Immunosuppressive pharmacotherapy in liver transplantation
The discovery of effective immunosuppressive medications, namely cyclosporine in the early 80’s, was the seminal event that dramatically improved patient and graft survival after liver transplantation and solidified its status as the treatment of choice for end-stage liver disease (ESLD). Over the ensuing 30 years, the immunosuppressive armamentarium has expanded dramatically leading to a significant decrease in acute cellular rejection (ACR), and hence improvements in graft and patient survival. Unfortunately, long-term exposure to immunosuppressive medications and their cumulative adverse effects, including renal dysfunction, metabolic syndrome, and malignancy, contribute to morbidity and mortality in the long-term transplant recipients leading to late graft loss. Therefore, judicious use of immunosuppressive medications, with utmost attention to their unique adverse event profiles, pharmacokinetics, and pharmacodynamics are essential in designing individualized regimens best suited for each transplant recipient. In this article, major classes of immunosuppressive medications used for induction and maintenance therapy in liver transplantation are reviewed, including their pharmacology, pharmacokinetics, drug interactions and common adverse drug reactions. The evidence for their preferential use is presented where available.