title: Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.
abstract: BACKGROUND
  There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events.
  
  
  METHODS
  The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up.
  
  
  RESULTS
  No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035).
  
  
  CONCLUSIONS
  Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.
authors.affiliation: University of British Columbia and the BC Transplant Society, Vancouver, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Cole
authors.forename: P
authors.initials: P
authors.lastname: Keown
authors.forename: D
authors.initials: D
authors.lastname: Landsberg
authors.forename: P
authors.initials: P
authors.lastname: Halloran
authors.forename: A
authors.initials: A
authors.lastname: Shoker
authors.forename: D
authors.initials: D
authors.lastname: Rush
authors.forename: J
authors.initials: J
authors.lastname: Jeffrey
authors.forename: D
authors.initials: D
authors.lastname: Russell
authors.forename: C
authors.initials: C
authors.lastname: Stiller
authors.forename: N
authors.initials: N
authors.lastname: Muirhead
authors.forename: L
authors.initials: L
authors.lastname: Paul
authors.forename: J
authors.initials: J
authors.lastname: Zaltzman
authors.forename: R
authors.initials: R
authors.lastname: Loertscher
authors.forename: P
authors.initials: P
authors.lastname: Daloze
authors.forename: R
authors.initials: R
authors.lastname: Dandavino
authors.forename: A
authors.initials: A
authors.lastname: Boucher
authors.forename: P
authors.initials: P
authors.lastname: Handa
authors.forename: J
authors.initials: J
authors.lastname: Lawen
authors.forename: P
authors.initials: P
authors.lastname: Belitsky
authors.forename: P
authors.initials: P
authors.lastname: Parfrey
authors.forename: A
authors.initials: A
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Hendricks
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure; D002170:Canada; D003141:Communicable Diseases / Q000453:epidemiology; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D011183:Postoperative Complications / Q000139:chemically induced / Q000145:classification / Q000453:epidemiology*; D011446:Prospective Studies; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D004655:Emulsions; D016572:Cyclosporine