Efficacy and safety of everolimus in liver transplant recipients

Everolimus, is a new immunosuppressor that was approved in 2013 by the Food and Drug Administration (FDA) for its use in liver transplant. It was developed after sirolimus in order to overcome its poor bioavailability. The two immunosuppressors are structurally similar with the exception of the addition of an extra hydroxyethyl group at position 40 in everolimus which confers better pharmacokinetic characteristics. The toxicity profile of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, is different than calcineurinic inhibitors, commonly used for preventing graft rejection, and it is not associated with kidney dysfunction. In addition, it shows a better cardiovascular risk profile and could possibly prevent and treat some forms of cancer. Everolimus has demonstrated through randomized controlled studies to be at least as effective as the current standard of care for the prevention of graft rejection in solid organ transplants, preserving short and long-term graft dysfunction in selected patients. Everolimus has shown a relatively good safety profile, although there are some already known adverse effects, such as hyperlipidemia, edema, anemia, skin rash etc. Most of the adverse events that have been reported in liver transplant are present for a short time after the introduction of the drug and are manageable. Due to the narrow therapeutical margins it is necessary to monitor the everolimus drug level and also to take drug-drug interactions into consideration. After a careful study of its pros and cons, everolimus will become an important agent in liver transplant recipients for both de novo or in maintenance liver transplanted patients. Keywords: everolimus; mTOR inhibitors; renal function; tacrolimus liver transplant; cyclosporine; renal impairment. Received: February 4, 2014; Accepted: June 11, 2014; Published : November 13, 2014 Corresponding Author: Teresa Casanovas, MD, Liver Transplant Unit-Hepatitis Program, Hospital Universitari de Bellvitge, C/Feixa Llarga s/n Hospitalet de Llobregat, 08907 Barcelona, Spain E-mail : teresacasanovas@bellvitgehospital.cat .