Pancreas Transplantation Medication

All pancreas transplant recipients require life-long immunosuppression to prevent a T-cell alloimmune rejection response. The Food and Drug Administration (FDA) has approved several new immunosuppressive agents, and several others currently are in clinical trials.

Two broad classifications of immunosuppressive agents exist—intravenous induction/antirejection agents and maintenance immunotherapy agents. No consensus exists as to the single best immunosuppressive protocol, and each transplant program utilizes various combinations of agents slightly differently.

The goals are to prevent acute or chronic rejection, minimize drug toxicity, minimize rates of infection and malignancy, and achieve the highest possible rates of patient and graft survival.

Class Summary

Induction immunotherapy consists of a short course of intensive treatment with intravenous agents. Antilymphocyte antibody induction therapeutic agents are varied and include polyclonal antisera, mouse monoclonals, and so-called humanized monoclonals. Polyclonal antisera, such as antilymphocyte globulin (ALG), antilymphocyte serum (ALS), and antithymocyte globulin (ATG) are equine, goat, or rabbit antisera directed against human lymphoid cells. The effects significantly lower and almost abolish circulating lymphoid cells critical to rejection response.

The agents are very effective at prophylaxis against early acute rejection, which is especially beneficial in managing the recipient with delayed graft function. The agents provide an effective immunologic cover during a period where the calcineurin inhibitors either are delayed or administered in subtherapeutic doses until graft function improves. Induction agents are used less often if immediate graft function occurs, such as recipients of living kidney donors, especially HLA-ID grafts.

Basiliximab (Simulect)

Chimeric monoclonal antibody that specifically binds to and blocks the IL-2 receptor on the surface of activated T cells.

Antithymocyte globulin, rabbit (Thymoglobulin)

A purified immunoglobulin solution produced by the immunization of rabbits with human thymocytes is used to treat acute rejection.

Alemtuzumab (Campath)

A humanized monoclonal antibody against the CD52 antigen. The anti-CD52 antibody induces lympholysis from complement-mediated lysis or other effector mechanisms.

Class Summary

Several immunosuppressive agents currently are in use for maintenance immunotherapy in kidney transplant recipients. Optimal maintenance immunosuppressive protocol has not been developed. Maintenance immunosuppressive agents are required for life.

Prednisone (Sterapred)

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Azathioprine (Imuran)

Active component of azathioprine is 6-mercaptopurine. Acts as purine analog that interacts with DNA and inhibits lymphocyte cell division.

Mycophenolate (CellCept, Myfortic)

Inhibitor of enzyme inosine monophosphate dehydrogenase (IMPDH). Results in inhibition of lymphocyte proliferation. Used for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

Cyclosporine (Sandimmune, Neoral)

Calcineurin inhibitors that diminish IL-2production in activated T cells. These agents bind to the intracellular immunophilin cyclophilin, interfering with the action of calcineurin, which inhibits nuclear translocation of the nuclear factor of activated T cells (NFAT).

Tacrolimus (Prograf)

Calcineurin inhibitor that diminishes IL-2 production in activated T cells. Binds to intracellular immunophilin, FKBP, interfering with the action of calcineurin, which inhibits nuclear translocation of the NFAT. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

Sirolimus (Rapamune)

Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP to block action of mTOR. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.