pregnant.  It is not known whether this drug is excreted in human milk.  Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from degarelix, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the total number of subjects in clinical studies of Firmagon, 82% were age 65 and over, while 42% were age 75 and over.   No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

No pharmacokinetic studies in renally impaired patients have been conducted. At least 20-30% of a given dose of degarelix is excreted unchanged in the urine.

A population pharmacokinetic analysis of data from the randomized study demonstrated that there is no significant effect of mild renal impairment [creatinine clearance (CrCL) 50-80 mL/min] on either the degarelix concentration or testosterone concentration.  Data on patients with moderate or severe renal impairment is limited and therefore degarelix should be used with caution in patients with CrCL < 50 mL/min.

Hepatic Impairment

Patients with hepatic impairment were excluded from the randomized trial.

A single dose of 1 mg degarelix administered as an intravenous infusion over 1 hour was studied in 16 non-prostate cancer patients with either mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Compared to non-prostate cancer patients with normal liver function, the exposure of degarelix decreased by 10% and 18% in patients with mild and moderate hepatic impairment, respectively.  Therefore, dose adjustment is not necessary in patients with mild or moderate hepatic impairment.  However, since hepatic impairment can lower degarelix exposure, it is recommended that in patients with hepatic impairment testosterone concentrations should be monitored on a monthly basis until medical castration is achieved.  Once medical castration is achieved, an every-other-month testosterone monitoring approach could be considered.

Patients with severe hepatic dysfunction have not been studied and caution is therefore warranted in this group.

Overdosage

There have been no reports of overdose with Firmagon. In the case of overdose, however, discontinue Firmagon, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

SEE Firmagon PATIENT COUNSELING INFORMATION

Firmagon Description

Firmagon is a sterile lyophilized powder for injection containing degarelix (as the acetate) and mannitol. Degarelix is a synthetic linear decapeptide amide containing seven unnatural amino acids, five of which are D-amino acids. The acetate salt of degarelix is a white to off-white amorphous powder of low density as obtained after lyophilization.

The chemical name of degarelix is D-Alaninamide, N - acetyl - 3 - (2 - naphthalenyl) - D - alanyl - 4 - chloro - D - phenylalanyl - 3 - (3 - pyridinyl) - D - alanyl - L - seryl - 4 - [[[(4S) - hexahydro - 2,6 - dioxo - 4 - pyrimidinyl]carbonyl]amino] - L phenylalanyl-4-[(aminocarbonyl)amino]-D-phenylalanyl-L leucyl-N6–(1-methylethyl)-L-lysyl-L-prolyl. It has an empirical formula of C82H103N18O16Cl and a molecular weight of 1632.3 Da.

Degarelix has the following structural formula:

Firmagon delivers degarelix acetate, equivalent to 120 mg of degarelix for the starting dose, and 80 mg of degarelix for the maintenance dose. The 80 mg vial contains 200 mg mannitol and the 120 mg vial contains 150 mg mannitol.

Firmagon - Clinical Pharmacology

Mechanism of Action

Degarelix is a GnRH receptor antagonist.  It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone.

Pharmacodynamics

A single dose of 240 mg Firmagon causes a decrease in the plasma concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and subsequently testosterone.

Firmagon is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL.

Figure 1: Plasma Testosterone Levels from Day 0 to 364 for Degarelix 240 mg/80 mg (Median with Interquartile Ranges)

Pharmacokinetics

Absorption

Firmagon forms a depot upon subcutaneous administration, from which degarelix is released to the circulation.  Following administration of Firmagon 240 mg at a product concentration of 40 mg/mL, the mean Cmax was 26.2 ng/mL (coefficient of variation, CV 83%) and the mean AUC was 1054 ng•day/mL (CV 35%). Typically Cmax occurred within 2 days after subcutaneous administration.  In prostate cancer patients at a product concentration of 40 mg/mL, the pharmacokinetics of degarelix were linear over a dose range of 120 to 240 mg. The pharmacokinetic behavior of the drug is strongly influenced by its concentration in the injection solution.

Distribution

The distribution volume of degarelix after intravenous (> 1 L/kg) or subcutaneous administration (> 1000L) indicates that degarelix is distributed throughout total body water.  In vitro plasma protein binding of degarelix is estimated to be approximately 90%.

Metabolism

Degarelix is subject to peptide hydrolysis during the passage of the hepato-biliary system and is mainly excreted as peptide fragments in the feces. No quantitatively significant metabolites were detected in plasma samples after subcutaneous administration. In vitro studies have shown that degarelix is not a substrate, inducer or inhibitor of the CYP450 or p-glycoprotein transporter systems.

Excretion

Following subcutaneous administration of 240 mg Firmagon at a concentration of 40 mg/mL to prostate cancer patients, degarelix is eliminated in a biphasic fashion, with a median terminal half-life of approximately 53 days. The long half-life after subcutaneous administration is a consequence of a very slow release of degarelix from the Firmagon depot formed at the injection site(s).  Approximately 20-30% of a given dose of degarelix was renally excreted, suggesting that approximately 70-80% is excreted via the hepato-biliary system in humans. Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.

