What is the role of tacrolimus in immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Answer

Tacrolimus

Tacrolimus is a macrolide antibiotic and is active against helper T cells, preventing the production of IL-2 via calcineurin inhibition (binds to tacrolimus-binding protein instead of cyclophilin protein). The tacrolimus:FKBP12 active complex inhibits calcineurin with greater potency than the corresponding cyclosporine complex. This agent is used for maintenance immunosuppression and for rescue therapy in patients with refractory rejection under cyclosporine-based therapy.

Multiple drug interactions are possible, primarily with agents affecting the cytochrome P-450 system. One study evaluated the long-term safety and efficacy of tacrolimus in orthotopic liver transplantation (OLT). The study reviewed 1000 primary OLTs performed between August 1989 and December 1992 and maintained with tacrolimus-based immunosuppression therapy. After 17- to 20-year follow-up, the results found patient survival rates at 35.8% and graft survival rates at 32.6%, with significantly better survival among children. Graft loss was attributed to age-related complications, recurrence of primary disease, and malignancy; rarely was graft loss related to immunologic reasons. The data conclude that tacrolimus is a potent immunosuppressive agent in OLT.

Adverse effects are similar to those of cyclosporine but with a lower incidence of hypertension, hyperlipidemia, skin changes, hirsutism, and gum hyperplasia and a higher incidence of new-onset diabetes mellitus after transplantation (NODAT) and neurotoxicity. Although tacrolimus causes less cosmetic effects than cyclosporine, it can cause reversible alopecia.


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