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Related to immunosuppressant drugs: cyclosporine, azathioprine
Immunosuppressant drugs, also called anti-rejection drugs, are used to prevent the body from rejecting a transplanted organ.
When an organ, such as a liver, a heart or a kidney, is transplanted from one person (the donor) into another (the recipient), the immune system of the recipient triggers the same response against the new organ it would have to any foreign material, setting off a chain of events that can damage the transplanted organ. This process is called rejection and it can occur rapidly (acute rejection), or over a long period of time (chronic rejection). Rejection can occur despite close matching of the donated organ and the transplant patient. Immunosuppressant drugs greatly decrease the risks of rejection, protecting the new organ and preserving its function. These drugs act by blocking the immune system so that it is less likely to react against the transplanted organ. A wide variety of drugs are available to achieve this aim but work in different ways to reduce the risk of rejection.
In addition to being used to prevent organ rejection, immunosuppressant drugs are also used to treat such severe skin disorders as psoriasis and such other diseases as rheumatoid arthritis, Crohn's disease (chronic inflammation of the digestive tract) and patchy hair loss (alopecia areata). Some of these conditions are termed "autoimmune" diseases, indicating that the immune system is acting against the body itself.
Immunosuppressant drugs can be classified according to their specific molecular mode of action. The three main immunosuppressant drugs currently used in organ transplantations are the following:
- Cyclosporins (Neoral, Sandimmune, SangCya). These drugs act by inhibiting T-cell activation, thus preventing T-cells from attacking the transplanted organ.
- Azathioprines (Imuran). These drugs disrupt the synthesis of DNA and RNA and cell division.
- Corticosteroids such as prednisolone (Deltasone, Orasone). These drugs suppress the inflammation associated with transplant rejection.
Most patients are prescribed a combination of drugs after their transplant, one from each of the above main groups; for example cyclosporin, azathioprine and prednisolone. Over a period of time, the doses of each drug and the number of drugs taken may be reduced as the risks of rejection decrease. However, most patients need to take at least one immunosuppressive for the rest of their lives.
Immunosuppressants can also be classified depending on the specific transplant:
- basiliximab (Simulect) is also used in combination with such other drugs as cyclosporin and corticosteroids, in kidney transplants
- daclizumab (Zenapax) is also used in combination with such other drugs as cyclosporin and corticosteroids, in kidney transplants
- muromonab CD3 (Orthoclone OKT3) is used, along with cyclosporin, in kidney, liver and heart transplants
- tacrolimus (Prograf) is used in liver transplants and is under study for kidney, bone marrow, heart, pancreas, pancreatic island cell, and small bowel transplantation
Some immunosuppressants are also used to treat a variety of autoimmune diseases:
- Azathioprine (Imuran) is used not only to prevent organ rejection in kidney transplants, but also in treatment of rheumatoid arthritis. It has been used to treat chronic ulcerative colitis, but it has been of limited value for this use.
- Cyclosporin (Sandimmune, Neoral) is used in heart, liver, kidney, pancreas, bone marrow and heart/lung transplantation. The Neoral form has been used to treat psoriasis and rheumatoid arthritis. The drug has also been used for many other conditions including multiple sclerosis, diabetes and myesthenia gravis.
- Glatiramer acetate (Copaxone) is used in treatment of relapsing-remitting multiple sclerosis. In one study, glatiramer reduced the frequency of multiple sclerosis attacks by 75% over a two-year period.
- Mycopehnolate (CellCept) is used along with cyclosporin in kidney, liver and heart transplants. It has also been used to prevent the kidney problems associated with lupus erythematosus.
- Sirolimus (Rapamune) is used in combination with other drugs including cyclosporin and corticosteroids, in kidney transplants. The drug is also used for the treatment of psoriasis.
Immunosuppressant drugs are available only with a physician's prescription. They come in tablet, capsule, liquid and injectable forms.
The recommended dosage depends on the type and form of immunosuppressant drug and the purpose for which it is being used. Doses may be different for different patients. The prescribing physician or the pharmacist who filled the prescription will advise on correct dosage.
Taking immunosuppressant drugs exactly as directed is very important. Smaller, larger or more frequent doses should never be taken, and the drugs should never be taken for longer than directed. The physician will decide exactly how much of the medicine each patient needs. Blood tests often are necessary to monitor the action of the drug.
The prescribing physician should be consulted before stopping an immunosuppressant drug.
