Continuing medical education
Mycophenolate mofetil in dermatology

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Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA), a medication used to treat psoriasis in the 1970s until side effects and the concern of carcinogenesis led to its discontinuation. The prodrug, MMF, emerged decades later in the transplant field. Dermatologists have since used MMF off-label to treat various inflammatory skin conditions, with most research concentrating on its use in psoriasis, autoimmune blistering disorders, dermatitides, and connective tissue disorders. The appeal of MMF is predicated upon its lymphocyte specificity and consequent decreased toxicity profile. These attributes may make it a preferable treatment option. Its use in the field of dermatology is currently limited by a lack of randomized controlled trials, potential unknown side effects, and cost of treatment. In reviewing both current literature and our own clinic records, MMF appears to be a promising therapeutic option for the treatment of cutaneous inflammatory diseases.

Learning objective

After completing this learning activity, participants should be able to summarize the history and pharmacology of mycophenolate mofetil as an immunosuppressant; recognize its potential role in the treatment of dermatologic conditions, including general dosing guidelines, use in pregnancy and pediatrics, and potential adverse effects; and identify future considerations and developing areas of research regarding the use of mycophenolate mofetil in dermatology.

Section snippets

History

Mycophenolate mofetil (MMF) is a prodrug of an older drug, mycophenolic acid (MPA). MPA was isolated as a fermentation product of Penicillium stoloniferum cultures by Gosio in 1896.1 In the 1940s, antifungal and antibacterial activity of MPA were recognized.2 It was studied as a potential antibiotic until the 1970s, when its antiviral, antitumor, and immunosuppressive properties were elucidated.3, 4 MPA was used as a systemic agent to treat psoriasis in the 1970s.5, 6 However, its tolerability

Pharmacokinetics

Following oral or parenteral administration of MMF, the 2-morpholino-ethyl ester of MPA (Fig 1), it is rapidly and completely hydrolyzed to its parent compound, MPA, by plasma esterases. In healthy adults, the oral bioavailability of the active drug, MPA, is 94% when compared to intravenous infusion. The volume of distribution is 3.6 and 4.0 L/kg following parenteral and oral administration, respectively. Ninety-seven percent of MPA circulates bound to plasma albumin. Hemodialysis has not been

Mycophenolate mofetil use in dermatology

Like many other immunosuppressive agents used in the transplant field, MMF has also demonstrated a therapeutic effect against inflammatory skin diseases. Such applications are currently available solely off-label because of a lack of large randomized clinical trials. However, evidence is growing that MMF may be useful in treating a variety of dermatologic conditions (Table I). The appeal of MMF in dermatology is largely related to both its steroid-sparing effects and its relative lack of

Common side effects

MMF is generally a well tolerated immunosuppressive agent with a preferred side effect profile compared to other immunosuppressives, because MMF has less nephrotoxic, hepatotoxic, and neurotoxic effects. The most commonly reported side effects are GI and are dose-dependent, occurring in up to 20% of patients at doses of 2 g daily. Patients mostly complain of diarrhea, nausea, vomiting, abdominal pain, anal tenderness, soft stools, frequent stools, and constipation that are usually mild and

Drug interactions

Drug interactions with MMF can be broken down into those that reduce levels of MMF, those that increase levels of MMF, and those in which mycophenolate reduces drug levels (Table III).

Reports have shown several medications that may result in decreased levels of MMF when administered concomitantly. Studies have shown a decrease in bioavailability of MMF with long-term coadministration with rifampin.142 Fluoroquinolones and metronidazole have also been shown to decrease the bioavailability of

Dosing and monitoring

MMF is marketed by Roche Pharmaceuticals (Nutley, NJ) and is available in 250 mg capsules, 500 mg tablets, 200 mg/mL oral suspension, and 500 mg vials for intravenous injection. The cost of a month's supply of MMF is approximately $850, which is likely one of the greatest limitations to its use.

The dosing recommendations of MMF published in the Roche Pharmaceuticals package insert are given in regard to its use in renal, cardiac, and hepatic transplant patients, because these are the only

Pregnancy

For reasons of safety, there have not been any well controlled studies of MMF in pregnant women. However, in animal studies, MMF has proven to be teratogenic, causing fetal resorptions and malformations.154 There have been several case reports illustrating fetal malformations resulting from women taking MMF for transplant suppression while pregnant. One study reported defects in four of 15 live born infants with exposure to MMF. These malformations included hypoplastic nails with shortened

Discussion and our experience

A retrospective chart review of our records at the University of Florida Dermatology Clinic yielded 34 patients who had been prescribed MMF off-label for the treatment of various dermatologic diseases (Table IV). Our clinical experience with MMF is presented and discussed in this section. The reliability and validity of our study would be enhanced if standard scoring measures had been used. However, we feel that sharing our experience will help generate more interest and research in an area

Future considerations

MMF is available currently for enteral and parenteral intravenous forms. The systemic reach of MMF is beneficial in the transplant field in order for MMF to prevent rejection. In several dermatologic conditions, such as those associated with DM, SLE, and other more extensive autoimmune disease, the systemic effects are also desired. However, in conditions limited to the skin, an effective topical form of MMF avoiding systemic side effects would be beneficial. Studies are currently investigating

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    Funding sources: None.

    Conflicts of interest: None declared.

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