1 INDICATIONS AND USAGE
Sirolimus oral solution 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 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 oral solution is an mTOR inhibitor indicated for the treatment of patients with lymphangioleiomyomatosis (1.3).
1.1 Prophylaxis of Organ Rejection in Renal
Transplantation
Sirolimus oral solution 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sirolimus oral solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see Dosage and Administration (2.2)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 oral solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see Dosage and Administration (2.3)and
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 oral solution 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 oral solution 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)andClinical Studies (14.6)
].
The safety and efficacy of de novo use of sirolimus oral solution 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 oral solution in maintenance renal transplant patients have not been established [see Clinical Studies (14.4)
].
1.3 Treatment of Patients with
Lymphangioleiomyomatosis
Sirolimus oral solution is indicated for the treatment of patients with lymphangioleiomyomatosis (LAM).