Mycophenolate is an active substance which weakens the effect of the immune system. It is therefore mainly used to suppress rejection reactions in organ transplantation. However, many side effects must be expected with its use.
What is mycophenolate?
Mycophenolate is mainly used to suppress rejection reactions in organ transplants. Mycophenolate is an immunosuppressant that is often used with other drugs such as ciclosporin or corticosteroids in organ transplantation. It is a complex chemical compound that interferes with nucleic acid metabolism. The drug was developed as mycophenolate mofetil by the American pharmaceutical company Synthex. It was launched in the USA under the name CellCept in 1995. It was one of the first drugs to be approved in Europe through a centralized approval process for 15 countries. As a chemical compound, it exists as an almost white crystalline powder. It is insoluble in water. However, it dissolves somewhat in absolute alcohol. The melting point of the active ingredient is 93 to 94 degrees Celsius. Mycophenolate mofetil is a so-called prodrug. It is converted in the organism into the active substance mycophenolic acid. This active ingredient is also commercially available as a sodium salt under the trade name Myfortic. In this form, the drug is a water-soluble active substance. The sodium salt is also converted in the body into the active form mycophenolic acid.
Pharmacologic action
Mycophenolic acid (MPA) is a drug that inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH). Inosine monophosphate dehydrogenase is responsible for the synthesis of guanosine. Guanosine is in turn a basic building block of the nucleic acids DNA and RNA. It contains the important purine base guanine. By inhibiting IMPDH, guanosine is also no longer synthesized. All processes dependent on nucleic acid formation are also suppressed. However, the inhibition of the enzyme is selective and reversible. Thus, no other enzymes are inhibited, and after discontinuation of the drug, the synthesis of guanosine immediately resumes. However, the selectivity also means that, unlike other immunosuppressants, the formation of B- and T-lymphocytes is increasingly and selectively inhibited. Immune cells, more than any other cells, depend on the new synthesis of purine nucleotides because they proliferate rapidly and their needs cannot be adequately met by the decay of old cells. However, this new synthesis of purine bases, especially guanosine, fails completely here. Other body cells, which do not proliferate so strongly, still have the possibility to use recycled purine bases from the decomposition of old nucleic acids. However, the immune system is highly dependent on the availability of a sufficient amount of nucleic acids, since it has to produce a large number of immune cells. For example, new T lymphocytes, B lymphocytes, natural killer cells or macrophages must be constantly available to ensure sufficient immune protection for the organism. However, these cells are also produced for the execution of the rejection reactions after organ transplantations. For this case the immune system should be suppressed. However, the effectiveness of mycophenolate is so strong that it should really only be used after organ transplants. This is because the side effects are so severe that its use in autoimmune diseases, for example, would tend to have adverse consequences.
Medical application and use
The main application of mycophenolate, as mentioned above, is its use in organ transplantation. It is mainly used in kidney, liver, or heart transplants. However, mycophenolate is always used together with ciclosporin and the corticosteroids to suppress the immune system. Medication starts two days after transplantation by oral tablets. The effect is selective. Unlike some other immunosuppressants, the metabolite mycophenolic acid is not incorporated into DNA. Only the new synthesis of purine bases is suppressed. As a result, a normal immune response immediately resumes after discontinuation of the drug. The effect of mycophenolate is very strong. However, this allows the drug to suppress the rejection reactions very well.
Risks and side effects
This strong immunosuppressive effect of mycophenolate causes violent side effects on the other side. The side effects are often severe and occur in large numbers. Common side effects include anemia, thrombocytopenia, nausea, vomiting, and diarrhea. Anemia is caused by inhibition of hematopoiesis due to lack of nucleic acid synthesis. In addition, immunosuppressive treatment is accompanied by frequent infections such as herpes simplex, herpes zoster, candidiasis, and even sepsis. There have even been reports of malformations in newborn children whose mothers were treated with mycophenolate in combination with other immunosuppressants. In a few cases, the development of life-threatening progressive multifocal leukoencephalopathy (PML) also occurs. PML is an infection of the central nervous system with polyomaviruses that only severely immunocompromised individuals can acquire. The disease progresses rapidly and causes numerous neurological deficits that can eventually be fatal. Furthermore, as with the other immunosuppressants, there is a possibility of developing skin cancer. Therefore, it is important to avoid exposure to UV radiation from the sun during treatment.
