Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management

Mycophenolate mofetil (MMF) is a relatively new immunosuppressive drug. It inhibits inosine monophosphate dehydrogenase, a key enzyme in the de novo pathway of purine synthesis, and thus causes lymphocyte-selective immunosuppression. Large clinical trials have revealed the efficacy of MMF in the prevention of allograft rejection when administered together with cyclosporin or tacrolimus and corticosteroids. Although the adverse effect profile of MMF is comparatively benign, gastrointestinal adverse effects are a major concern. These effects are partially explained by the increased immune suppression, by the mode of action and by interactions, particularly with other immunosuppressants. The aetiology of the rarest gastrointestinal adverse effects is still not completely clear. Therapy depends upon the clinical gravity of the adverse effects and is therefore a case of waiting and ob- serving. An adjustment of dosage of immunosuppressants according to the clinical situation and, particularly in the case of MMF, spreading the total dosage over more than 2 daily doses are often sufficient. Should adverse effects persist for a longer period of time and be of a more serious nature, a comprehensive invasive diagnostic process is necessary, including endoscopy and biopsy and the search for opportunistic infections. In this case, dosage reduction or the complete withdrawal of MMF seems to be unavoidable. Severe gastrointestinal complications with MMF are rare, but when they do occur they may require extensive diagnosis and treatment. In the future, therapeutic drug monitoring and, where necessary, pharmacological modifications of MMF could lead to a further reduction of adverse effects with an equal or even increased efficacy.