Continuing medical educationMycophenolate 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
References (172)
- et al.
Mycophenolic acid—an antibiotic from Penicillium brevicompactum
Lancet
(1946) - et al.
Treatment of psoriasis with oral mycophenolic acid
J Invest Dermatol
(1975) - et al.
A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endoint in the assessment of psoriasis
J Am Acad Dermatol
(2004) - et al.
Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil
J Am Acad Dermatol
(2000) - et al.
Mycophenolate mofetil: a new therapeutic option in the treatment of blistering autoimmune diseases
J Am Acad Dermatol
(1999) - et al.
Bullous pemphigoid treated with mycophenolate mofetil
Lancet
(1997) - et al.
Mycophenolate mofetil in autoimmune and inflammatory skin disorders
J Am Acad Dermatol
(1999) - et al.
Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid-sparing agent
J Am Acad Dermatol
(2001) - et al.
The treatment of atopic dermatitis with systemic immunosuppressive agents
Clin Dermatol
(2003) - et al.
Treatment of resistant discoid lupus erythematosus of the palms and soles with mycophenolate mofetil
J Am Acad Dermatol
(2001)
The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus
J Invest Dermatol
Severe scleritis and urticarial lesions
Am J Ophthalmol
Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease
Chest
Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease
Chest
Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease
Respir Med
Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning
Biol Blood Marrow Transplant
A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogenic hematopoietic cell transplantation
Biol Blood Marrow Transplant
Treatment of severe lichen planus with mycophenolate mofetil
J Am Acad Dermatol
Rescue therapy with mycophenolate mofetil in refractory uveitis
Lancet
Contribution to the study of maize deterioration; biochemical and toxicological investigations of Penicillium puberulum and Penicillium stoloniferum
Bull Burl Anim Ind US Dept Agr
In vitro antiviral activity of mycophenolic acid and its reversal by guanine-type compounds
Appl Microbiol
Immunosuppressive effect of mycophenolic acid
J Antibiot (Tokyo)
Mycophenolic acid in the treatment of psoriasis: long-term administration
Arch Dermatol
Mycophenolate mofetil: a dermatologic perspective
Skin Therapy Lett
Bioavailability improvement of mycophenolic acid through amino ester derivatization
Pharm Res
Mycophenolate mofetil (CellCept) product information [CD-ROM]
Clinical pharmacokinetics of mycophenolate mofetil
Clin Pharmacokinet
Pharmacokinetic principles of immunosuppressive drugs
Am J Transplant
Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF)
Clin Transplant
Immunosuppressive and other effects of MPA and an esther prodrug, mycophenolate mofetil
Immunol Rev
Azathioprine in dermatology: the past, the present, and the future
J Am Acad Dermatol
Psoriasis vulgaris treated successfully with mycophenolate mofetil
Br J Dermatol
Mycophenolate mofetil as a systemic antipsoriatic agent: positive experience in 11 patients
Br J Dermatol
Change of treatment from cyclosporin to mycophenolate mofetil in severe psoriasis
Br J Dermatol
Sequential study on the treatment of moderate-to-severe chronic plaque psoriasis with mycophenolate mofetil and cyclosporin
J Eur Acad Dermatol Venereol
Mycophenolate mofetil (CellCept) for psoriasis: a two-center prospective open-label clinical trial
J Cutan Med Surg
Plasma trough levels of mycophenolic acid do not correlate with efficacy and safety of mycophenolate mofetil in psoriasis
Br J Dermatol
Topical application of mycophenolate mofetil in plaque-type psoriasis
Br J Dermatol
Autoimmune bullous dermatoses: a review
Am Fam Physician
Management of bullous pemphigoid: recommendations for immunomodulatory treatments
Am J Clin Dermatol
Treatment of pemphigus vulgaris with mycophenolate mofetil as a steroid-sparing agent
Eur J Dermatol
Treatment of pemphigus vulgaris and bullouos pemphigoid with mycophenolate mofetil monotherapy
Arch Dermatol
An evaluation of the usefulness of mycophenolate mofetil in pemphigus
Br J Dermatol
Mycophenolate mofetil as adjuvant in pemphigus vulgaris
Indian J Dermatol Venereol Leprol
A comparison of oral methylprednisone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus
Arch Dermatol
A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid
Arch Dermatol
Childhood IgA-mediated epidermolysis bullosa acquisita responding to mycophenolate mofetil as a corticosteroid-sparing agent
J Am Acad Dermatol
Mycophenolate mofetil as an adjuvant therapy for classic and endemic pemphigus foliaceus
J Dermatol
Successful long-term treatment of severe atopic dermatitis with mycophenolate mofetil
Br J Dermatol
Mycophenolate mofetil is effective in the treatment of atopic dermatitis
Arch Dermatol
Cited by (107)
Existing and Investigational Medications for Refractory Chronic Spontaneous Urticaria: Safety, Adverse Effects, and Monitoring
2022, Journal of Allergy and Clinical Immunology: In PracticeGlucocorticoids, Cyclosporine, Azathioprine, Chlorambucil, and Mycophenolate in Dogs and Cats: Clinical Uses, Pharmacology, and Side Effects
2022, Veterinary Clinics of North America - Small Animal PracticeOnset of acquired haemophilia A after omalizumab treatment in severe bullous pemphigoid – a report on two cases successfully treated with mycophenolate mofetil
2021, Annales de Dermatologie et de VenereologieHematologic Toxicity of Drug Therapy
2020, Comprehensive Dermatologic Drug Therapy, Fourth EditionMycophenolates
2020, Comprehensive Dermatologic Drug Therapy, Fourth Edition
Funding sources: None.
Conflicts of interest: None declared.