What is mycophenolate mofetil (MMF), an immunosuppressive medication?

From the Guidelines

Mycophenolate mofetil is an immunosuppressant medication that acts by inducing apoptosis in lymphocytes through inhibition of the de novo synthesis of purines, and is primarily used to prevent organ rejection in solid organ transplants and as a standard component of GVHD prophylaxis regimens.

Key Points

• Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid, which inhibits the de novo synthesis of purines, leading to apoptosis in lymphocytes 1.
• The typical adult dosage of MMF ranges from 1 to 3 grams daily, usually divided into two doses, and common brand names include CellCept and Myfortic (mycophenolate sodium, a related compound).
• MMF is often prescribed for conditions such as lupus nephritis, rheumatoid arthritis, vasculitis, and inflammatory myopathies, as well as for the prevention of organ rejection in transplant recipients and the treatment of certain autoimmune disorders.
• Patients taking MMF should be aware of potential side effects, including gastrointestinal disturbances, increased risk of infections, and potential birth defects if taken during pregnancy, and regular blood monitoring is necessary to check for bone marrow suppression 1.

Clinical Use

• MMF has been shown to be effective in treating steroid-refractory acute graft-versus-host disease (aGVHD), with an overall response rate (ORR) of 47% and a complete response (CR) rate of 31% in one prospective phase II trial 1.
• The use of MMF in the treatment of bullous pemphigoid has also been reported, with doses of 0.5-1 g twice daily showing effectiveness in controlling the disease, although further evidence is needed to determine its role in this condition 1.

Important Considerations

• The choice of MMF as a treatment option should be based on the individual patient's condition, medical history, and potential risks and benefits, and should be made in consultation with a qualified healthcare professional.
• Regular monitoring of the patient's condition and adjustment of the treatment plan as needed is crucial to ensure the safe and effective use of MMF.

From the FDA Drug Label

Mycophenolate mofetil is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

Mycophenolate mofetil is an immunosuppressive agent used to prevent rejection in people who have received a kidney, heart, or liver transplant. It works by inhibiting the de novo pathway of guanosine nucleotide synthesis, which is necessary for the proliferation of T- and B-lymphocytes. Mycophenolate mofetil is available for oral administration as capsules and tablets. 2 2 2

Key points:

• Mycophenolate mofetil is an immunosuppressive agent.
• It is used to prevent rejection in transplant patients.
• It works by inhibiting the de novo pathway of guanosine nucleotide synthesis.
• It is available as capsules and tablets.

From the Research

Definition and Mechanism of Action

• Mycophenolate mofetil is an immunosuppressive drug that inhibits the proliferation of T and B lymphocytes 3, 4, 5.
• It is a prodrug that is rapidly hydrolyzed to mycophenolic acid after oral administration, which then inhibits de novo purine synthesis 3.
• Mycophenolic acid is a competitive, selective, and reversible inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), an important rate-limiting enzyme in purine synthesis 6.

Clinical Uses

• Mycophenolate mofetil is used to prevent or treat allograft rejection after solid-organ transplantation, including kidney, liver, and heart transplants 3, 4, 5, 7.
• It is also used to treat refractory rejection in renal, heart, and liver transplant recipients, and may have efficacy in the treatment of chronic rejection 5.
• Mycophenolate mofetil has been shown to improve graft and patient survival in liver transplant patients, and can be used to spare calcineurin inhibitors and reduce their adverse effects 4, 7.

Pharmacokinetics and Toxicology

• Mycophenolate mofetil has a high absolute bioavailability of 94% for oral administration, and the maximum plasma concentration of mycophenolic acid occurs after two hours 3.
• Mycophenolic acid undergoes hepatic glucuronidation to an inactive salt that is renally excreted 3.
• The drug exhibits large between- and within-subject pharmacokinetic variability, and may display nonlinear pharmacokinetics with decreasing bioavailability at higher doses 6.
• The most common adverse effects of mycophenolate mofetil are gastrointestinal complaints, such as diarrhea, which can often be managed with dose reduction or withdrawal of the drug 3, 4, 7.