Organ rejection, prophylaxis

Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers. The PDA has recently approved everolimus for organ rejection prophylaxis on April 22, 2010. A Phase II trial reports it is effective in the treatment of subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis. In Oct 2010, the PDA approved its use in SEGA unsuitable for surgery. As of Oct 2010 Phase III trials are under way in breast cancer, gastric cancer, hepatocellular carcinoma, pancreatic neuroendocrine tumors (NET), and lymphoma. ... 

Organ rejection prophylaxis Prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. It is recommended that tacrolimus be used concomitantly with adrenal corticosteroids. Because of the risk of anaphylaxis, reserve the injection for patients unable to take the capsules orally. 

Organ rejection Prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that sirolimus be used in a regimen with cyclosporine and corticosteroids. In patients at low to moderate immunological risk, cyclosporine should be withdrawn 2 to 4 months after transplantation and sirolimus dose should be increased to reach recommended blood concentrations. 

Organ rejection, prophylaxis Prophylaxis of acute organ rejection in patients receiving renal transplants. It is used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. 

The use of SRL has transcended from organ rejection prophylaxis to applications in medical devices owing to its effects of inhibiting lymphocyte and smooth muscle cell proliferation, which translate into suppression of neointimal hyperplasia [5]. Example devices include coronary artery stents, some of which are approved for patient care, and... 

Sirolimus (rapamycin) (Vezina et al. 1975) is widely used to prevent rejection in organ transplant. It is especially usefiil in kidney transplants because, different from cyclosporine and tacrolimus, it is not a calcineurin inhibitor and therefore is less toxic to the kidney. Sirolimus inhibits T-cell and B-cell activation. It binds to the immunophilin FKproteinl2, and this binary complex inactivates a serine-threonine kinase (mTOR) termed the mammalian target of rapamycin (Huang et al. 2003). The final effect is the arrest at phase G1 of cell cycle progression. This effect occurs not only in T cell and B cells, but it has been observed in many tumor cell lines. Semisynthetic derivatives of rapamycin, suitable for i.v. administration, have been developed as antitumor agents. Temsirolimus was approved by FDA in 2007 for advanced kidney cancer treatment (Hudes 2009). Everolimus was also approved for kidney cancer treatment in 2009 and for organ rejection prophylaxis in 2010. At present, phase III clinical trials are under way in a variety of tumors (Dansey 2006). 

Prophylaxis of acute organ rejection in allogeneic renal transplantation... 

Sirolimus is a calcineurin inhibitor that acts as an immunosuppressant. It is administered systemically in the prophylaxis of organ rejection in kidney allograft recipients. It may be used in combination with ciclosporin, particularly initially. However since ciclosporin is markedly nephrotoxic, when sirolimus is used with ciclosporin, monitoring of kidney function is essential. 

Renal, cardiac, and hepatic transplant Mycophenolate is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants. Use mycophenolate concomitantly with cyclosporine and corticosteroids. 

Allogeneic transplants For prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Gengraf and A/eora/have been used in combination with azathioprine and corticosteroids. Sanc//n n nne always is to be used with adrenal corticosteroids. Sandimmune a so may be used in the treatment of chronic rejection in patients previously treated with other immunosuppressive agents. Because of the risk of anaphylaxis, reserve Sandimmune injection for patients who are unable to... 

Mycophenolate mofetil is used together with cyclosporine and corticosteroids for the prophylaxis of acute organ rejection in patients undergoing allogeneic renal, or hepatic transplants. Compared with azathioprine it is more lymphocyte-specific and is associated with less bone marrow suppression, fewer opportunistic infections and lower incidence of acute rejection. More recently, the salt mycophenolate sodium has also been introduced. Mycophenolate mofetil is rapidly hydrolyzed to mycopheno-lic acid, its active metabolite. Mycophenolic acid is a reversible noncompetitive inhibitor of inosine monophosphate dehydrogenase, an important enzyme for the de novo synthesis of purines. As lymphocytes have little or no salvage pathway for purine... 

The prophylaxis of organ rejection in patients receiving renal transplants. ... 

Efficacious mAbs are used in a variety of therapeutic indications such as cancer, rheumatoid arthritis, Crohn s disease, psoriasis, organ transplantation, asthma, infectious diseases, and cardiovascular diseases, while for other diseases research and development is currently ongoing. The current three major therapeutic areas include oncology (eight mAbs against solid tumors and lymphoma/leukemia), inflammatory diseases (five mAbs), and the immunosuppression/prophylaxis or treatment of organ rejection in transplantation (three mAbs). The reader is referred to Chapter 12 for a detailed discussion on the exposure-response relationships and pharmacodynamics of therapeutically administered mAbs. 

Tacrolimus is indicated for prophylaxis of organ rejection in adult patients undergoing transplantation and to treat a variety of autoimmune diseases (Fung, 2004 Krensky et al., 2005 Spencer et al., 1997). 

Indications Prophylaxis of organ rejection in transplants Category Calcineurin inhibitor Disease-modifying antirheumatic Immunosuppressant Half-life 10-27 hours (adults)... 

Synonym mycophenolate mofetil Trade names CellCept (Roche) Myfortic (Novartis) Indications Prophylaxis of organ rejection Category Immunosuppressant TNF inhibitor Half-life 18 hours... 

Indications Prophylaxis of organ rejection in renal transplants Category Antibiotic, macrolide Immunosupressant Non-calcineurin inhibitor Half-life 62 hours... 

Indications Prophylaxis of organ rejection, atopic dermatitis (topical)... 

Simulect (Basiliximab chimeric mAb directed against the a chain of the IL-2 receptor) Novartis prophylaxis of acute organ rejection in allogeneic renal transplantation 1998 (EU and US)... 

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