Effect of Age, Weight and Race

There was no effect of age, weight, or race on the degarelix pharmacokinetic parameters or testosterone concentration.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Degarelix was administered subcutaneously to rats every 2 weeks for 2 years at doses of 2, 10 and 25 mg/kg (about 9, 45 and 120% of the recommended human loading dose on a mg/m2 basis). Long term treatment with degarelix at 25 mg/kg caused an increase in the combined incidence of benign hemangiomas plus malignant hemangiosarcomas in females.

Degarelix was administered subcutaneously to mice every 2 weeks for 2 years at doses of 2, 10 and 50 mg/kg (about 5, 22 and 120% of the recommended human loading dose [240 mg] on a mg/m2 basis). There was no statistically significant increase in tumor incidence associated with this treatment.

Degarelix did not cause genetic damage in standard in vitro assays (bacterial mutation, human lymphocyte chromosome aberration) nor in in vivo rodent bone marrow micronucleus tests.

Single degarelix doses of ≥ 1 mg/kg (about 5% of the clinical loading dose on a mg/m2 basis) caused reversible infertility in male rats.  Single doses of ≥ 0.1 mg/kg (about 0.5% of the clinical loading dose on a mg/m2 basis) caused a decrease in fertility in female rats.

Clinical Studies

The safety and efficacy of Firmagon were evaluated in an open-label, multi-center, randomized, parallel-group study in patients with prostate cancer.  A total of 620 patients were randomized to receive one of two Firmagon dosing regimens or leuprolide for one year:

1. 
   

   Firmagon at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 160 mg (40 mg/mL) subcutaneously,

   
   


2. 
   

   Firmagon at a starting dose of 240 mg (40 mg/mL) followed by monthly doses of 80 mg (20 mg/mL) subcutaneously,

   
   


3. 
   

   leuprolide 7.5 mg intramuscularly monthly.

   
   

Serum levels of testosterone were measured at screening, on Day 0, 1, 3, 7, 14, and 28 in the first month, and then monthly until the end of the study.

The clinical trial population (n=610) across all treatment arms had an overall median age of approximately 73 (range 50 to 98).  The ethnic/racial distribution was 84% white, 6% black, and 10% others.  Disease stage was distributed approximately as follows:  20% metastatic, 29% locally advanced (T3/T4 Nx M0 or N1 M0), 31% localized (T1 or T2 N0 M0), and 20% classified as other (including patients whose disease metastatic status could not be determined definitively - or patients with PSA relapse after primary curative therapy).  In addition, the median testosterone baseline value across treatment arms was approximately 400 ng/dL.

The primary objective was to demonstrate that Firmagon is effective with respect to achieving and maintaining testosterone suppression to castration levels (T ≤ 50 ng/dL), during 12 months treatment.  The results are shown in Table 2.

Table 2: Medical Castration Rates (Testosterone ≤50 ng/dL) from Day 28 to Day 364

	Firmagon 240/160 mg N=202	Firmagon 240/80 mg N=207	Leuprolide 7.5 mg N=201
No. of Responders	199	202	194
Castration Rate (95% CIs)*	98.3% (94.8; 99.4)	97.2% (93.5; 98.8)	96.4% (92.5; 98.2)

* Kaplan Meier estimates within group

Percentage changes in testosterone from baseline to Day 28 (median with interquartile ranges) are shown in Figure 2 and the percentages of patients who attained the medical castration of testosterone ≤ 50 ng/dL are summarized in Table 3.

Figure 2: Percentage Change in Testosterone from Baseline by Treatment Group until Day 28 (Median with Interquartile Ranges)

Table 3: Percentage of Patients Attaining Testosterone ≤50 ng/dL within the First 28 Days

	Firmagon (240/160 mg) N=202	Firmagon (240/80 mg) N=207	Leuprolide (7.5 mg) N=201
Day 1	44%	52%	0%
Day 3	96%	96%	0%
Day 7	99%	99%	1%
Day 14	99%	99%	18%
Day 28	99%	100%	100%

In the clinical trial, PSA levels were monitored as a secondary endpoint. PSA levels were lowered by 64% two weeks after administration of Firmagon, 85% after one month, 95% after three months, and remained suppressed throughout the one year of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied.  No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.

REFERENCES

1. 
   

   NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

   
   


2. 
   

   OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

   
   


3. 
   

   American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006; 63:1172-1193.

   
   


4. 
   

   Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.). Pittsburgh, PA: Oncology Nursing Society.

