EC-MPS permits lower gastrointestinal symptom burden despite higher MPA exposure in patients with severe MMF-related gastrointestinal side-effects.
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.
Sabbatini
Massimo
M
Department of Nephrology, Day-Hospital of Renal Transplantation, University Federico II, Naples, Italy.
Capone
Domenico
D
Gallo
Riccardo
R
Pisani
Antonio
A
Polichetti
Giuliano
G
Tarantino
Giovanni
G
Gentile
Antonio
A
Rotaia
Eliana
E
Federico
Stefano
S
D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013608:Tablets, Enteric-Coated
D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid