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Mycophenolic acid (INN) (pronounced /ˌmaɪkoʊˈfɛnɒlɪk/) or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It was initially marketed as the prodrug mycophenolate mofetil (abbreviated MMF) to improve oral bioavailability. More recently, the salt mycophenolate sodium has also been introduced. Mycophenolic acid is commonly marketed under the trade names CellCept (mycophenolate mofetil; Roche) and Myfortic (mycophenolate sodium; Novartis).
Mycophenolate is derived from the fungus Penicillium stoloniferum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It inhibits inosine monophosphate dehydrogenase, the enzyme which controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes.
Mycophenolate is potent and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of a three compound regimen of immunosuppressants, also including a calcineurin inhibitor (cyclosporin or tacrolimus) and prednisolone.
Generally speaking, mycophenolate is used for the prevention of organ transplant rejection. Specifically, mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and renal transplant rejection in children >2 years; while mycophenolate sodium is indicated for the prevention of renal transplant rejection in adults. Mycophenolate sodium has also been used for the prevention of rejection in liver, heart and/or lung transplants in children >2 years.
An immunosuppressant which has drastically decreased the incidence of acute rejection in solid transplant recipients, mycophenolate is increasingly utilized as a steroid sparing treatment in immune-mediated disorders including immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis.
Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications  compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy. Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side effects. Walsh et al. even propose that mycophenolate should be considered as a first line induction therapy for treatment of lupus nephritis in patients without renal dysfunction, suggesting that mycophenolate will be encountered more frequently in medical practice.
Common adverse drug reactions (≥1% of patients) associated with mycophenolate therapy include: diarrhea, nausea, vomiting, infections, leukopenia, and/or anemia. Mycophenolate sodium is also commonly associated with fatigue, headache and/or cough. Intravenous (IV) administration of mycophenolate mofetil is also commonly associated with thrombophlebitis and thrombosis. Infrequent adverse effects (0.1–1% of patients) include: esophagitis, gastritis, gastrointestinal tract hemorrhage, and/or invasive cytomegalovirus (CMV) infection.
Comparison to other agents
Compared with azathioprine it is more lymphocyte-specific and is associated with less bone marrow suppression, fewer opportunistic infections and lower incidence of acute rejection. The exact role of mycophenolate vs azathioprine has yet to be conclusively established, but many centers use it in place of azathioprine for high-risk patients, or patients who have already experienced an episode of acute rejection. In long-term immunosuppression, it may be used to avoid calcineurin inhibitors or steroids.
Potential future uses
It is also currently being used as a long term therapy for maintaining remission of Wegener's Granulomatosis. A combination of mycophenolate and ribavirin has been found to stop infection by and replication of dengue virus in vitro.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Mycophenolic_acid". A list of authors is available in Wikipedia.|