Hypersensitivity reactions reported. Immunosuppressive agents, including sirolimus, increase risk of infection. Cases of interstitial lung disease (e.g. pneumonitis, bronchiolitis obliterans organizing pneumonia, pulmonary fibrosis) observed (risk may be increased with higher trough levels). Increased risk of fluid accumulation and lymphocele. Peripheral edema, lymphedema, and pleural and pericardial effusions reported. Immunosuppressive agents may be associated with development of lymphoma. Immunosuppressant therapy associated with increased risk of skin cancer. Increased urinary protein excretion observed when converting renal transplant patients from calcineurin inhibitors to sirolimus during maintenance therapy. May be associated with wound dehiscence and impaired healing (caution in perioperative period; patients with body mass index >30 kg/m^2^ are at increased risk for abnormal wound healing). Use with caution in hepatic impairment, and in hyperlipidemia (may increase serum lipids). Concurrent use with calcineurin inhibitor (cyclosporine, tacrolimus) may increase risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy. Use with caution in patients taking strong CYP3A4 inhibitors and moderate or strong CYP3A4 inducers or medications which may alter renal function. Sirolimus not recommended for use in de novo liver transplant patients (risk of hepatic artery thrombosis, graft failure, and increased mortality when sirolimus is used in combination with cyclosporine and/or tacrolimus). Sirolimus not recommended for use in de novo lung transplant patients (risk of bronchial anastomotic dehiscence). In renal transplant patients, de novo use without cyclosporine associated with higher rates of acute rejection.