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 months to 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 tablets are 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that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see Dosage and Administration (2.2)].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 tablets 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 tablets 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 tablets 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 tablets 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 tablets in maintenance renal transplant patients have not been established [see Clinical Studies (14.4)].
1.3 Treatment of Patients with Lymphangioleiomyomatosis
Sirolimus tablets are indicated for the treatment of patients with lymphangioleiomyomatosis (LAM).