Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases
- Philip Seo, MD
Philip Seo, MD
- Assistant Professor of Medicine
- Johns Hopkins University School of Medicine
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Clinical professor, University of Washington, Seattle
- Clinical professor, University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific Arthritis Associates
Mycophenolate (also known as mycophenolic acid [MPA]), a powerful inhibitor of lymphocyte proliferation, has been used since the early 1990s for the prevention of acute allograft rejection. Mycophenolate is also widely used as a glucocorticoid-sparing agent for the treatment of patients with a variety of rheumatic diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), inflammatory myopathies, and some systemic vasculitides.
General principles regarding the use of mycophenolate for the treatment of rheumatic diseases and the side effects associated with its use are discussed in this topic review. The use of mycophenolate in specific autoimmune disorders, organ transplantation, and other conditions with presumed immunologic bases (eg, Crohn disease) is presented separately. (See appropriate topic reviews.)
Pharmacokinetics — Mycophenolic acid (MPA) is available in two formulations: mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). MMF is a prodrug that was developed to improve the bioavailability of MPA. EC-MPS has the potential to reduce the incidence of adverse gastrointestinal (GI) effects, principally diarrhea, by delaying release of MPA into the small intestine instead of the stomach. Both formulations are rapidly hydrolyzed to the active metabolite MPA [1,2].
The bioavailability of both formulations is approximately 90 percent but is significantly reduced when taken with a high-fat meal. Accordingly, both formulations should be taken on an empty stomach to increase absorption. Alternatively, to improve GI tolerability, the MMF formulation may instead be taken with meals at consistent times each day.
A dose of 720 mg EC-MPS is therapeutically equivalent to 1000 mg of MMF [2-4]. However, the two formulations should not be interchanged indiscriminately because the rate and extent of absorption of these two products is not equivalent. In some patients, it is necessary to convert from MMF (CellCept) to EC-MPS (Myfortic) to improve GI tolerability. When this occurs, added monitoring of clinical effect is warranted.
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- Mechanism of action
- Active infection
- PRETREATMENT CONSIDERATIONS
- Drug interactions
- Immunization requirements
- Laboratory and clinical testing
- Prophylaxis for Pneumocystis jirovecii
- MYCOPHENOLATE DOSE AND ADMINISTRATION
- Drug dose
- ADVERSE EFFECTS
- Bone marrow suppression
- - Pneumocystis jirovecii
- - Viral infections
- - Progressive multifocal leukoencephalopathy