sirolimus + cyclosporine + tacrolimus

Sirolimus + cyclosporine + tacrolimus is a combination of three potent immunosuppressive small molecules primarily used in the management of organ transplant recipients to prevent graft rejection. Sirolimus (also known as rapamycin) is an mTOR inhibitor that blocks IL-2-mediated T-cell proliferation by inhibiting the mechanistic target of rapamycin kinase. Cyclosporine and tacrolimus are calcineurin inhibitors (CNIs) that prevent T-cell activation by binding to specific immunophilins (cyclophilin A and FKBP12, respectively) and inhibiting the phosphatase activity of calcineurin, which in turn prevents the translocation of NFAT and the transcription of pro-inflammatory cytokines. In clinical practice, these agents are typically used in dual combinations (e.g., sirolimus paired with either tacrolimus or cyclosporine) rather than as a triple therapy, as the simultaneous use of both CNIs is generally avoided due to additive nephrotoxicity and overlapping mechanisms of action.

Other names

sirolimus + cyclosporine + tacrolimus