Mycophenolate mofetil: a review of its use in the management of solid organ transplantation

Mycophenolate mofetil is the morpholinoethyl ester prodrug of mycophenolic acid, an uncompetitive reversible inhibitor of the rate-limiting enzyme in de novo purine synthesis, inosine monophosphate dehydrogenase. As an antimetabolite immunosuppressant, mycophenolate mofetil has been evaluated for the prevention and treatment of acute rejection of a variety of solid organ allografts. It is generally added to post-transplant therapy regimens in place of azathioprine, and in conjunction with cyclosporin and corticosteroids. In large, randomised controlled trials in renal and cardiac transplant recipients, mycophenolate mofetil has shown significant efficacy in reducing the incidence of acute rejection compared with azathioprine in the first year after transplantation. Whereas patient and graft survival rates are improved with mycophenolate mofetil in cardiac transplantation, significant benefits for patient or graft survival have not been demonstrated in clinical trials in renal transplant patients. Mycophenolate mofetil does, however, appear to reduce the incidence of renal graft loss due to rejection. Mycophenolate mofetil has been shown to reverse ongoing acute rejection episodes in heart, kidney and liver transplant patients, and to improve graft function when used to treat chronic lung or heart graft vasculopathy. The efficacy of mycophenolate mofetil immunosuppression appears to allow sparing of other immunosuppressive agents, particularly cyclosporin and corticosteroids, in selected patients. The main adverse effects associated with oral mycophenolate mofetil are GI events, haematological toxicity (especially leucocytopenia) and an increased incidence of some types of infections relative to placebo. Lower dosages (2 g/day) are generally better tolerated than higher dosages (3 g/day). Although mycophenolate mofetil carries a high acquisition cost relative to azathioprine, when other direct costs of treatment of organ transplant patients are considered, it appears to be a cost-effective alternative, at least during the first post-transplant year.

The benefits in terms of a reduction in the morbidity associated with acute organ allograft rejection indicate that mycophenolate mofetil should be considered as part of a primary therapy regimen in renal and cardiac transplant recipients, and as a treatment for reversal of acute refractory rejection in these patients. Further study is required to confirm its benefits in the transplantation of other solid organs.