Mycophenolate Mofetil And Its Use in Autoimmune Skin Conditions

What Is Mycophenolate?

Mycophenolate is also known as mycophenolate mofetil. It is a powerful medication used to suppress immune function. In the 1980s, mycophenolate was originally isolated as a fermentation product from a bacterium called Penicillium stoloniferum.^[1,2] It is now used to treat a number of moderate to severe immune-mediated (autoimmune and autoinflammatory) skin conditions and has been used in transplant patients to prevent solid-organ rejection.^[3]

Brand names that are associated with this medication include the following:

Cellcept

Myfortic

How Does Mycophenolate Work?

Mycophenolate works by inhibiting an enzyme called inosine monophosphate dehydrogenase (IMPDH), an important enzyme used to make and recycle DNA in our cells.^[4] Mycophenolate can suppress immune function by selectively binding to a form of inosine monophosphate dehydrogenase that is expressed in a type of activated immune cell called a lymphocyte.^[1,4] By selectively targeting these immune cells, mycophenolate can treat immune-mediated conditions without having too much effect on other cells types or organs in our body.

What Conditions Does Mycophenolate Treat? 

Mycophenolate is FDA-approved for prevention of solid-organ (kidney, heart, and liver) transplant rejection.­­­­^[1,3]

Mycophenolate is often used off-label by physicians for a large number of other skin conditions, including immunobullous diseases such as pemphigus and bullous pemphigoid; autoimmune connective tissue diseases; auto-inflammatory diseases such as psoriasis, vasculitis (inflammation of the blood vessels), and eczema.^[1]

How Is Mycophenolate Given?

Mycophenolate can be taken orally via capsules, tablets, and liquid suspension. There is also a solution formulation that can be administered intravenously.^[3]

Mycophenolate intravenous formulation can be administered as soon as 24 hours after an organ transplant and is typically switched to oral formulation as soon as the patient can tolerate oral medications. Mycophenolate is taken together with other immunosuppressive medications such as cyclosporine, tacrolimus and/or prednisone after an organ transplant.^[3]

What Are the Potential Side Effects and Risks of Mycophenolate?

• Gastrointestinal symptoms such as abdominal pain, nausea, diarrhea, and vomiting are the most common side effects of mycophenolate and are more severe with higher doses. This can be decreased by taking the medication with food or breaking into 2-3 doses per day. Myfortic, also known as enteric-coated mycophenolate sodium (EC-MPS), is a formulation that delays mycophenolate’s release into the gastrointestinal tract. This allows the medication to be broken down in the small intestine and not the stomach, which helps to lower gastrointestinal upset.^[5] 

• Mycophenolate may cause intestinal bleeding in up to 3% of kidney transplant patients, 1.7% heart transplant patients, and 5.4% liver transplant patient.^[3] Therefore patients with pre-existing stomach or intestinal ulcer diseases, who have bleeding disorders, or who are taking medications to prevent clotting are at higher risk for intestinal bleeding.

• Because mycophenolate suppresses immune function, people who take this medication are at a higher risk for getting or reactivating dormant infections. Some of these include herpes simplex virus (HSV), herpes zoster virus (VZV or shingles), and cytomegalovirus.^[3,6] The risks of infection are higher when combined with other immunosuppressive medications, as in the case of most transplant patients. Those considering mycophenolate should discuss getting the shingles vaccine with their physician before starting the medication. When on mycophenolate, a person’s body may not effectively mount an immune response to the shingles vaccine and may be at risk for infection, since it is a live vaccine. Therefore, all vaccines should ideally be given prior to starting immunosuppressive medications like mycophenolate.^[7]

• Mycophenolate oral suspension contains aspartame, an amino acid used to make another amino acid called phenylalanine in our body.^[3] People who have phenylketonuria, a condition where the body is unable to metabolize phenylalanine, should avoid taking mycophenolate.

• Mycophenolate falls within category D for pregnancy because it is associated with increased pregnancy loss during the first trimester and increased birth defects. Therefore, women of childbearing potential who take mycophenolate need to use two forms of highly effective contraception beginning at least one month before starting mycophenolate. Contraception should be continued for at least six weeks after stopping mycophenolate.^[3] There have been no human studies looking at the risk of breastfeeding while taking mycophenolate. However, studies in rats have shown that mycophenolate can be excreted in breast milk and therefore may have serious implications for nursing infants. Learn more about the use of mycophenolate during pregnancy

• Mycophenolate may lower the level of all 3 types of blood cells, including white blood cells (increased risk for infection), red blood cells (cause anemia), and platelets (increase bleeding risk).^[1,3]

• People who take mycophenolate along with other immunosuppressive medications have a higher risk of developing lymphoma and other cancers. Cancer risk is higher in people who are taking the medication(s) for longer durations and at higher doses.^[1,3] Lymphoma and blood-related malignancies can develop in 0.4-1% of the population taking mycophenolate with other immunosuppressive medications for solid-organ transplant.^[3] Interestingly, heart transplant patients taking mycophenolate (who typically require higher doses of immunosuppressive medications) compared to patients taking other immunosuppressive medications (such as azathioprine which increases the risk of nonmelanoma skin cancers)are 30% less likely to get squamous cell carcinoma skin cancers. It appears that the risk of developing basal cell carcinoma skin cancers is not affected by immunosuppressive medications.^[8]

• Other potential adverse reactions from mycophenolate include skin rash, dizziness, insomnia, back pain, weakness, tremors, and difficulty breathing.^[3]