title: Effect of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium on maximum tolerated dose and gastrointestinal symptoms following kidney transplantation.
abstract: Despite the potential tolerability advantage of enteric-coated mycophenolate sodium (EC-MPS), no prospective, randomized trial has evaluated whether conversion from mycophenolate mofetil (MMF) to EC-MPS permits mycophenolic acid dose to be increased or gastrointestinal side-effects to be ameliorated. In a randomized, multicenter, open-label trial, kidney transplant recipients experiencing gastrointestinal side-effects either remained on MMF or switched to an equimolar dose of EC-MPS, adjusted 2 weeks subsequently to target the highest tolerated dose up to 1440 mg/day (EC-MPS) or 2000 mg/day (MMF). Patients were followed up to 12 weeks postrandomization. One hundred and thirty-four patients were randomized. The primary efficacy endpoint, the proportion of patients receiving a higher mycophenolic acid (MPA) dose at week 12 than at randomization, was significantly greater in the EC-MPS arm (32/68, 47.1%) than the MMF arm (10/61, 16.4%; P < 0.001). At the final visit, 50.0% (34/68) of EC-MPS patients were receiving the maximum recommended dose versus 26.2% (16/61) of MMF patients (P = 0.007). Kidney transplant patients receiving reduced-dose MMF because of gastrointestinal side-effects can tolerate a significant increase in MPA dose after conversion to EC-MPS. Patient-reported gastrointestinal outcomes with higher doses of EC-MPS remained at least as good as in MMF-treated controls.
authors.affiliation: Transplant Unit, Nottingham University Hospital, City Hospital Campus, Hucknall Road, Nottingham, UK. m_shehata@mac.com
authors.forename: Magdi
authors.initials: M
authors.lastname: Shehata
authors.forename: Sunil
authors.initials: S
authors.lastname: Bhandari
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkat-Raman
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Richard
authors.initials: R
authors.lastname: D'Souza
authors.forename: Hany
authors.initials: H
authors.lastname: Riad
authors.forename: Ali
authors.initials: A
authors.lastname: Bakran
authors.forename: Richard
authors.initials: R
authors.lastname: Baker
authors.forename: Christine
authors.initials: C
authors.lastname: Needham
authors.forename: Christopher
authors.initials: C
authors.lastname: Andrews
mesh_terms: D000328:Adult; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013608:Tablets, Enteric-Coated
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid