Sirolimus

What it is and how it works

Mechanism of Action Sirolimus inhibits T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin [IL]-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus: FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian target of rapamycin (mTOR), a key regulatory kinase.

Mechanism class: mTOR Inhibitors · Protein Kinase Inhibitors

Indications

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 . Patients at high-immunologic risk: Use in combination with CsA and corticosteroids for the first 12 months following transplantation . 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 . 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.

Dosage and administration (summary)

Sirolimus Oral Solution is to be administered orally once daily, consistently with or without food . Renal Transplant Patients: Administer once daily by mouth, consistently with or without food . Administer the initial dose as soon as possible after transplantation and 4 hours after CsA ( 2.1 , 7.1 ). Adjust the sirolimus maintenance dose to achieve sirolimus trough concentrations within the target-range . Hepatic impairment: Reduce maintenance dose in patients with hepatic impairment ( 2.7 , 8.6 , 12.3 ). In renal transplant patients at low-to moderate-immunologic risk: Sirolimus and CsA Combination Therapy: One loading dose of 6 mg on day 1, followed by daily maintenance doses of 2 mg .

Contraindications

Sirolimus Oral Solution is contraindicated in patients with a hypersensitivity to sirolimus [ see Warnings and Precautions ]. Hypersensitivity to sirolimus .

Warnings and precautions

Hypersensitivity Reactions Angioedema Fluid Accumulation and Impairment of Wound Healing Hyperlipidemia Decline in Renal Function Proteinuria Latent Viral Infections Interstitial Lung Disease/Non-Infectious Pneumonitis De Novo Use Without Cyclosporine Increased Risk of Calcineurin Inhibitor-Induced Hemolytic Uremic Syndrome/ Thrombotic Thrombocytopenic Purpura/ Thrombotic Microangiopathy Embryo-Fetal Toxicity: Can cause fetal harm.

Pregnancy

Pregnancy Risk Summary Based on animal studies and the mechanism of action, Sirolimus can cause fetal harm when administered to a pregnant woman [ see Data , Clinical Pharmacology ]. There are limited data on the use of sirolimus during pregnancy.

Storage and supply

Since sirolimus is not absorbed through the skin, there are no special precautions. However, if direct contact of the oral solution occurs with the skin or eyes, wash skin thoroughly with soap and water; rinse eyes with plain water. Do not use Sirolimus Oral Solution after the expiration date.

Source: Sirolimus (Sirolimus) — US FDA prescribing information, 2024-04-30, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.