Seeing a physician regularly while taking immunosuppressant drugs is important. These regular checkups will allow the physician to make sure the drug is working as it should and to watch for unwanted side effects. These drugs are very powerful and can cause serious side effects, such as high blood pressure, kidney problems and liver problems. Some side effects may not show up until years after the medicine is used. Anyone who has been advised to take immunosuppressant drugs should thoroughly discuss the risks and benefits with the prescribing physician
Immunosuppressant drugs lower a person's resistance to infection and can make infections harder to treat. The drugs can also increase the chance of uncontrolled bleeding. Anyone who has a serious infection or injury while taking immunosuppressant drugs should get prompt medical attention and should make sure that the treating physician knows about the immunosuppressant prescription. The prescribing physician should be immediately informed if signs of infection, such as fever or chills, cough or hoarseness, pain in the lower back or side, or painful or difficult urination, bruising or bleeding, blood in the urine, bloody or black, tarry stools occur. Other ways of preventing infection and injury include washing the hands frequently, avoiding sports in which injuries may occur, and being careful when using knives, razors, fingernail clippers or other sharp objects. Avoiding contact with people who have infections is also important. In addition, people who are taking or have been taking immunosuppressant drugs should not have immunizations, such as smallpox vaccinations, without checking with their physicians. Because of their low resistance to infection, people taking these drugs might get the disease that the vaccine is designed to prevent. People taking immunosuppressant drugs also should avoid contact with anyone who has taken the oral polio vaccine, as there is a chance the virus could be passed on to them. Other people living in their home should not take the oral polio vaccine.
Immunosuppressant drugs may cause the gums to become tender and swollen or to bleed. If this happens, a physician or dentist should be notified. Regular brushing, flossing, cleaning and gum massage may help prevent this problem. A dentist can provide advice on how to clean the teeth and mouth without causing injury.
People who have certain medical conditions or who are taking certain other medicines may have problems if they take immunosuppressant drugs. Before taking these drugs, the prescribing physician should be informed about any of these conditions:
ALLERGIES. Anyone who has had unusual reactions to immunosuppressant drugs in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.
PREGNANCY. Azathioprine may cause birth defects if used during pregnancy, or if either the male or female is using it at time of conception. Anyone taking this medicine should use a barrier method of birth control, such as a diaphragm or condoms. Birth control pills should not be used without a physician's approval. Women who become pregnant while taking this medicine should check with their physicians immediately.
The medicine's effects have not been studied in humans during pregnancy. Women who are pregnant or who may become pregnant and who need to take this medicine should check with their physicians.
BREASTFEEDING. Immunosuppressant drugs pass into breast milk and may cause problems in nursing babies whose mothers take it. Breastfeeding is not recommended for women taking this medicine.
OTHER MEDICAL CONDITIONS. People who have certain medical conditions may have problems if they take immunosuppressant drugs. For example:
- People who have shingles (herpes zoster) or chickenpox, or who have recently been exposed to chickenpox, may develop severe disease in other parts of their bodies when they take these medicines.
- The medicine's effects may be greater in people with kidney disease or liver disease, because their bodies are slow to get rid of the medicine.
- The effects of oral forms of this medicine may be weakened in people with intestinal problems, because the medicine cannot be absorbed into the body.
Before using immunosuppressant drugs, people with these or other medical problems should make sure their physicians are aware of their conditions.
USE OF CERTAIN MEDICINES. Taking immunosuppressant drugs with certain other drugs may affect the way the drugs work or may increase the chance of side effects.
Increased risk of infection is a common side effect of all the immunosuppressant drugs. The immune system protects the body from infections and when the immune system is suppressed, infections are more likely. Taking such antibiotics as co-trimoxazole prevents some of these infections. Immunosuppressant drugs are also associated with a slightly increased risk of cancer because the immune system also plays a role in protecting the body against some forms of cancer. For example, long-term use of immunosuppressant drugs carries an increased risk of developing skin cancer as a result of the combination of the drugs and exposure to sunlight.
Other side effects of immunosuppressant drugs are minor and usually go away as the body adjusts to the medicine. These include loss of appetite, nausea or vomiting, increased hair growth, and trembling or shaking of the hands. Medical attention is not necessary unless these side effects continue or cause problems.
The treating physician should be notified immediately if any of the following side effects occur:
- unusual tiredness or weakness
- fever or chills
- frequent need to urinate
Antibody — Protein produced by the immune system in response to the presence in the body of an antigen.
