Azathioprine

Azathioprine

Definition

Azathioprine is a non-specific immunosuppressant antimetabolite that can be used as a chemotherapeutic agent to inhibit lymphocyte purine metabolism. In the United States, azathioprine is also known by the brand name Imuran.

Purpose

In 1968 the Food and Drug Administration approved azathioprine for use after an organ transplant to decrease the chance of the body rejecting the transplanted organ. However, azathioprine is an experimental drug that can be used during treatment of cancers such as leukemia and lymphomas. In the body, azathioprine is converted to mercaptopurine (6-MP) and thus has the same effects as that chemotherapy drug. They both are purine analogs that interfere with the metabolism of purine-based nucleotides found in DNA.

The use of azathioprine results in killing cells such as T-lymphocytes. This is important in cancers such as lymphocytic leukemia. The idea is that if T-lymphocyte reproduction is inhibited by interfering with DNA synthesis, then the cancer cell reproduction will also be inhibited. Certain types of leukemia and lymphomas are treated with radiation and chemotherapy, which destroy dividing cells such as those in the bone marrow. As a result, the patient is no longer able to produce blood cells. To combat the loss of blood cells, a bone marrow transplant may be performed to provide the patient with healthy marrow. The body may react against the foreign bone marrow. Therefore, an additional benefit of azathioprine use as an immunosuppressant could be to produce fewer white blood cells, thus interfering with the body's natural immune response to foreign proteins, such as those found on the cell surfaces of bone marrow coming from a bone marrow donor.

Description

Azathioprine is a derivative of mercaptopurine, a purine analog antimetabolite, which interferes with the enzymatic pathways for biosynthesis of nucleic acids by substituting for normal metabolites. In this way, it can act as an immunosuppressant by interfering with the production of white blood cells such as lymphocytes.

Recommended dosage

Azathioprine can be taken either orally (50 milligram scored tablets) or through an injection (100 milligram vials for intravenous use). Dosing is based on body weight and size of the patient. Initially, the oral dosage is approximately 3 to 5 milligrams per kilogram of body weight, while the injection dosage is approximately 1 milligram per kilogram of body weight. At time goes on, the physician may decrease the dosage. Patients can take this medicine in a single dose per day. The duration of treatment will continue until the fear of transplant rejection has passed.

Precautions

Since this medication is an immunosuppressant and results in a lower white blood cell count, there is a higher risk of developing infection. Therefore, patients using azathioprine should limit their contact with people that have existing infections, they should not have dental work done while on this medication, and they should not touch their eyes or inside of their nose unless they have just washed their hands. Patients should also take care not to cut themselves and should be careful when using a regular toothbrush and dental floss.

Pregnant women should not take this drug since it can cross the placenta and can have serious side effects. Women who are breastfeeding should not take this drug. Azathioprine can pass through the breast milk to the baby and can result in serious problems.

Side effects

The most common and less serious side effects include fatigue , weakness, loss of appetite (anorexia ), nausea and vomiting , and upset stomach. Upset stomach can be alleviated if azathioprine is taken with food or milk.

Other side effects may occur that require the attention of a medical professional. These include:

• cough or hoarseness
• fever or chills
• lower back or side pain
• extreme fatigue
• black tarry stools
• blood in the urine
• red spots on the skin
• fast heartbeat
• shortness of breath
• liver problems

Since the immune system is depressed when azathioprine is used, the result can be pancytopenia, including leukopenia and thrombocytopenia as well as macro-cytic anemia . The severity of these is dependent on the dose, and the dose may be lowered by the physician as needed.

Azathioprine has been used in children and has not been shown to induce side effects different than those found in adults. However, as with many medications there have not been any specific tests done with the elderly. It is not expected to cause any different side effects than those encountered in younger adults.

Interactions

There are medications and other medical conditions that can interact with azathioprine. A medication called allopurinol is used to treat gout and can increase the effects and toxicity of azathioprine because it interferes with the removal of azathioprine from the body.

Both kidney disease and liver disease can increase the effects and toxicity of azathioprine. Both diseases interfere with the removal of azathioprine from the body. If the patient has either of these diseases, the physician may make adjustments in the dosage given.

Sally C. McFarlane-Parrott

KEY TERMS

Analog

—A chemical compound with a structure similar to another chemical, but differing in a certain way.

Antimetabolite

—A drug that resembles a substance that occurs naturally in a metabolic pathway, interfering with metabolism.

Bone marrow

—The soft tissue inside of bones that produces blood cells.

Gout

—A form of arthritis that involves ureic acid.

Leukopenia

—Decrease in the amount of white blood cells.

Lymphocytes

—A type of white blood cell and part of the immune system.

Macrocytic anemia

—Anemia where blood cells are much larger than normal.

Myelosuppression

—Decrease in the proliferation of bone marrow cells.

Pancytopenia

—Decrease in all the cellular components of the blood.

Purine

—A base found in nucleotides and nucleic acids that are used to make DNA.