Immunosuppressants
The immunosuppressants are a class of drugs capable of inhibiting the body's immune system. Many of the agents included in this category are also cytotoxic (cell poisons) and are used in the treatment of cancer. Cytotoxic agents used as immunosuppressants include antimetabolites (azathioprine), alkylating agents (cyclophosphamide), and folic-acid antagonists (methotrexate or 6-MP). Other immunosuppressants include mycophenolate (CellCept) and cyclosporin. These drugs are used in organ transplant patients to decrease the body's own natural defense to foreign bodies (such as the transplanted organ) and thereby, attempt to prevent the organ's rejection by the body. This same reduction in the body's own defenses make it useful in the the treatment of autoimmune diseases.
Azathioprine (Imuran) is more effective in suppressing proliferating (dividing) lymphocytes; it is less active against non-dividing cells. Azathioprine is a relatively toxic drug. After azathioprine gets into the blood stream, it is changed by the liver to a chemical called "6-mercaptopurine" (6-MP). It generally takes 6-12 weeks to start working. A common starting dose for adults is 50mg per day. After 4 to 8 weeks, the dose may be increased. Most adults require 50-150mg per day. IMPORTANT: Imuran can cause irreversible bone marrow failure for those with a particular polymorphism of the TPMT gene. GlaxoSmithKline has a predictive DNA test for this type of problem.
Mycophenolate (MFM or CellCept) has only been on the market for the last 5 years. MFM inhibits lymphocyte proliferation and antibody formation, it interferes with the production of certain white blood cells. This drug may have some advantages over azathioprine, in that it may have a lower risk of malignancies such as leukemia or lymphoma. This advantage is not proven, however, and it may be a very long time before this possible advantage can be substantiated. The capsules come in 250mg and 500mg and the usual dose for adults is 1-1.5 g (2-6 capsules) twice a day. The dose for children is 15mg/kg/day. The cost for a pharmacist is $450.00 for a month's supply for an adult, compared to $100.00 for Imuran.
Cyclosporine (Sandimmune) has a powerful immunosuppressive activity affecting especially the T lymphocytes. It is toxic to the human kidney, and there is fear that prolonged use of the agent could lead to permanent renal damage. It also increases the growth of hair on the face and body, which can be distressing to female patients. It is a difficult drug to use because since it is fat soluble and its absorption is variable. Thus each patient needs to be individually studied to ensure that the dosage is adequate but not excessive. Grapefruit juice and Mediterranean oranges and Sun Drop, a citrus soda, contain bergamottin which enhances the effect of cyclosporine, increasing the level of the drug in circulation. St. John's wort reduces the concentration of cyclosporine rendering it less effective.
Mercaptopurine (6-MP) belongs to a group of drugs known as antimetabolites. It is used to treat many types of autoimmune diseases. It may interfere with the normal menstrual cycle in women and may stop sperm production in men. The usual adult dose is 2.5mg/kg/day (100-200mg). The pediatric dose is 50mg per day. A maintenance dosage after remission is 1.5-2.5mg/kg/day.
Precautions
Avoid exposure to infections. Stay away from crowds and people known to have colds, the flu, or other infections.
Do not take these drugs with other drugs, including over-the-counter medications, without first checking with your doctor.
To minimize potential problems, wash your hands before touching eyes or the inside of your nose after handling these drugs.
These drugs can cause fetal harm when administered to a pregnant woman. They should not be given during pregnancy without careful weighing of the risk versus benefit. Whenever possible, use of immunosuppressive drugs in pregnant patients should be avoided. They should not be used in nursing mothers.
Regular blood tests should be performed, as these drugs can lower your other blood counts.
Side Effects
These include stomach upset, nausea, vomiting, abdominal pain, mouth ulcers, darkened urine, pale stools, jaundice (yellowing of the skin or white portion of the eyes), unusual bleeding or bruising. A serious (and life threatening) side effect is reduced activity of bone marrow, but this can be monitored with regular blood tests. Occasionally, patients taking immunosuppressants will develop pancreatitis (inflammation of the pancreas) some months after starting these drugs.