Antigen — Any substance or organism that is foreign to the body. Examples of antigens are: bacteria, bacterial toxins, viruses, or other cells or proteins.
Autoimmune disease — A disease in which the immune system is overactive and has lost the ability to distinguish between self and non-self.
Chronic — A word used to describe a long-lasting condition. Chronic conditions often develop gradually and involve slow changes.
Corticosteroids — A class of drugs that are synthetic versions of the cortisone produced by the body. They rank among the most powerful anti-inflammatory agents.
Cortisone — Glucocorticoid produced by the adrenal cortex in response to stress. Cortisone is a steroid with anti-inflammatory and immunosuppressive properties.
Immune response — Physiological response of the body controlled by the immune system that involves the production of antibodies to fight off specific foreign substances or agents (antigens).
Immune system — The network of organs, cells, and molecules that work together to defend the body from foreign substances and organisms causing infection and disease such as: bacteria, viruses, fungi and parasites.
Immunosuppresive cytotoxic drugs — A class of drugs that function by destroying cells and suppressing the immune response.
Immunosuppressant — Any chemical substance that suppresses the immune response.
Immunosuppressive — Any agent that suppresses the immune response of an individual.
Inflammation — A process occurring in body tissues, characterized by increased circulation and the accumulation of white blood cells. Inflammation also occurs in such disorders as arthritis and causes harmful effects.
Inflammatory — Pertaining to inflammation.
Lymphocyte — Lymphocytes are white blood cells that participate in the immune response. The two main groups are the B cells that have antibody molecules on their surface and T cells that destroy antigens.
Psoriasis — A skin disease characterized by itchy, scaly, red patches on the skin.
Rejection — Rejection occurs when the body recognizes a new transplanted organ as "foreign" and turns on the immune system of the body.
T cells — Any of several lymphocytes that have specific antigen receptors, and that are involved in cell-mediated immunity and destruction of antigen-bearing cells.
Transplantation — The removal of tissue from one part of the body for implantation to another part of the body; or the removal of tissue or an organ from one individual and its implantation in another individual by surgery.
Immunosuppressant drugs may interact with other medicines. When this happens, the effects of one or both drugs may change or the risk of side effects may be greater. Other drugs may also have an adverse effect on immunosuppressant therapy. This is particularly important for patients taking cyclosporin or tacrolimus. For example, some drugs can cause the blood levels to rise, while others can cause the blood levels to fall and it is important to avoid such contraindicated combinations. Other examples are:
- The effects of azathioprine may be greater in people who take allopurinol, a medicine used to treat gout.
- A number of drugs, including female hormones (estrogens), male hormones (androgens), the antifungal drug ketoconazole (Nizoral), the ulcer drug cimetidine (Tagamet) and the erythromycins (used to treat infections), may increase the effects of cyclosporine.
- When sirolimus is taken at the same time as cyclosporin, the blood levels of sirolimus may be increased to a level where there are severe side effects. Although these two drugs are usually used together, the sirolimus should be taken four hours after the dose of cyclosporin.
- Tacrolimus is eliminated through the kidneys. When the drug is used with other drugs that may harm the kidneys, such as cyclosporin, the antibiotics gentamicin and amikacin, or the antifungal drug amphotericin B, blood levels of tacrolimus may be increased. Careful kidney monitoring is essential when tacrolimus is given with any drug that might cause kidney damage.
- The risk of cancer or infection may be greater when immunosuppressant drugs are combined with certain other drugs which also lower the body's ability to fight disease and infection. These drugs include corticosteroids such as prednisone; the anticancer drugs chlorambucil (Leukeran), cyclophosphamide (Cytoxan) and mercaptopurine (Purinethol); and the monoclonal antibody muromonab-CD3 (Orthoclone), which also is used to prevent transplanted organ rejection.
Not every drug that may interact with immunosuppressant drugs is listed here. Anyone who takes immunosuppressant drugs should let the physician know all other medicines he or she is taking and should ask whether the possible interactions can interfere with treatment.
Abbas, A. K., and A. H. Lichtman. Basic Immunology: Functions and Disorders of the Immune System. Philadelphia: W. B. Saunders Co., 2001.
Sompayrac, L. M. How the Immune System Works. Boston: Blackwell Science, 1999.
Travers, P. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Publishers, 2001.