Tacrolimus for the prevention and treatment of rejection of solid organ transplants

ABSTRACT

Since its introduction to the antirejection armamentarium in 1994, tacrolimus has become the workhorse of transplant professionals for avoidance of solid organ transplant rejection. Not only does tacrolimus have potent immunosuppressive qualities that prevent rejection, but dosing is straight forward and it is generally well tolerated. However, in the long term, conditions such as calcineurin inhibitor nephrotoxicity can become a problem. A discussion of the compound, the pharmacokinetics, history, and current approved uses for tacrolimus is described. Indeed, tacrolimus is the most important drug for preventing transplant rejection. However, the increased appreciation for significant side effects, particularly in the long term, has led to building interest in new agents with different mechanisms of action and different metabolism.

KEYWORDS:

• Transplant
• antirejection
• maintenance immunosuppression
• calcineurin inhibition

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Tacrolimus is the most important of the three commonly used agents for maintenance immunosuppression.

• Tacrolimus was pioneered by Dr. Tom Starzl.

• Tacrolimus may be used to treat rejection.

• Tacrolimus is associated with better rejection-free graft survival than is cyclosporine.

• Tacrolimus is more diabetogenic than cyclosporine.

• Belatacept, and/or other maintenance immunosuppressive agents that avoid nephrotoxicity, may replace calcineurin inhibitors in the coming years.

• Adverse effects of tacrolimus also include neurologic symptoms, metabolic complications, and dyslipidemia.

• The future of tacrolimus remains bright, but there are opportunities for improving the drug’s side effect profile.