EC-MPS permits lower gastrointestinal symptom burden despite higher MPA exposure in patients with severe MMF-related gastrointestinal side-effects

Fundam Clin Pharmacol. 2009 Oct;23(5):617-24. doi: 10.1111/j.1472-8206.2009.00711.x. Epub 2009 Jul 28.

Abstract

Gastrointestinal (GI) adverse events in renal transplant patients are a common cause of mycophenolate mofetil (MMF) dose reductions, which result in an increased risk of graft rejection because of a low immunosuppression. This study investigated whether conversion from MMF to enteric-coated mycophenolate sodium (EC-MPS) in renal transplant patients with serious GI side-effects, alleviated these symptoms and allowed administration of higher doses of EC-MPS. Nineteen renal transplant patients with severe MMF-related GI side-effects underwent a progressive reduction in MMF dose until symptoms disappeared. At this point, 12-h AUC(MMF) was evaluated and patients were shifted to an equimolar dose of EC-MPS. The EC-MPS dose was then progressively increased until the highest recommended dose was reached or GI symptoms re-appeared. Four weeks post-conversion, AUC(EC-MPS) was determined. Conversion led to a mean increase in EC-MPS dose of 68% (P < 0.0001), with a corresponding rise in AUC(0-12) (60.5%, P < 0.0006) associated with significant benefits in terms of both quality of life (Kidney Transplant Questionnaire, P < 0.01) and GI symptoms (Gastrointestinal Symptom Rating Scale, P < 0.0001), using validated questionnaires. In five of 19 patients, the EC-MPS dose could not be increased because of the prompt insurgence of GI symptoms. Renal function and biochemical parameters remained stable post-conversion and no rejection episodes occurred. These findings suggest that, in selected patients, EC-MPS may be better tolerated than MMF when GI symptoms are particularly important and permits higher mycophenolic acid exposure, when required.

Publication types

  • Clinical Trial

MeSH terms

  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / prevention & control*
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use
  • Quality of Life
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Tablets, Enteric-Coated

Substances

  • Immunosuppressive Agents
  • Tablets, Enteric-Coated
  • Mycophenolic Acid