TY - JOUR
T1 - Tolerability of sirolimus
T2 - A decade of experience at a single cardiac transplant center
AU - Thibodeau, Jennifer T.
AU - Mishkin, Joseph D.
AU - Patel, Parag C.
AU - Kaiser, Patricia A.
AU - Ayers, Colby R.
AU - Mammen, Pradeep P.A.
AU - Markham, David W.
AU - Ring, William Steves
AU - Peltz, Matthias
AU - Drazner, Mark H.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Adverse events
KW - Cardiac transplantation
KW - Immunosuppression
KW - Sirolimus
KW - Tolerability
UR - http://www.scopus.com/inward/record.url?scp=84889092059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84889092059&partnerID=8YFLogxK
U2 - 10.1111/ctr.12269
DO - 10.1111/ctr.12269
M3 - Article
C2 - 24304376
AN - SCOPUS:84889092059
SN - 0902-0063
VL - 27
SP - 945
EP - 952
JO - Clinical Transplantation
JF - Clinical Transplantation
IS - 6
ER -