Mycophenolic acid
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Systematic (IUPAC) name | |
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(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid | |
Clinical data | |
[[Regulation of therapeutic goods |Template:Engvar data]] |
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Pregnancy category | |
Routes of administration | Oral, IV |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | 94% (mofetil), 72% (sodium) |
Protein binding | 97% |
Metabolism | Hepatic |
Biological half-life | 16–18 hours |
Excretion | Renal 93% |
Identifiers | |
CAS Number | 24280-93-1 |
ATC code | L04AA06 (WHO) |
PubChem | CID 446541 |
Chemical data | |
Formula | C17H20O6 |
Molar mass | 320.34 g·mol−1[[Script error: No such module "String".]] |
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Mycophenolic acid (INN) (pronounced /ˌmaɪkoʊfɨˈnɒlɪk/) or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It was initially marketed as the prodrug mycophenolate mofetil (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).
Contents
Clinical use
Indications
In general, mycophenolate is used for the prevention of organ transplant rejection. Mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and renal transplant rejection in children over 2 years; whereas 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.[1]
An immunosuppressant that 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.[2]
Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications [2] compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy.[3] Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side-effects.[3] 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,[4] suggesting that mycophenolate will be encountered more frequently in medical practice.
Comparison to other agents
Compared with azathioprine it has significantly higher incidence of diarrhoea, and no difference in risk of any of the other side effects.[5] Mycophenolic acid is 15 times more expensive than azathioprine[6] The exact role of mycophenolate vs azathioprine has yet to be conclusively established. In long-term immunosuppression, it may be used to avoid calcineurin inhibitors or steroids.
Potential future uses
Mycophenolate mofetil is beginning to be used in the management of auto-immune disorders such as idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), scleroderma (Systemic sclerosis or SSc) and pemphigus vulgaris (PV) with success for some patients.[7]
It is also currently being used as a long-term therapy for maintaining remission of C-ANCA positive (Wegener's) granulomatosis. A combination of mycophenolate and ribavirin has been found to stop infection by and replication of dengue virus in vitro.[8][9]
Adverse effects
Common adverse drug reactions (≥1% of patients) associated with mycophenolate therapy include diarrhoea, 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.[1] Several cases of pure red cell aplasia (PRCA) have also been reported.[10]
The U.S. Food and Drug Administration (FDA) has issued an alert that patients on mycophenolate mofetil and mycophenolic acid are at increased risk of opportunistic infections, such as activation of latent viral infections, including BK-virus associated nephropathy. In addition the FDA is investigating 16 patients that developed a rare neurological disease while taking the drug. The neurological condition known as progressive multifocal leukoencephalopathy attacks the brain and central nervous system and is usually fatal.[11]
Mycophenolic acid is associated with miscarriage and congenital malformations when used during pregnancy, and should be avoided whenever possible by women trying to conceive.[12][13]
Pharmacology
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 that 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.[14]
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.
References
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External links
- MedlinePlus drug information: mycophenolate (systemic) – information from USP DI Advice for the Patient
es:Ácido micofenólico hu:Mikofenolát-mofetil nl:Mycofenolzuur ja:ミコフェノール酸モフェチル pl:Kwas mykofenolowy ru:Микофенолата мофетил
vi:Mycophenolic- ↑ 1.0 1.1 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3[page needed]
- ↑ 2.0 2.1 Moore RA, Derry S (2006). "Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis". Arthritis Research & Therapy. 8 (6): R182. doi:10.1186/ar2093. PMC 1794528 Freely accessible. PMID 17163990.
- ↑ 3.0 3.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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- ↑ Remuzzi G, Lesti M, Gotti E; et al. (2004). "Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial". Lancet. 364 (9433): 503–12. doi:10.1016/S0140-6736(04)16808-6. PMID 15302193.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Diamond MS, Zachariah M, Harris E (2002). "Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA". Virology. 304 (2): 211–21. doi:10.1006/viro.2002.1685. PMID 12504563.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ "CellCept (mycophenolate mofetil) August 2009". U.S. Food and Drug Administration. August 14, 2009. Retrieved 2009-08-21.
- ↑ [1][dead link]
- ↑ [2][dead link]
- ↑ "MedWatch Safety Alerts for Human Medical Products". Fda.gov. 2010-03-22. Retrieved 2010-07-28.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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