|Values are valid only on day of printing.|
Everolimus is an immunosuppressive agent derived from sirolimus (rapamycin). Both drugs function via inhibition of mTOR 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 CYP3A4, 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 FDA approval for prophylaxis of graft rejection in solid organ transplant, an application which 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.
Management of everolimus immunosuppression in solid organ transplant
Therapeutic targets vary by transplant site and institution protocol. Heart and kidney transplant guidelines suggest a therapeutic range of 3 to 8 ng/mL.
Measurement of drug concentrations in oncology chemotherapy is less common, thus no therapeutic range is established for this application.
Therapeutic targets vary by transplant site and institution protocol. Established ranges refer to trough (predose) concentrations.
1. Eisen HJ, Tuzcu EM, Dorent R, et al: Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003;349(9):847-858
2. Kovarik JM, Beyer D, Schmouder RL: Everolimus drug interactions: application of a classification system for clinical decision making. Biopharm Drug Dispos 2006;27(9):421-426
3. Rothenburger M, Zuckermann A, Bara C, et al: Recommendations for the use of everolimus (Certican) in heart transplantation: results from the second German-Austrian Certican Consensus Conference. J Heart Lung Transplant 2007;26(4):305-311
4. Sanchez-Fructuoso AI: Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials. Expert Opin Drug Metab Toxicol 2008;4(6):807-819