   
   

HOW SUPPLIED-STORAGE AND HANDLING

Firmagon is available as:

• 
  

  NDC 55566-8401-1, Starting dose – One carton contains:
  
  Two vials each with 120 mg powder for injection

  
  


• 
  

  NDC 55566-8301-1, Maintenance dose – One carton contains:
  
  One vial with 80 mg powder for injection

  
  

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Caution should be exercised in handling and preparing the solution of Firmagon. Several guidelines on proper handling and disposal of anticancer drugs have been published.1-4  To minimize the risk of dermal exposure, always wear impervious gloves when handling Firmagon.  If Firmagon solution contacts the skin, immediately wash the skin thoroughly with soap and water. If Firmagon contacts mucous membranes, the membranes should be flushed immediately and thoroughly with water [see Contraindications (4) and Nonclinical Toxicology (13.1)].

Patient Counseling Information

(See FDA-approved Patient Labeling 17.2)

Information

• 
  

  Patients should be instructed to read the Patient Labeling carefully.

  
  


• 
  

  Patients should be informed of the possible side effects of androgen deprivation therapy, including hot flashes, flushing of the skin, increased weight, decreased sex drive, and difficulties with erectile function.  Possible side effects related to therapy with Firmagon include redness, swelling, and itching at the injection site; these are usually mild, self limiting, and decrease within three days.

  
  

FDA-approved Patient Labeling

Firmagon (FIRM-uh-gahn)

(degarelix for injection)

Read this patient information leaflet before you start taking Firmagon and each time you get a refill.There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is Firmagon?

Firmagon is a prescription medicine used in the treatment of advanced prostate cancer.

It is not known if Firmagon is safe or effective in children.

Who should not use Firmagon?

Firmagon should not be given to:

• 
  

  people who are allergic to any ingredient in Firmagon. See the end of this leaflet for a complete list of ingredients in Firmagon

  
  


• 
  

  women who are pregnant or may become pregnant

  
  

Talk to your healthcare provider before getting Firmagon if you have any of these conditions.

What should I tell my healthcare provider before receiving Firmagon?

Before receiving Firmagon, tell your healthcare provider about all your medical conditions, including if you:

• 
  

  have any heart problems

  
  


• 
  

  have problems with balance of your body salts or electrolytes, such as sodium, potassium, calcium, and magnesium

  
  


• 
  

  have kidney or liver problems

  
  


• 
  

  are breast-feeding or plan to breast-feed. It is not known if Firmagon passes into your breast milk. You and your healthcare provider should decide if you will take Firmagon or breast-feed. You should not do both without talking with your healthcare provider.

  
  

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking or have taken any medicines for your heart.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I receive Firmagon?

You will receive an injection of Firmagon from your healthcare provider.

• 
  

  The injection site will always be in the abdominal area but will change within that area with the next doses of Firmagon.

  
  


• 
  

  The injected medicine gives you a continuous release of Firmagon over one month.

  
  


• 
  

  Two injections are given as a first dose and the following monthly doses are one injection.

  
  


• 
  

  Make sure your injection site is free of any pressure from belts, waistbands or other types of clothing.

  
  


• 
  

  Always set up an appointment for your next injection.

  
  


• 
  

  If you miss a dose of Firmagon, or if you think you forgot to get your monthly dose of Firmagon, talk to your healthcare provider about how to get your next dose.

  
  

What are the possible side effects of Firmagon?

The common side effects include:

• 
  

  hot flashes

  
  


• 
  

  injection site pain, redness, and swelling, especially with the first dose

  
  


• 
  

  weight gain

  
  


• 
  

  increase in some liver enzymes

  
  


• 
  

  tiredness

  
  


• 
  

  hypertension

  
  


• 
  

  back and joint pain

  
  


• 
  

  chills

  
  


• 
  

  urinary tract infection

  
  


• 
  

  decreased sex drive and trouble with erectile function (impotence)

  
  

These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Firmagon.

Medicines are sometimes prescribed for conditions that are not mentioned in the patient leaflet. Do not use Firmagon for a condition for which it was not prescribed. Do not give Firmagon to other people, even if they have the same symptoms that you have. It may harm them.

This patient information leaflet summarizes the most important information about Firmagon. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Firmagon that is written for health professionals.

For more information, go to www.Firmagon.com or call 1-888-FERRING (1-888-337-7464).

What are the ingredients in Firmagon?

