indication

Investigated for use/treatment in transplant (rejection) and renal cell carcinoma.

mechanism of action

Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake.

route of elimination

After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine.

drug interactions

Bicalutamide: CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of everolimus. Consider therapy modification. Recommendations regarding optimal management of this interaction vary according to specific indication and product used.

Clarithromycin: The macrolide, clarithromycin, may increase the serum concentration and toxicity of everolimus.

Clotrimazole: CYP3A4 Inhibitors (Moderate)such as clotrimazole may increase the serum concentration of everolimus. The prescribing information for the Afinitor branded everolimus product lists indication-specific recommendations for managing this interaction.

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Everolimus prescribing information recommends avoiding concurrent use with strong CYP3A4 inhbitors.

Erythromycin: The macrolide, erythromycin, may increase the serum concentration and toxicity of everolimus.

Fluconazole: Fluconazole may increase everolimus levels/toxicity.

Itraconazole: Itraconazole may increase everolimus levels/toxicity.

Ketoconazole: Ketoconazole may increase everolimus levels/toxicity.

Verapamil: Concomitant administration may increase the serum concentrations of both agents. Concurrent use should be avoided.

Voriconazole: Voriconzole, a strong CYP3A4 inhibitor, may increase the serum concentration of everolimus by decreasing its metabolism. Concurrent therapy should be avoided.