Sirolimus (Rapamycin)

Sirolimus is a macrocyclic lactone (MW 914) produced by the actinomycete Streptomyces Hygroscopicus.  Sirolimus is an antiproliferative immunosuppressant which engages FKBP12 to create complexes that compete for the same intracellular binding protein FKBP12.Use of sirolimus has improved graft survival rates and decreased rejection incidence and severity. Sirolimus is more effective when used in combination with Cyclosporin A.  Sirolimus use has also permitted Cyclosporin A target-level reduction, thereby avoiding or minimizing nephrotoxicity secondary to calcineurin inhibitors. Adverse effects include hyperlipidemia (ie, elevated cholesterol, triglycerides), leukopenia, and thrombocytopenia.