Active ingredient: degarelix (as acetate)

Inactive ingredient: mannitol

Manufactured for:

Ferring Pharmaceuticals Inc., Parsippany, NJ 07054

By: Rentschler Biotechnologie GmbH, Germany

6415-02

2/09

PACKAGE LABEL - 80 mg CARTON

NDC 5556-8301-1

Ferring Pharmaceuticals

Firmagon 80 mg

(degarelix for injection)

Rx only

For single use subcutaneous injection only

Treatment Maintenance (28 days)

PACKAGE LABEL - 240mg CARTON

NDC 55566-8401-01

Ferring Pharmaceuticals

Firmagon 240mg

(degarelix for injection)

*240 mg dose administered from two vials each containing 120 mg

For single use subcutaneous injection only

Treatment Initiation

PACKAGE LABEL - 80mg VIAL LABEL

2008051452

NDC 55566-8301-0

Rx only

Firmagon 80 mg

(degarelix for injection)

For subcutaneous injection only. Discard unused portion.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

Manufactured for: Ferring Pharmaceuticals Inc.,

Parsippany, NJ 07054

By: Rentschler Biotechnologie GmbH, Germany

6411-02

Ferring Pharmaceuticals

Lot No:

Exp:

PACKAGE LABEL - 120mg VIAL LABEL

2008051451

NDC 55566-8401-0

Rx only

Firmagon 120 mg

(degarelix for injection)

For subcutaneous injection only. Discard unused portion.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

Manufactured for: Ferring Pharmaceuticals Inc.,

Parsippany, NJ 07054

By: Rentschler Biotechnologie GmbH, Germany

6413-02

Ferring Pharmaceuticals

Lot No:

Exp:

Firmagon  degarelix  powder, metered

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 55566-8401 Route of Administration SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength degarelix acetate (degarelix) degarelix acetate 40 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength mannitol 150 mg  in 3 mL

Product Characteristics Color WHITE Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 55566-8401-1 2 VIAL In 1 CARTON contains a VIAL, GLASS (55566-8401-0) 1 55566-8401-0 3 mL In 1 VIAL, GLASS This package is contained within the CARTON (55566-8401-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA022201	03/02/2009

Firmagon  degarelix  powder, metered

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 55566-8301 Route of Administration SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength degarelix acetate (degarelix) degarelix acetate 20 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength mannitol 50 mg  in 1 mL

Product Characteristics Color WHITE Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 55566-8301-1 1 VIAL In 1 CARTON contains a VIAL, GLASS (55566-8301-0) 1 55566-8301-0 4 mL In 1 VIAL, GLASS This package is contained within the CARTON (55566-8301-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA022201	03/02/2009

Labeler - Ferring Pharmaceuticals Inc. (103722955)

Establishment
Name	Address	ID/FEI	Operations

Fondaparinux Sodium

Class: Direct Factor Xa Inhibitors
Chemical Name: MethylO - 2 - deoxy - 6 - O - sulfo - 2 - (sulfoamino) - α - d - glucopyranosyl - (1→4) - O - β - d - glucopyranuronosyl - (1→4) - O - 2 - deoxy - 3,6 - di - O - sulfo - 2 - (sulfoamino) - α - d - glucopyranosyl - (1→4) - O - 2 - O - sulfo - α - l - idopyranuronosyl - (1→4) - 2 - deoxy - 6 - O - sulfo - 2 - (sulfoamino) - α - d - glucopyranoside decasodium salt
Molecular Formula: C₃₁H₄₃N₃Na₁₀O₄₉S₈
CAS Number: 114870-03-0
Brands: Arixtra

• Spinal/Epidural Hematoma Risk


• 
  

  Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of fondaparinux, low molecular weight heparins, or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture.^{1 7 16 19}

  
  


• 
  

  Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet inhibitors, other anticoagulants).^{1 7 19}

  
  


• 
  

  Risk also increased by history of traumatic or repeated epidural or spinal puncture or history of spinal deformity or spinal surgery.^{1 3 4 7 19}

  
  


• 
  

  Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.^{1 7 19}

  
  


• 
  

  Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants.^{1 7 19} (See Neurologic Effects under Cautions and also see Interactions.)

  
  

Introduction

Anticoagulant; a synthetic activated factor X_a inhibitor.

Uses for Fondaparinux Sodium

Thromboprophylaxis in Hip-Fracture, Hip-Replacement, or Knee-Replacement Surgery

Prevention of postoperative DVT and PE in patients undergoing hip-fracture, hip-replacement, or knee-replacement surgery.^{1 2 3 4 5 6 10 19} The American College of Chest Physicians (ACCP) recommends fondaparinux, a low molecular weight heparin, or warfarin as first-line prophylaxis in such patients.¹⁹

Used for extended prophylaxis (i.e., approximately 3 weeks beyond the perioperative period) in patients undergoing hip-fracture surgery.^{1 18} ACCP recommends extended prophylaxis (e.g., up to 35 days) in patients undergoing total hip-replacement, total knee-replacement, or hip-fracture surgery who have ongoing risk factors for venous thromboembolism (e.g., history of venous thromboembolism, obesity, delayed mobilization, advanced age, cancer).¹⁹

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing general (e.g., abdominal) surgery who are at risk for thromboembolic complications, including those undergoing major surgical procedures or those undergoing general surgery with multiple risk factors for thromboembolism (e.g., history of previous venous thromboembolism, cancer, obesity, hypercoagulable state).^{1 19 26}

