Professional Documents
Culture Documents
696 1398 1 SM PDF
696 1398 1 SM PDF
Review Article
Mycophenolate mofetil: a new therapeutic
option in dermatology
Atif Shehzad, Muhammad Azam Bokhari, Saira Shaheen
Abstract Mycophenolic acid (MPA) was introduced in the 1970s as a treatment for psoriasis, it has
since been reformulated as mycophenolate mofetil (MMF). With an improved side effect
profile and enhanced bioavailability, MMF is a promising drug for immune-mediated skin
diseases. It is currently approved for the prevention of organ rejection. Its list of
dermatological indications continues to grow. As a noncompetitive inhibitor of inosine
monophosphate dehydrogenase (IMPDH), MMF inhibits de novo purine synthesis. Its
relative lack of hepatonephrotoxicity and perhaps low risk of carcinogenicity offer important
therapeutic advantages. This new formulation showed enhanced bioavailability, tolerability
and efficacy. No doubt case reports and case series of MMF therapy dominate the
dermatologic literature; preliminary results are sufficiently promising to warrant larger,
randomized clinical trials with this emerging therapy.
Key words
Mycophenolate mofetil, inosine monophosphate dehydrogenase, dermatology.
In the past two decades, an increasing In 1995, MMF received FDA approval for
number of immunosuppressive agents have prevention of acute renal allograft rejection
been developed to prevent allograft rejection and was recognized as an effective treatment
in organ transplantation. A number of these option for immune-mediated skin diseases.
medications have shown therapeutic efficacy
in inflammatory skin diseases. Structure
Mycophenolic acid (MPA) was first
recognized as a lipid soluble weak organic Mycophenolate mofetil is the semi-
acid, isolated from cultures of Penicillium synthetic 2-morpholinoethyl ester of MPA.
stoloniferum.1 It was later shown to have The chemical name for MMF is 2-
antibacterial, antiviral, antifungal, morpholinoethyl (E)-6-(1, 3-dihydro-4-
antitumoral and immunosuppressive hydroxy-6-methoxy-7-methyl-3-oxo-5-
2-7
properties. In 1975, MPA demonstrated isobenzofuranyl)-4-methyl-4-hexenoate
(Figure 1). It has an empirical formula of
Address for correspondence C23H31NO7.9
Dr. Atif Shehzad
Senior Registrar,
Department of Dermatology, Mechanism of action
Services Institute of Medical Sciences/
services hospital, Lahore. Mycophenolate mofetil selectively and
Ph # +92 300 4326570
E-mail: dratifshehzad@hotmail.com noncompetitively inhibits inosine
105
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
O OH CH3
OCH3
CH3
Figure 1 Chemical structure of mycophenolate mofetil.
Mycophenolate mofetil also prevents the Potential indications are listed in Table 1,
glycosylation of lymphocytes and monocyte and selected dermatoses are reviewed below.
glycoprotein that are involved in adhesion to
endothelial cells. It further inhibits the Psoriasis
recruitment of leukocytes to sites of Multiple case reports suggest that MMF is
inflammation and impairs antigen an effective treatment option for psoriasis.13-
11 17
presentation. It does not inhibit early In a study of 11 patients with stable plaque
events in the activation of human peripheral type psoriasis, the efficacy of MMF was
blood mononuclear cells (IL-1 and IL-2 measured using the psoriasis area and
production), but blocks the coupling of these severity index (PASI) score.18 Patients
events to DNA synthesis and proliferation.10 initially received MMF 1g twice daily for 3
weeks followed by 0.5g twice daily. Within
3 weeks of therapy, there was a reduction in
106
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
107
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
108
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
The long term risk of carcinogenicity with Possible drug interactions with MMF are
MMF remains controversial. shown in Table 2.
Lymphoproliferative disease or lymphoma
developed in 0.4%-1% of patients receiving Conclusion
MMF with other immunosuppressive agents
for renal, cardiac and hepatic Mycophenolate mofetil has been
transplantation.31 These patients were successfully used both in combinations with
followed for > 1 year. Non melanoma skin systemic steroids and as monotherapy in a
cancer occurred in 1.6%-4.2% of patients, variety of inflammatory skin disorders.
while other types of malignancies appeared Early reports on efficacy and tolerability
in 0.7%-2.1% of patients.31 Three-year show that MMF offer hope to patients with
safety data in renal and cardiac transplant immune-mediated skin diseases. Its safety
patients failed to reveal any changes in the profile appears reassuring. Randomized
incidence of malignancy.31 clinical trials with long surveillance periods
are warranted to validate the efficacy and
As a noncompetitive inhibitor of purine safety of MMF in the treatment of
synthesis, MMF fails to initiate dermatologic diseases.
chromosomal breaks, which makes it less
carcinogenic.32 References
109
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
110
Journal of Pakistan Association of Dermatologists 2007; 17: 105-111.
Erratum
In the Original article entitled ‘Long-pulsed Nd:YAG laser and intense pulse light therapy
for idiopathic facial hirsutism. A comparative study’ by Tahir Kamal published in the
(JPAD 2006; 16: 205-9.), it is clarified by the author that out of 100 patients included in
the study, 23 were recruited from the out-patient clinic of dermatology department of
Jinnah Hospital, Lahore; however, all were treated with laser or intense pulse light at a
private clinic.
111