Mycophenolate Mofetil (MMF; brand name: Cellcept, Genentech, Inc) is an antimetabolite immunosuppressant that originally is used with hearts, kidneys and livers transplantation to prevent rejection. It is a pro-drug of mycophenolate acid with a higher oral bioavailability than active metabolite Mycophenolic acid (MPA) or Mycophenolate sodium (Myfortic; Novartis, inc) which is an enteric-coated formulation of mycophenolate acid.
Recently, European Thyroid Association (ETA)/European Group on GO (EUGOGO) guidelines for the management of Graves’ orbitopathy (GO), also called thyroid eye disease (TED) or thyroid-associated orbitopathy (TAO), concluded that based on available evidences Mycophenolate has a good efficacy and safety profile in patients with moderate-to-severe and active GO, both as monotherapy and in combination with i.v. glucocorticoids. EUGOGO recommended a combination of moderate cumulative dose of i.v. methylprednisolone and daily dose of oral enteric-coated mycophenolate sodium as the first-line treatment for patients with moderate-to-severe and active GO (with or without diplopia). 
This also can be used as a glucocorticoid-sparing agent in a number of other rheumatologic conditions such as systemic lupus erythematosus, lupus nephritis, systemic sclerosis, inflammatory myopathies, behcet’s disease, pemphigus vulgaris, psoriasis, and IgA nephropathy among many others.
CellCept should not be given to patients with hypersensitivity to mycophenolate mofetil and should not be used in pregnancy nor in women of childbearing potential or women who are breast-feeding. 
MPA, the active metabolite of MMF was first isolated in 1896 by Italian microbiologist and physician Bartolomea Gaseo from the fungus Penicillium brevicompactum. The first antibiotic described, MPA fell into obscurity due to adverse effects before it was rediscovered in 1912 by Alsburg and Black who noted its antimicrobial properties and later in the 1960’s by William Sweeney et al as an experimental cancer treatment - exhibited growth inhibition of rodent solid tumors. Eventually Cellcept (MPA prodrug MMF) was developed by Allson and Eugui as an immunomodulator for autoimmune diseases involving the IMP dehydrogenase pathway and immune rejection in organ transplantation and was FDA approved for use in kidney transplantation in 1995.
Absorption For adults: 0.63- 1.8 hours For Pediatrics: 0.604 to 3.03 hours Bioavailability (Oral): 94% Food decreases Cmax by 40% no effect on AUC
Distribution Protein binding (Albumin): 97% Volume of Distribution: 4L/kg
Metabolism Rapidly and extensively metabolized in the liver by esterases Active component: Mycophenolic acid Inactive component: Mycophenolic acid glucuronide
Excretion Renal: 93%; ~88% of which is metabolites Fecal: 6% Bile: unknown amount Total body clearance: 193 mL/min (mycophenolic acid)
Elimination Half Life: 17.9 hours (PO) and 16.6 hours (IV) for the active metabolite
Mechanism of Action
Mycophenolate mofetil is a prodrug that is quickly metabolized to mycophenolic acid. It reversibly inhibits inosine monophosphate (IMP) dehydrogenase, which is necessary for the conversion of IMP to guanosine monophosphate (GMP) in DNA replication. This conversion step is the rate limiting step in the de novo synthesis of purine nucleotides; without this step, there is decreased B- and T-cell proliferation, as well as antibody production. MPA also binds IMP expressed on activated T lymphocytes, induces apoptosis of activated T lymphocytes and inhibits lymphocyte recruitment and adhesion molecule expression, by preventing the glycosylation of lymphocyte and monocyte glycoproteins.
Indications and Uses
FDA-Labeled Indications (per IBM Micromedex Drug Reference) Cardiac, liver, and renal transplant rejection prophylaxis- in combination with cyclosporine and corticosteroids
Non-FDA Labeled Indications (per IBM Micromedex Drug Reference) Atopic dermatitis Autoimmune hepatitis Bullous pemphigoid Complication of transplanted pancreas Graft versus host disease Idiopathic thrombocytopenic purpura Kidney disease Lung disease with systemic sclerosis Lupus nephritis Myasthenia gravis, Generalized, acetylcholine receptor antibody positive Nephrotic syndrome; Adjunct Renal transplant rejection Renal transplant rejection, Alternative regimens Systemic sclerosis, diffuse Takayasu's disease
Dosing and Administration
MMF formulations, both generic and Cellcept, are supplied in oral capsule (250 MG), oral tablet (200 MG/1 ML), and oral powder for suspension (500 MG). Starting with lower doses at first (eg, 500 mg daily for several days) and titrating up to the target dose over several weeks may improve a patient's GI tolerance of MMF.
For chronic uveitis, a dose of 1-1.5g BID, in addition to <10 MG prednisone daily, is used.
The National Institute for Occupational Safety and Health (NIOSH) recommends the use of single gloves by staff handling tablets or capsules and the use of double gloves by staff handling the liquid formulation.
Safety and Adverse Effects
There is following consideration while taking CellCept: 
- Embryofetal Toxicity with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system.
- Lymphoma; Post-transplant lymphoproliferative disorder (PTLD) related to Epstein Barr Virus (EBV) infection; and other malignancies particularly of the skin
- Serious Infections including Polyomavirus-associated nephropathy (PVAN), JC virus-associated progressive multifocal leukoencephalopathy (PML), Cytomegalovirus (CMV) infections, viral reactivation in patients infected with Hepatitis B and C, COVID-19
- Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA)
- Gastrointestinal Complications including gastrointestinal bleeding requiring hospitalization, ulceration and perforations
- Gout disease: Patients with Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms.