ACCP recommends a low molecular weight or unfractionated heparin or fondaparinux and/or intermittent pneumatic compression or graduated compression stockings for prevention of postoperative venous thromboembolism in patients at moderate or higher risk undergoing major general surgery, including abdominal, gynecologic†, and urologic surgery†, depending on the type of surgery and the risk for thromboembolism and bleeding.¹⁹

ACCP also recommends fondaparinux as an alternative to low molecular weight heparin or low-dose unfractionated heparin for thromboprophylaxis in patients undergoing extensive gynecologic surgery for malignancy, major open urologic procedures, inpatient bariatric surgery, or major thoracic surgery.¹⁹ Fondaparinux also recommended as an option for thromboprophylaxis in patients undergoing major vascular surgery, laparoscopic surgery, or gynecologic surgery who have additional risk factors for thromboembolism.¹⁹

Thromboprophylaxis in Selected Medical Conditions

ACCP recommends fondaparinux, low-dose unfractionated heparin, or low molecular weight heparin in acutely ill medical patients with heart failure, severe lung disease, or those confined to bedrest who have one or more additional risk factors (e.g., previous venous thromboembolism, sepsis, acute neurologic disease, inflammatory bowel disease).¹⁹

Treatment of DVT and PE

Used in conjunction with warfarin for treatment of DVT.^{1 20 22}

Used in conjunction with warfarin for treatment of PE, when initial therapy is given in the hospital.^{1 21 22} However, ACCP states that IV unfractionated heparin is preferred in patients experiencing massive PE; IV unfractionated heparin also preferred if there is concern about sub-Q absorption or in patients in whom thrombolytic therapy is being considered.²²

ST-Segment Elevation MI

Has been used as an adjunct to thrombolysis in a limited number of patients with acute ST-segment elevation MI†.^{25 29 32} The American College of Cardiology and American Heart Association (ACC/AHA) and ACCP recommend use of fondaparinux (given as an initial IV injection followed by daily sub-Q injections) in the management of such patients, except in those undergoing primary PCI.^{29 32 33}

Unstable Angina and Non-ST-Segment Elevation MI

Has been used as an alternative to unfractionated heparin or a low molecular weight heparin in the management of non-ST-segment elevation acute coronary syndromes† (unstable angina or non-ST-segment elevation MI)†.²⁸

ACCP recommends fondaparinux over enoxaparin in patients with non-ST-segment elevation acute coronary syndrome† undergoing early conservative or delayed invasive management.²⁸ ACC/AHA state that fondaparinux, unfractionated heparin, and enoxaparin are all acceptable options in patients with non-ST-segment elevation acute coronary syndrome being managed conservatively, but fondaparinux is preferred in patients with an increased risk of bleeding.³⁶

ACCP recommends unfractionated heparin and a GP IIb/IIIa-receptor inhibitor over fondaparinux in patients undergoing early invasive management.²⁸

Thrombosis Associated with Heparin-induced Thrombocytopenia

May be effective in the management of heparin-induced thrombocytopenia† (HIT).²⁷ However, ACCP states that other direct thrombin inhibitors such as lepirudin and argatroban are preferred as an alternative to unfractionated heparin in patients with confirmed or strongly suspected HIT†.²⁷

Fondaparinux Sodium Dosage and Administration

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 ST-segment elevation MI† or non-ST-segment elevation acute coronary syndromes†.^{28 29}

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 regular (unfractionated) heparin, heparinoids, or low molecular weight heparins cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis.¹ Differs from regular (unfractionated) heparin, heparinoids, or low molecular weight heparins 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

Hip-Fracture, Hip-Replacement, or Knee-Replacement Surgery

Prophylaxis of DVT and PE

Sub-Q

Patients weighing ≥50 kg: 2.5 mg once daily.^{1 19} Manufacturer recommends that initial dose be given no earlier than 6–8 hours after surgery, provided hemostasis has been established.¹ ACCP states that initial dose may be given either 6–8 hours after surgery or the next day following major orthopedic procedures.¹⁹ Avoid use in patients weighing <50 kg.¹ (See Contraindications.)

Usual duration of therapy is 5–9 days,^{1 3 4 5 6 7} although up to 11 days has been studied in clinical trials of orthopedic surgery.^{1 16}

Extended prophylaxis: Recommended for up to 24 additional days (i.e., after perioperative prophylaxis) in patients who have undergone hip-fracture or hip-replacement surgery; prophylaxis for up to a total of 32 days (including perioperative and extended prophylaxis) has been administered in clinical trials.^{1 18} ACCP states that extended prophylaxis (e.g., up to 35 days) should be considered in patients undergoing total hip-replacement, total knee-replacement, or hip-fracture surgery who have ongoing risk factors for venous thromboembolism (e.g., history of venous thromboembolism, obesity, delayed mobilization, advanced age, cancer).¹⁹

General Surgery

Prophylaxis of DVT and PE in Abdominal Surgery

Sub-Q

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 19 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

DVT and PE

Treatment

Sub-Q

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} however, ACCP recommends initiating warfarin simultaneously on the first day of fondaparinux treatment.²²

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 22}

ST-Segment Elevation MI†

IV, then Sub-Q

Initially, 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.^{29 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 (Cl_cr <30 mL/minute or S_cr ≥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.)

