Fondaparinux

Fondaparinux has the brand name Arixtra. It is an anticoagulant. Anticoagulants prevent blood from clotting. The Food and Drug Administration approved the use of fondaparinux in December, 2001. In 2007, fondaparinux became the first synthetic anticoagulant to receive approval for the prevention of deep vein thrombosis in patients undergoing hip fracture surgery, hip replacement surgery or knee replacement surgery. The first drug in a new class of agents that inhibit Factor Xa, fondaparinux was discovered by Sanofi-Synthelabo in conjunction with Akzo Nobel subsidiary Organon Pharmaceuticals. Now Fondaparinux is marketed by Fonda BV. Over time, the manufacturers of fondaparinux were successful in extending the scope of approved uses to include abdominal surgery and further indications for the prevention in hip fracture surgery. Other innovative aspects of the drug include the ability to dose once daily, convenience of home use, and no extensive blood level monitoring.

Uses/Indications

Fondaparinux is used to reduce the risk of blood clotsin the deep veins of the legs and thighs. These clots may break off and travel to the lungs (pulmonary embolism). Patients at risk for these complications include those undergoing the following:

• hip fracture surgery
• hip replacement surgery
• knee replacement surgery
• abdominal surgery who are already at risk of blood clot complications

Fondaparinux is also used with warfarin to treat the following:

• blood clots in the veins
• blood clots that have broken off and traveled to the lungs (pulmonary embolism) *the risk of blood clots during the initial treatment in the hospital

How Fondaparinux is Taken

Fondaparinux is administered as a subcutaneous (under the skin) injection. It is available at concentrations of 2.5 mg / 0.5 ml, 5 mg / 0.4 ml, 7.5 mg / 0.6 ml, and 10 mg / 0.8 ml. The injection is taken once a day, and the dose is adjusted according to weight: 5 mg for weights less than 110 lbs (50 kg), 7.5 mg for weights 110–220 lbs (50-100 kg), and 10 mg for weights greater than 220 lbs(100 kg).

Routine laboratory tests are used to monitor safety. These tests include a complete blood count (CBC) that measures the amount of cells in the blood, test of kidney function, and a test for the presence of blood in the stool.

How Fondaparinux Works

Fondaparinux inhibits Factor Xa (an enzyme used in the body's clotting mechanism). Fondaparinux is the only drug available that works in this manner.

How the Body Affects Fondaparinux

Peak plasma concentrations of fondaparinux are reached approximately two hours after injection of any dose. Fondaparinux is largely excreted unchanged in the urine. The body does not alter (metabolize) fondaparinux to a large extent. The half-life, or time needed for the concentration of the drug in the body to be reduced by half, is 17-21 hours.

In special populations

The elimination of fondaparinux from the body is reduced in persons with kidney damage because the drug is primarily excreted in the urine. The clearance of fondaparinux from the body is reduced by approximately 25%, 40%, and 55% in patients with mild, moderate, and severe kidney impairment, respectively. ^[1]

Age and weight also affect the elimination of fondaparinux.^[1] Elimination of fondaparinux is approximately 25% slower in patients over the age of 75 years compared to patients 65 years old or younger. In patients under 110 lbs, fondapairnux is eliminated approximately 30% slower than in patients over 110 pounds.

Side Effects

Below are some commonly encountered side effects of fondaparinux:

• minor bleeding, rash, or itching at the injection site
• fever
• insomnia
• constipation
• nausea or vomiting
• swelling or water retention

Fondaparinux use is also associated with more serious side effects:

• Allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives)
• prolonged or unexplained bleeding
• pain, warmth, or redness in an arm or leg, or difficulty breathing, which could indicate a blood clot
• excessive bruising or paleness
• black, bloody, or tarry stools
• blood in the urine
• sudden severe headache
• sudden severe stomach pain
• ulceration (open wound) at injection site.

Risks and Precautions

Fondaparinux and other medicines like it can cause bleeding into the spine when used in patients who have received epidural or spinal anesthesia, or any spinal injection. Bleeding in the spine can cause long term or permanent paralysis. The risk of this complication is increased in patients receiving blood thinners, acetylsalicylic acid (Aspirin), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin) or naproxen (Naprosyn or Aleve).

Fondaparinux is given with extreme caution to people who have conditions that increase the risk of excessive bleeding. These conditions include the following:

• bleeding disorders or recent bleeding episodes
• ulcerative colitis and other bleeding disorders in the stomach and intestines
• bleeding into the brain (hemorrhagic stroke)
• recent brain, spinal, or eye surgery
• Use of other anticoagulants
• recent stomach ulcer

Caution is also used in patients with uncontrolled high blood pressure (hypertension), eye problems due to diabetes, and stroke.

Contraindications

Fondaparinux is not generally used in patients under 110 lbs, or who have severe kidney problems. The elimination of fondaparinux from the body is reduced in these patients (see “How the Body Affects fondaparinux”).

Accordingly, the drug may accumulate in these patients. Because fondaparinux prevents blood clotting, its use in patients with bleeding is avoided. Below are some other conditions during which fondaparinux is not used:

• heart infection (bacterial endocarditis)
• history of fondaparinux-induced low platelet number (thrombocytopenia)
• allergy to fondaparinux or to any of the ingredients in Arixtra

Research

• A meta-analysis (analysis of several studies) performed in March 2008 showed strong evidence that warfarin, heparin and aspirin slow down fracture healing, whereas fondaparinux did not impair healing in non-human lab tests.^[2]

• A 2008 study comparing the efficacy and tolerability of enoxaparin (brand Lovenox) and fondaparinux showed equal efficacy in the treatment of patients with unstable angina (chest pain) or non-ST elevation myocardial infarction (NSTEMI, a type of heart attack) and that fondaparinux was more effective than usual care in those with heart attack. Fondaparinux also was shown to have a favorable tolerability profile, particularly with regard to the risk of major bleeding. The study also suggested that fondaparinux is more cost-effective than enoxaparin in the short term.^[3]

Sales

Sales of fondaparinux were U.S. $190 million in 2007.^[4] The sales were a disappointment considering the high cost and low yield of fondaparinux synthesis.

References

1. ↑ ^{1.0 1.1} Arixtra. Arixtra Prescribing Information. Accessed May 11, 2008
2. ↑ Lindner T, Cockbain AJ, El Masry MA, Katonis P, Tsiridis E, Schizas C, Tsiridis E. The effect of anticoagulant pharmacotherapy on fracture healing. Abstract. Expert Opin Pharmacother. 2008 May;9(7):1169-87.
3. ↑ Blick SK, Orman JS, Wagstaff AJ, Scott LJ. Fondaparinux sodium: a review of its use in the management of acute coronary syndromes. Abstract. Am J Cardiovasc Drugs. 2008;8(2):113-25.
4. ↑ Wall Street Online. Alchemia.. Accessed May 12, 2008.

External Links

Official Arixtra Website

Arixtra Consumer Information Sheet

Arixtra Drug Monograph from RxList.com