EVEROLIMUS THERAPEUTIC DRUG MONITORING IN A CANCER RENAL CANCER PATIENT
WHEN DOUBLE DRUG-DRUG INTERACTION IS DETECTED AND A REVIEW OF THE
LITERATURE
Abstract
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR)
widely used as an immunosuppressant in transplant patients. In
transplantation setting, several recommendations for therapeutic drug
monitoring are available, due to potential drug-drug interactions with
chronic medication, which can affect everolimus pharmacokinetic profile.
Everolimus is also used in breast, neuroendocrine and renal cancer, at
higher doses than in transplantation and without systematic drug
monitoring requirement. We present a case-report of a 72years-old woman
with epilepsy history to whom everolimus 10mg/daily was prescribed as
third line of treatment for renal cell carcinoma. The patient´s chronic
medication was checked by the outpatient hospital pharmacist before
initiating treatment. As a result, two major interactions with inducers
of CYP3A4 metabolism as carbamazepine and phenytoin were detected. Since
trough plasma concentration of everolimus could be affected, by these
pharmacokinetic interactions,a therapeutic drug monitoring of everolimus
was proposed. Based on the literature, Cmin plasma concentration
(Cminss) of everolimus over 10ng/ml is associated with better response
to treatment and progression free survival. During the oncologist
follow-up visit and according to pharmaceutical recommendations,
everolimus dosage was increased to 10mg every 12 hours. In the following
determinations of trough plasma everolimus concentration, Cmin grow up
from 3.7ng/ml to 10.8ng/mL. Depending on the CYP3A4 induction capacity
and potency of the drug/s administered concomitant to everolimus and how
many of them can potentially interact with it, therapeutic everolimus
monitoring would be advisable in order to adjust dosage if required to
prevent underexposure.