Cautions for Fondaparinux Sodium

Contraindications

• 
  

  Patients with severe renal impairment (Cl_cr <30 mL/minute or S_cr ≥3).^{1 32}

  
  


• 
  

  Prophylactic use in patients undergoing hip-fracture, hip-replacement, knee-replacement, or abdominal surgery who weigh <50 kg.¹

  
  


• 
  

  Active major bleeding, bacterial endocarditis, or thrombocytopenia associated with a positive in vitro test for antiplatelet antibody (heparin-induced thrombocytopenia) in the presence of the drug.^{1 3 4 10 16}

  
  

Warnings/Precautions

Warnings

Neurologic Effects

Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of fondaparinux and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.^{1 7 16} (See Boxed Warning.) Frequent monitoring for signs of neurologic impairment recommended.^{1 7} Some experts suggest that anticoagulant prophylaxis with fondaparinux be avoided in patients receiving epidural analgesia.^{3 4 7 19}

Hematologic Effects

Use with extreme caution in patients with an increased risk of hemorrhage (e.g., congenital or acquired bleeding disorders; active ulceration and angiodysplastic GI disease; hemorrhagic stroke; uncontrolled arterial hypertension; diabetic retinopathy; recent brain, spinal, or ophthalmic surgery).^{1 3 4} Use with caution in the treatment of DVT or PE in patients who weigh <50 kg.¹ Use with caution in patients with moderate renal insufficiency (Cl_cr 30–50 mL/minute).¹

Periodic routine blood counts, including platelet counts, and tests for occult blood in stool recommended.¹

Avoid concomitant use of drugs that increase risk of bleeding unless essential for management of underlying condition (e.g., concomitant use of vitamin K antagonists for treatment of venous thromboembolism).¹ Closely monitor for signs and symptoms of bleeding.¹

Do not administer earlier than 6–8 hours after surgery because of increased risk of major bleeding.¹

Moderate thrombocytopenia (platelet counts of 50,000–100,000/mm³) and severe thrombocytopenia (platelet counts <50,000/mm³) reported.¹ Fondaparinux unlikely to cause HIT;^{2 11 12 13} however, isolated cases of thrombocytopenia with thrombosis resembling HIT reported during postmarketing experience.¹ Manufacturer recommends monitoring thrombocytopenia of any degree closely and discontinuing fondaparinux if platelet counts fall below 100,000/mm³.¹ However, ACCP states that routine platelet count monitoring is not necessary due to the low frequency of HIT.²⁷

Patients with Prosthetic Heart Valves

Cases of valve thrombosis resulting in death and/or requiring surgical intervention reported with low molecular weight heparin (e.g., enoxaparin) therapy in patients with prosthetic heart valves; some cases included pregnant women, and maternal and/or fetal deaths have been reported.¹⁵ Manufacturer states that fondaparinux has not been studied in patients with prosthetic heart valves and that no information is available on safety of the drug in such patients.¹⁶

Sensitivity Reactions

Latex Sensitivity

Some packaging components (e.g., needle covers) contain natural latex proteins in the form of dry natural rubber (latex), which may cause allergic-type reactions (including life-threatening hypersensitivity reactions) in susceptible individuals.^{1 24 30 31} The needle cover of the diluent syringe should not be handled by individuals sensitive to latex.^{1 24 30 31}

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Use caution.¹

Pediatric Use

Safety and efficacy not established in children <17 years of age.^{1 16}

Geriatric Use

Use with caution.¹ No substantial differences in efficacy relative to younger adults.^{1 16} Possible increased major bleeding or other serious adverse effects in patients ≥75 years of age compared with younger adults.^{1 16} Substantially eliminated by kidneys; assess renal function periodically since geriatric patients are more likely to have decreased renal function.¹ Careful attention to dosage directions and concomitant therapy (particularly platelet-aggregation inhibitors) is advised.¹

Hepatic Impairment

Following a single 7.5 mg dose in patients with moderate hepatic impairment, response (i.e., aPTT, PT/INR, and antithrombin III) similar to that in patients with normal hepatic function.¹ Pharmacokinetics not studied in patients with severe hepatic impairment.¹

Increased risk of hemorrhage; closely monitor for signs and symptoms of bleeding.¹ (See Hematologic Effects under Cautions.)

