Gastrointestinal side effects of mycophenolate mofetil compared to mycophenolic acid in renal transplant patients

Background: Wide range of immunosuppressive (IS) drugs is available to prevent acute rejection after renal transplantation (RTX). Mycophenolic acid blocks de novo purin synthesis. This drug is not nephrotoxic, and prevents chronic rejection. There are two drug types available: I. mycophenolate mofetil (MMF) and II. enteric coated mycophenolic acid sodium (MPA). Gastrointestinal side effects often lead to dose reduction or drug withdrawal.

Patients and methods: Authors analysed data retrospective of patients underwent RTX and received either MMF or MPA in combination with calcineurin inhibitor type or antiproliferative IS drugs. Part of the recipient population participated in international double blind comparative studies of these drugs. GI and haematological side effects, conversion and dose adjustment or withdrawal has been examined. Results: 320 renal recipients were treated from 11.1997. to 11.2005. 200 (62,2%) patients received MMF, while 34 (10,6%) received MPA. (MPA is only available since 2004.) In 83 (25,9%) of patients one or both drugs were not tolerated, which lead to drug withdrawal. Dose adjustment was required in 76 patients (40%) in the MMF and 8 (23,5%) in the MPA group. The most common cause of intolerance was GI side effects (83,7%), mainly nausea, vomiting, colic and diarrhoea. In one case, severe fulminant toxic colitis occurred and caused death. Histology revealed loss of IBD, invasive infection or vascular disorder, and the correlation between MMF and colitis is highly probable. Discussion: GI intolerance of MMF and MPA limits therapeutic exposure. Dose adjustment or drug withdrawal may be necessary. Accurate diagnostic of specific drug related GI side effects is difficult in the early postoperative period, regarding the simultaneous use of several IS drugs, antibiotics, sudden changes in body fluid volume and ion transport. In later post transplant period, MMF or MPA related side effects seem to be diagnosed easier. The most important points are to exclude microbial diarrhoea, dietary mistakes, internal diseases, steroid side effects. In this set of circumstances, MPA was tolerable to a better extent in RTX patients, hopefully contributing to long graft survival in this subgroup.