sirolimus

1 INDICATIONS AND USAGE Sirolimus is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants: • Patients at low- to moderate-immunologic risk: Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2–4 months after transplantation ( 1.1 ). • Patients at high-immunologic risk: Use in combination with CsA and corticosteroids for the first 12 months following transplantation ( 1.1 ). Safety and efficacy of CsA withdrawal has not been established in high risk patients ( 1.1 , 1.2 , 14.3 ). Sirolimus is an mTOR inhibitor indicated for the treatment of patients with lymphangioleiomyomatosis ( 1.3 ). 1.1 Prophylaxis of Organ Rejection in Renal Transplantation Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low- to moderate-immunologic risk, it is recommended that sirolimus be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [ see Dosage and Administration (2.2) ]. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level >80%]), it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first year following transplantation [ see Dosage and Administration (2.3) , Clinical Studies (14.3) ]. 1.2 Limitations of Use in Renal Transplantation Cyclosporine withdrawal has not been studied in patients with Banff Grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, those with serum creatinine >4.5 mg/dL, Black patients, patients of multi-organ transplants, secondary transplants, or those with high levels of panel-reactive antibodies [ see Clinical Studies (14.2) ]. In patients at high-immunologic risk, the safety and efficacy of sirolimus used in combination with cyclosporine and corticosteroids has not been studied beyond one year; therefore after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient [ see Clinical Studies (14.3) ]. In pediatric patients, the safety and efficacy of sirolimus have not been established in patients <13 years old, or in pediatric (<18 years) renal transplant patients considered at high-immunologic risk [ see Adverse Reactions (6.5) , Clinical Studies (14.6) ]. The safety and efficacy of de novo use of sirolimus without cyclosporine have not been established in renal transplant patients [ see Warnings and Precautions (5.12) ]. The safety and efficacy of conversion from calcineurin inhibitors to sirolimus in maintenance renal transplant patients have not been established [ see Clinical Studies (14.4) ]. 1.3 Treatment of Patients with Lymphangioleiomyomatosis Sirolimus is indicated for the treatment of patients with lymphangioleiomyomatosis (LAM).