Renal Impairment

Use with caution in those with moderate renal impairment (Cl_cr 30–50 mL/minute); increased risk of hemorrhage.^{1 16} Contraindicated in patients with severe renal impairment (Cl_cr <30 mL/minute or S_cr ≥3).^{1 16 32} Assess renal function periodically (e.g., serum creatinine determinations).¹ Discontinue immediately in patients who develop severe renal impairment during therapy.¹

Common Adverse Effects

Patients undergoing hip-fracture, hip- or knee-replacement surgery: Anemia, fever, nausea, edema, constipation, rash, vomiting, insomnia, increased wound drainage, hypokalemia, urinary tract infection, dizziness, purpura, hypotension, confusion, bullous eruption, urinary retention, hematoma, major bleeding, diarrhea, dyspepsia, postoperative hemorrhage, headache.^{1 16}

Patients undergoing abdominal surgery: Postoperative wound infection, postoperative hemorrhage, fever, surgical site reaction, anemia, hypertension, pneumonia, vomiting.¹

Venous thromboembolism: Constipation, headache, insomnia, fever, nausea, urinary tract infection, coughing.¹

Interactions for Fondaparinux Sodium

Weak inhibitor of CYP2A6, 1A2, 2C9, 2C19, 2D6, 3A4, and 3E1 in vitro.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.¹

Protein-bound Drugs

Pharmacokinetic interaction unlikely.¹

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Increased risk of bleeding1	Discontinue oral anticoagulants prior to initiation of fondaparinux1 If coadministration is essential, monitor patients closely1
Digoxin	Pharmacokinetic/pharmacodynamic interaction unlikely1 16
NSAIAs	Pharmacodynamic interaction unlikely1	Discontinue NSAIAs prior to initiation of fondaparinux1 If coadministration is essential, monitor patients closely
Platelet-aggregation inhibitors	Increased risk of bleeding1	Discontinue platelet-aggregation inhibitors prior to initiation of fondaparinux1 If coadministration is essential, monitor patients closely1

Fondaparinux Sodium Pharmacokinetics

Absorption

Bioavailability

Sub-Q: Absolute bioavailability 100%.^{1 10 b}

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 b}

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

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

Actions

• 
  

  Anticoagulation results from rapid inhibition of factor Xa by antithrombin III bound to fondaparinux (about 300-fold greater than innate activity).^{1 2 4 9 10} Neutralization of coagulation factor Xa inhibits the conversion of prothrombin to thrombin and subsequent thrombus formation.^{1 2 4 9 10} Unable to lyse established thrombi.¹⁶

  
  


• 
  

  Binds selectively to antithrombin III; unable to inactivate thrombin.^{1 2 4 8 9 16} At the recommended dosage, fibrinolytic activity not affected.¹

  
  


• 
  

  Platelet function or global clotting function tests (e.g., PT, bleeding time, aPTT) generally not affected when administered at the recommended dosage.^{1 10 16}

  
  

Advice to Patients

• 
  

  Importance of initiating self-administration only if a clinician determines that the such administration is appropriate and that medical follow-up is available as necessary.¹ Importance of appropriate training in injection technique.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Fondaparinux Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	2.5 mg/0.5 mL	Arixtra (available as a 0.5-mL, disposable prefilled syringe)	GlaxoSmithKline
		5 mg/0.4 mL	Arixtra (available as a 0.4-mL, disposable prefilled syringe)	GlaxoSmithKline
		7.5 mg/0.6 mL	Arixtra (available as a 0.6-mL, disposable prefilled syringe)	GlaxoSmithKline
		10 mg/0.8 mL	Arixtra (available as a 0.8-mL, disposable prefilled syringe)	GlaxoSmithKline

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 11, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. GlaxoSmithKline. Arixtra (fondaparinux sodium) injection prescribing information. Research Triangle Park, NC: 2010 Mar.

2. Turpie AGG, Gallus AS, Hoek JA, for the Pentasaccharide Investigators. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001; 344:619-25. [IDIS 459860] [PubMed 11228275]

3. Eriksson BI, Bauer KA, Lassen MR et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip- fracture surgery. N Engl J Med. 2001; 345:1298-304. [IDIS 471305] [PubMed 11794148]

4. Bauer KA, Eriksson BI, Lassen MR et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001; 345:1305-10. [IDIS 471306] [PubMed 11794149]

5. Lassen MR, Bauer KA, Eriksson BI et al. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: A randomized double-blind comparison.Lancet 2002; 359:715-20.

