Clinical Information

Everolimus is an immunosuppressive agent derived from sirolimus (rapamycin). Both drugs function via inhibition of mTOR (mechanistic target of rapamycin) signaling and share similar pharmacokinetic and toxicity profiles. Everolimus has a shorter half-life than sirolimus, which allows for more rapid achievement of steady-state pharmacokinetics. Everolimus is extensively metabolized, primarily by cytochrome P450 (CYP) 3A4, thus its use with inducers or inhibitors of that enzyme may require dose adjustment. The most common adverse effects include hyperlipidemia, thrombocytopenia, and nephrotoxicity. Everolimus is useful as adjuvant therapy in renal cell carcinoma and other cancers. It recently gained US Food and Drug Administration approval for prophylaxis of graft rejection in solid organ transplant, an application that has been accepted for years in Europe. The utility of therapeutic drug monitoring has not been established for everolimus as an oncology chemotherapy agent; however, measuring blood drug concentrations is common practice for its use in transplant. Therapeutic targets vary depending on the transplant site and institution protocol. Guidelines for heart and kidney transplants suggest that trough (immediately prior to the next scheduled dose) blood concentrations between 3 and 8 ng/mL provide optimal outcomes.