Mycophenolate is an oral immunosuppressant used primarily to prevent organ rejection and to treat various autoimmune diseases.
Mycophenolate mofetil (CellCept) and mycophenolate sodium/mycophenolic acid (Myfortic).
A purine analog that reduces rejection rate in transplantation.
Most cells have two pathways for supplying purines to support DNA synthesis and cellular function: a de novo synthesis and salvage of nucleotides from DNA turnover.
Class: Disease-modifying anti-rheumatic drug (DMARD) and general immunosuppressive agent.
Prodrug (for MMF): converted to mycophenolic acid, a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), especially IMPDH II in lymphocytes.
Mycophenolate starves the cells of purines, particularly guanosine, by inhibiting inosine 5’phosphate dehydrogenase, enzyme that generates guanosine 5’ monophosphate from -5’ monophosphate.
The inadequate supply of guanosine inhibits both B and T cells.
An immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine.
Trade name Cellcept.
A reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) in purine biosynthesis, specifically guanine synthesis, which is necessary for the growth of T cells and B cells.
Blocks de novo guanine nucleotide synthesis, so T and B lymphocytes cannot proliferate effectively, reducing antibody production and cytotoxic responses.
Net effect: targeted impairment of lymphocyte replication with relatively less impact on other cell types that can use salvage pathways.It
Cells that are capable of recovering purines via a separate scavenger pathway are able to escape the effect.
Less toxic alternative to azathioprine.
Used in the treatment of autoimmune diseases, such as Behcet’s disease, pemphigus vulgaris, and systemic lupus erythematosus.
The addition of mycophenolate mofetil to a glucocorticoid for the first line treatment of ITP resulted in great response and the lower risk of refractory or relapsed ITP, with someone decrease quality of life.
The most common side-effects of this drug are high blood sugars and increased blood cholesterol levels, hypomagnesemia, hypocalcemia, hyperkalemia, and an increase in BUN are regularly noted.
pCommon: GI upset (nausea, diarrhea, abdominal pain), headache, fatigue.
Hematologic: leukopenia, anemia, thrombocytopenia; requires periodic CBC monitoring.
Coughing, shortness of breath and pleural effusions occur in one third of patients.
Back and abdominal pain, headache, nausea, diarrhea, and fever may occur.
Rarely associated with melanoma, lymphoma and other malignancies, with cancers of the skin being the most common site.
May be associated with abdominal pain, bradycardia, myalgias, and weakness.
Infectious risk: increased risk of serious bacterial, viral (including CMV, BK), and opportunistic infections due to immune suppression.
Oncologic risk: long-term use in transplant regimens is associated with higher risk of malignancies such as lymphomas and skin cancers.
Teratogenicity: strong association with first-trimester pregnancy loss and congenital malformations; strict contraception and REMS requirements apply.
Drug interactions: agents affecting enterohepatic recirculation or glucuronidation (certain antacids, bile acid sequestrants, some antivirals) can reduce exposure; other immunosuppressants can synergistically increase infection and malignancy risk.
Uses:
Solid-organ transplant: combined with calcineurin inhibitors and steroids to prevent kidney, heart, and liver allograft rejection.
Autoimmune diseases: systemic lupus (including lupus nephritis), rheumatoid arthritis, vasculitides, inflammatory bowel disease, systemic sclerosis, and various dermatologic and ocular autoimmune conditions.
When given in combination with glucocorticoids results in a better response with fewer treatment failures than glucocorticoids alone in ITP.
Dosing and administration
Oral, typically twice daily; available as tablets, capsules, and delayed-release formulations.
Dose and target exposure vary by indication, organ type, and concomitant immunosuppression; renal function and GI tolerability often drive adjustments.