6. Turpie GG, Bauer KA, Eriksson BI et al.. Postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: A randomized double-blind trial. Lancet 2002; 359:1721-6. [IDIS 481278] [PubMed 12049860]

7. Geerts WH, Heit JA, Clagett GP et al. Prevention of venous thrombembolism. Chest. 2001; 119 (Suppl):133S-75S.

8. Hirsh J, Warkentin TE, Shaughnessy SG et al. Heparin and low- molecular-weigh heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest. 2001; 119:64S-94s. [IDIS 459443] [PubMed 11157643]

9. Weitz J, Hirsh J. New anticoagulant drugs. Chest. 2001; 119:95S- 107s. [IDIS 459444] [PubMed 11157644]

10. Bauer KA. Fondaparinux sodium: a selective inhibitor of factor Xa. Am J Health-Syst Pharm. 2001; 58 (Suppl.2):S14-7. [IDIS 472189] [PubMed 11715834]

11. Rosenberg RD. Redesigning heparin. N Engl J Med. 2001; 344:673-4. Editorial. [IDIS 459863] [PubMed 11228284]

12. Ahmad S, Jeske WP, Walenga JM et al. Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. Clin Appl Thromb Hemost. 1999; 5:259-66. [PubMed 10726024]

13. Amiral J, Lormeau JC, Marfaing-Koka A et al. Absence of cross- reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis. 1997; 8:114-7. [PubMed 9518042]

14. Hull R, Pineo G. A synthetic pentasaccharide for the prevention of deep- vein thrombosis. N Engl J Med. 2001; 345:291. Letter. [IDIS 467250] [PubMed 11474672]

15. Aventis. Lovenox (enoxaparin sodium) injection prescribing information. Bridgewater, NJ; 2001 Jul.

16. Organon Sanofi-Synthelabo, West Orange, NJ: Personal communication.

17. Bounameaux, H, Perneger T. Fondaparinux: A new synthetic pentasaccharide for thrombosis prevention. Lancet.2002; 359:1710-1.

18. Eriksson BI, Lassen MR. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2003; 163:1337-42. [IDIS 499798] [PubMed 12796070]

19. Geerts WH, Bergqvist D, Pineo GF et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133(Suppl.):381S-453S. [IDIS 523840] [PubMed 15383478]

20. Buller HR, Davidson BL, Decousus H et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004; 140:867-73. [IDIS 516440] [PubMed 15172900]

21. Buller HR, Davidson BL, Decousus H et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003; 349:1695-702. [IDIS 505897] [PubMed 14585937]

22. Kearon C, Kahn SR, Agnelli G et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008:133 (Suppl.):454S-545S.

23. Organon Sanofi-Synthelabo. Arixtra (fondaparinux sodium) injection prescribing information. West Orange, NJ: 2001 Dec.

24. Food and Drug Administration. Natural rubber-containing medical devices; user labeling. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1997; 62:51021-30.

25. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004; 44(3):671-719. [PubMed 15358045]

26. Agnelli G, Bergvist D, Cohen AT et al. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005; 92:1212-20. [PubMed 16175516]

27. Warkentin TE, Greinacher A, Koster A et al. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133:340S-80S [PubMed 18574270]

28. Harrington RA, Becker RC, Cannon CP et al. Antithrombotic therapy for non ST-segment elevation acute coronary syndromes: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008:133:670S-707S.

29. Goodman SG, Menon V, Cannon CP et al. Acute ST-segment elevation myocardial infarction: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133:708S-75S [PubMed 18574277]

30. Food and Drug Administration. Amended economic impact analysis of final rule requiring use of labeling on natural rubber containing devices. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1998; 63:50660-704.

31. Food and Drug Administration. Latex-containing devices; user labeling. 21 CFR Part 801. Proposed rule. (Docket No. 96N-0119) Fed Regist. 1996; 61:32617-21.

32. Antman EM, Anbe DT, Armstrong PW et al. 2007 Focused Update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction). J Am Coll Cardiol. 2008; 51:210–47.

33. King SB III, Smith SC Jr, Hirschfeld JW Jr et al. 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: American College of Cardiology/American Heart Association Task Force on Practice Guidelines, 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. JACC. 2008; 51:172-209. [PubMed 18191745]

34. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006; 354:1464-76. [PubMed 16537663]

35. Mehta SR, Granger CB, Eikelboom JW et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007; 50:1742-51. [PubMed 17964037]

36. Anderson JL, Adams CD, Antman EM et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007; 50:e1-e157. [PubMed 17692738]

b. Donat F, Duret JP, Santoni A et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 2002; 41 Suppl 2:1-9. [PubMed 12383039]

More Fondaparinux Sodium resources

• Fondaparinux Sodium Side Effects (in more detail)
• Fondaparinux Sodium Use in Pregnancy & Breastfeeding
• Fondaparinux Sodium Drug Interactions
• Fondaparinux Sodium Support Group
• 3 Reviews for Fondaparinux Sodium - Add your own review/rating

• Arixtra Prescribing Information (FDA)


• Arixtra Concise Consumer Information (Cerner Multum)


• Arixtra Advanced Consumer (Micromedex) - Includes Dosage Information


• Arixtra MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Fondaparinux Sodium with other medications

• Deep Vein Thrombosis
• Deep Vein Thrombosis Prophylaxis after Abdominal Surgery
• Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery
• Deep Vein Thrombosis Prophylaxis after Knee Replacement Surgery
• Deep Vein Thrombosis, Prophylaxis
• Pulmonary Embolism