INTRODUCTION
Everolimus is an orally administered rapamycin derivate inhibiting the mammalian target of rapamycin (mTOR). This is a key signalling molecule in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway which is involved in the regulation, growth, proliferation, metabolism, survival and angiogenesis of cells that is often dysregulated in cancer (Figure I). Nowadays is used as cancer treatment at a fixed dose of 10mg/daily for metastatic renal cell cancer and in neuroendocrine tumours, and in combination with exemestane for advanced hormone receptor positive (HR+), negative human epidermal growth factor-2 (HER2-) breast cancer.1-3.
Everolimus is also used in transplant patients as immunosuppressant. Due to its narrow therapeutic index and pharmacokinetic inter-individual variability, routine therapeutic drug monitoring (TDM) is recommended to maintain a Cminss between 3-8 ng/ml4-5.. In cancer patients, Cminss below 10ng/ml have been associated with worse response to treatment while Cminss higher than 26.3ng/ml has been related to higher incidence of adverse events. However, in cancer setting, TDM is not currently performed. Variability in everolimus blood exposure may be influenced by several factors, including age, sex, body composition, genetic factors and drug-drug interactions which could affect its hepatic metabolism by cytochrome CYP3A47-9. We present a case report of a 72 years-old woman treated with everolimus for renal cell cancer and a double drug-drug interaction with carbamazepine and phenytoin.