- Acute Inflammatory Syndrome Associated with Mycophenolate Product
- During treatment with CELLCEPT, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines)
- Local Reactions with Rapid Intravenous Administration
- Risks in Patients with Phenylketonuria as CELLCEPT Oral Suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension).
- Donation of blood (for at least 6 weeks) and semen (for 90 days ) should not be done.
- CELLCEPT may impact the ability to drive and use machines.
Pregnancy Care should be taken in patients who are pregnant, expect to become pregnant, are breast feeding (excreted in breast milk) or who are of childbearing age. MPA increases the incidence of spontaneous abortion in the 1st trimester of pregnancy as well as the risk for congenital malformations such as Midline defects - cleft lip/palate and esophageal malformation Limb defects Organ defects - heart and kidney malformation Mycophenolate may also decrease the effect of contraception and additional or alternative forms of contraception should be used.
Drug Interactions Antacids, mineral supplements, bile acid sequestrants and proton pump inhibitors may decrease systemic absorption and subsequent serum concentrations of MPA Rifampin may decrease serum concentration of MPA due to effect on cytochrome 3A4/5 and 2C8. Acyclovir, Valacyclovir and Probenecid may increase serum concentration of MPA due to effects on cytochrome 3A4/5 and 2C8. Care should be taken when using additional immunosuppression such as Azathioprine as may increase toxicity.
Immunizations and Infection: The use of MPA is contraindicated in patients with active systemic infection as may cause worsening of infection and potentially death. Certain Immunizations are contraindicated when taking MPA such as:
- Live attenuated Influenza vaccine
- Live Measles, Mumps, and Rubella vaccine
- Live Varicella and Zoster vaccines
- Live Rotavirus vaccine
Patients who may start treatment with MPA should undergo testing such as:
- Complete blood count with differential (CBC)
- Liver function tests and albumin
- Creatine and urinalysis
- Hepatitis B and C virus
- Purified protein derivative of interferon gamma release assay for Tuberculosis
Side Effects Although less than 20% of patients report adverse effects, the most commonly reported side effects include dose dependent gastrointestinal distress and bone marrow suppression. Periodic monitoring of laboratory levels such as CBC may prevent life threatening cytopenias. Additional adverse effects include viral infections: Varicella Zoster (VZV) and Cytomegalovirus (CMV) as well as lymphoid neoplasms and Progressive Multifocal Leukoencephalopathy. Given its tolerable side effect profile, MPA is an effective steroid sparing agent, up to 85% of adults and 88% of children treated for chronic uveitis.
Additional Resources and Patient Assistance
1. Seo, P. (2017). Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases. UpToDate. Retrieved January 20, 2019 from https://www.uptodate.com/contents/mycophenolate-overview-of-use-and-adverse-effects-in-the-treatment-of-rheumatic-diseases?search=mycophenolate&source=search_result&selectedTitle=2~148&usage_type=default&display_rank=5
2. Silverman Kitchin, Jennifer E.; Pomeranz, Miriam Keltz; Pak, Grace; Washenik, Ken; Shupack, Jerome L. (1997). "Rediscovering mycophenolic acid: A review of its mechanism, side effects, and potential uses". Journal of the American Academy of Dermatology. 37 (3): 445–449. doi:10.1016/S0190-9622(97)70147-6.
4. CellCept (mycophenolate mofetil) August 2009". U.S. Food and Drug Administration. August 14, 2009. Retrieved 2009-08-21.
5. Fulton B, Markham A. "Mycophenolate mofetil: a review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation." Drugs. 1996, 51(2):278-98
6. Allison, AC; Eugui, EM (1993). "The design and development of an immunosuppressive drug, mycophenolate mofetil". Springer Seminars in Immunopathology. 14 (4): 353–80. doi:10.1007/bf00192309. PMID 8322167
7. Allison, AC; Eugui, EM (1996). "Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF)". Clinical Transplantation. 10 (1 Pt 2): 77–84. PMID 8680053
8. Allison, AC; Kowalski, WJ; Muller, CD; Eugui, EM (1993). "Mechanisms of action of mycophenolic acid". Annals of the New York Academy of Sciences. 696 (1): 63–87.
9. Ransom JT (December 1995). "Mechanism of action of mycophenolate mofetil". Therapeutic Drug Monitoring. 17 (6): 681–4. doi:10.1097/00007691-199512000-00023. PMID 8588241.
10. Sollinger HW. From mice to man: the preclinical history of mycophenolate mofetil. Clin Transplant. 1996;10(1 Pt 2):85–92.
11. BCSC American Academy of Ophthalmology: Intraocular Inflammation and Uveitis Volume 9; 2017-2018.
12. Mycophenolate Mofetil. (February 03, 2019). In Micromedex Drug Reference for Android (Version v1859) [Mobile application software]
- ↑ Bartalena, L., Kahaly, G. J., Baldeschi, L., Dayan, C. M., Eckstein, A., Marcocci, C., Marinò, M., Vaidya, B., Wiersinga, W. M., and EUGOGO (2021). The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. European Journal of Endocrinology 185, 4, G43-G67, available from: < https://doi.org/10.1530/EJE-21-0479> [Accessed 31 August 2022]
- ↑ https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
- ↑ https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40