Sirolimus hyperlipidemia with

The most striking consequence of treatment with sirolimus is dose-dependent hyperlipidemia with significant increases in both cholesterol and triglyceride serum concentrations, which resolve after dosage reduction or sirolimus withdrawal (1065). 

Sirolimus, a target of rapamycin inhibitor, works by decreasing the ability of T cells to respond to IL-2. The major adverse events associated with sirolimus are decreased wound healing, hyperlipidemia, and myelosuppression. This agent appears to have promising effects because it may allow calcineurin inhibitor withdrawal in some patients. 

The most common adverse events reported with sirolimus are leukopenia (20%), thrombocytopenia (13% to 30%), and hyperlipidemia (38% to 57%).11,31 Other adverse effects include delayed wound healing, anemia, diarrhea, arthralgias, rash, and mouth ulcers. Sirolimus has an FDA black-box warning in newly transplanted liver and lung recipients.11 In liver transplant recipients, use of sirolimus immediately after transplant is associated with an increased risk of hepatic artery thrombosis, graft loss, and death. In lung transplant... 

Renal transplant patients have a higher prevalence of clinically significant hyperlipidemia. Accordingly, carefully consider the risk/benefit in patients with established hyperlipidemia before initiating an immunosuppressive regimen including sirolimus. 

Sirolimus is an excellent immunosuppressant without apparent nephrotoxicity. The major problems with clinical use are delayed wound healing in some recipients and hyperlipidemia. 

In a 1-year follow-up of 40 renal transplant patients treated with various dosages of sirolimus (0.5-7 mg/m2/ day) in addition to a ciclosporin-based regimen, there were significant increases in serum cholesterol and triglycerides, and significant falls in white blood cell and platelet counts, compared with historical controls (1066). These effects correlated with sirolimus trough concentrations but not dosages. One patient had to discontinue sirolimus because of hyperlipidemia refractory to treatment. 

Hypertriglyceridemia due to sirolimus often does not respond to dosage reduction or hypolipidemic drugs. After liver transplantation (n — 6), significant hyperlipidemia improved after withdrawal of sirolimus (1070). The incidence of sirolimus-associated hyperlipidemia is up to 44%. After liver transplantation, there was hypercholesterolemia in 15% and hypertriglyceridemia in 10% of recipients. Sirolimus in combination with tacrolimus... 

Brattstrom C, Wilczek H, Tyden G, Bottiger Y, Sawe J, Groth CG. Hyperlipidemia in renal transplant recipients treated with sirolimus (rapamycin). Transplantation 1998 65(9) 1272 1. 

Sirolimus exerts its activity by inhibiting T-cell response to IL-2. The adverse effects associated with sirolimus include thrombocytopenia, anemia, and hyperlipidemia. 

Observational studies In a single-center study in 86 liver transplant recipients taking sirolimus, eight had too short a follow-up to include them in the analysis of long-term results, 38 were treated with sirolimus as the main immunosuppressant, and the other 40 took sirolimus-I-caldneurin inhibitors [124. Of the 86 patients, 82 developed a total of 92 adverse reactions hyperlipidemia ( =44), leg edema ( =20), anemia ( = 12), oral ulcers (n=5), rashes (n=5), diarrhea and leukopenia (two each), and thrombocytopenia and cardiomyopathy (one each). Sirolimus was withdrawn because of severe adverse reactions in seven cases, including generalized rashes (n=3), and cardiomyopathy, leg edema, diarrhea, anemia, and oral ulcers (one each). Rashes and cardiomyopathy developed soon after sirolimus introduction, the other adverse reactions usually had a gradual onset of several months. The leg edema in 20 patients resolved spontaneously in 7,... 

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