Tacrolimustoxicity in organ transplantation: an overview

Tacrolimus is a macrolide lactone antibiotic, and acts as a calcineurin inhibitor. It is widely
used to prevent organ transplant rejection. It has been approved as first-line treatment after
organ transplantation. Tacrolimus has narrow therapeutic range and wide individual
variability in its pharmacokinetics. In organ transplantation, immunosuppression is associated
with important risks, in particular, related to infections and cardiovascular diseases, which are
the predominant causes of death in those with a functioning graft. This review focuses on
toxicity of tacrolimus after transplantation. Tacrolimus toxicity is a major determinant of
morbidity and mortality in organ recipients after transplantation. Therefore, reducing
toxicities has become a priority. To decrease the incidence of side effects, and expand graft
survival, the appropriate initial and maintenance dose of tacrolimus is essential. Clinical
conditions that influence tacrolimus pharmacokinetics, such as hemorrhage, systemic
inflammation and shock, all result in higher variations of tacrolimus concentrations. In
addition, unbound plasma concentration is a major important reasonable parameter for
monitoring of receiving optimal tacrolimus dosing in the unstable patient. Therefore, the
approach of tacrolimus monitoring is vital and will support to avoid tacrolimus toxicity in the
early days after transplantation