Abarelix

Key Terms: Antagonist, Cryoablation, Osteoporosis, Pituitary gland, Testes.

Definition

Abarelix is an injectable gonadotrophin-releasing hormone (GnRH) antagonist that is used to decrease the production of the male hormone testosterone.

Purpose

Abarelix is used in men to treat advanced prostate cancer that has not responded to other treatments or when other treatments have been refused. The prostate gland lies under the bladder and surrounds the urethra. Its main function is to produce seminal fluid that mixes with sperm prior to ejaculation. Prostate cancer is the most common cancer in men over the age of 50.

Other treatments for prostate cancer should be tried before treatment with abarelix is prescribed. Early stage prostate cancer is often treated with surgery or radiation therapy and less often with cryoablation. Advanced stage prostate cancer may be treated with other drugs that decrease the production of testosterone. Another approach to treating advanced prostate cancer is surgical removal of the testicles (castration). Some men reject this surgery, making them candidates for treatment with abarelix.

Because abarelix can cause serious side effects, this drug is considered appropriate for use only in the following situations:

• The cancer has spread (metastasized) and is close to the spinal column, so that there is a risk that pressure will cause damage to the spinal nerves.
• The urethra or bladder is blocked because of malignant tissue growth making urination difficult or impossible.
• Prostate cancer causes severe pain in the bones that narcotic pain medication cannot control.

Description

Abarelix works by blocking gonadotropin-releasing hormone (GRH) a hormone released from the anterior pituitary gland that stimulates the production of testosterone. When this messenger hormone from the pituitary is blocked, the level of testosterone in the blood decreases. Prostate cancer cells grow best in the presence of testosterone, so by decreasing the amount available, growth of the tumor is slowed or stopped. Other drugs (leuprolide acetate [Lupron], goserelin acetate [Zoladex]) are available that also decrease testosterone production. One advantage of abarelix over these other drugs is that the other drugs used to decrease testosterone levels first stimulate the production of testosterone then decrease it. With abarelix, there is no initial increase in testosterone production and decline in production of the hormone begins immediately. However, abarelix may stop working in some men after an initial period of effectiveness. The drug does not cure prostate cancer but can relieve symptoms.

Abarelix is manufactured in the United States by Praecis Pharmaceuticals and sold under the brand name Plenaxis. Generic substitutes are not available, and as of 2005 there is only one American manufacturer. Abarelix was approved for use by the United States Food and Drug Administration (FDA) in December 2003 with restrictions. The drug can only be administered by doctors who are registered in the Plenaxis PLUS Program (Plenaxis User Safety Program) because of its potentially life-threatening side effects.

Recommended Dosage

Abarelix is an injectable liquid. It is supplied as powder in single dose vial to which the physician adds a small amount of saline (saltwater) before use. The resulting liquid is injected into the buttocks muscle. The treatment cycle calls for an initial injection on days 1, 15, and 29 followed by an injection every 28 days. The testosterone level of the blood should be checked after the first month and then about every eight weeks to assure that the drug is continuing to work. Liver function tests should also be done regularly, as abarelix may cause changes in the liver function. These changes are usually not permanent and go away once the drug is stopped.

Precautions

Certain individuals should not use abarelix. These include women, children under age 18, and men with a rare heart condition called prolongation of the QTc interval. Men with osteoporosis, liver disease, and blood clotting disorders should identify these existing problems to their doctor before beginning treatment. Abarelix may stop working in some men and is more likely to stop working in men weighing over 225 lb (102 kg). There are no special dietary restriction when receiving abarelix therapy.

Side Effects

Abarelix can cause serious or life-threatening allergic reactions either during or after administration. Therefore, the drug can only be administered by a physician registered in the Plenaxis PLUS safety program. The likelihood of life-threatening reactions increases with each injection of abarelix. For this reason, men receiving an injection of abarelix must remain under observation in the doctor's office for at least 30 minutes following each treatment.

Symptoms of rare but life-threatening reactions include:

• low blood pressure, fainting, shock
• swelling of the face, eyelids, tongue, or throat
• wheezing, asthma, tightness in the chest, difficulty breathing

More common but less serious side effects include:

• hot flashes
• rapid heart beat (tachycardia)
• rash, hives, itching, skin redness
• vomiting
• jaundice (yellowing of the whites of the eyes or skin)
• stomach pain
• breast enlargement
• problems sleeping
• breast, back or other pain
• constipation
• changes in the electrical profile of the heart

Interactions

It is important for patients to discuss with their physician all prescription medications, over-the-counter medications, and herbal or alternative remedies that the patients are taking before treatment with abarelix is begun. Although as of 2005 formal drug interaction studies have not been completed, a number of drugs may interact with abarelix. These include:

• arsenic trioxide
• astemizole (Hismanal)
• bepridil (Vascor)
• certain antibiotics
• cisapride (Propulsid)
• cyclobenzaprine (Flexeril)
• DHEA (dietary supplement)
• dolasetron (Anzemet)
• droperidol
• halofantrine (Halfan)
• estrogen or other female hormones
• levomethadyl (Orlaam)
• medications that regulate heart rhythm
• medications that treat depression
• palonosetron (Aloxi)
• pentamidine (Pentam)
• phenothiazines (found in antihistamines)
• pimozide (Orap)
• probucol (Lorelco)

—Tish Davidson, A. M.