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.