title: Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.
abstract: Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Dallas, TX, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Thibodeau
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mishkin
authors.forename: Parag C
authors.initials: PC
authors.lastname: Patel
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kaiser
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Pradeep P A
authors.initials: PP
authors.lastname: Mammen
authors.forename: David W
authors.initials: DW
authors.lastname: Markham
authors.forename: William Steves
authors.initials: WS
authors.lastname: Ring
authors.forename: Matthias
authors.initials: M
authors.lastname: Peltz
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006331:Heart Diseases / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: adverse events; cardiac transplantation; immunosuppression; sirolimus; tolerability