Prophylaxis of organ rejection in kidney or heart transplant patients

Everolimus is a macrolide immunosuppressant and an m-TOR inhibitor which has antiproliferative and antiangiogenic properties. It reduces protein synthesis and cell proliferation by binding to the FK binding protein-12 (FKBP-12), an intracellular protein, to form a complex that inhibits activation of mTOR (mammalian target of rapamycin) serine-threonine kinase activity. Also reduces angiogenesis by inhibiting vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1) expression

Bioavailability: ∼30%; Time to peak: 1 to 2 hours after oral administration; Plasma protein binding: 74%; Metabolism: extensively metabolized via CYP3A4; Elimination half-life: ∼30 hrs.

Hypersensitivity to everolimus, sirolimus, other rapamycin derivatives, or any component of the formulation.

D

Excretion in breast milk unknown/not recommended

Stomatitis, mouth ulcers, mucositis, diarrhea; rash, acneiform dermatitis; peripheral edema, hypertension; infections; asthenia, fatigue; cough, non-infection pneumonitis; ALT/AST level raised; anemia, decreased lymphocyte count, decreased platelet count; hypercholesterolemia, hypertriglyceridemia; and increased serum creatinine.

Renal transplant rejection; Prophylaxis: Oral: Initial: 0.75 mg twice daily; adjust maintenance dose if needed at a 4- to 5-day interval (from prior dose adjustment) based on serum concentrations (target, 3 to 8 ng/mL), tolerability, and response.
Heart transplantation, rejection prophylaxis: Oral: Initial: 0.75-1.5 mg twice daily in combination with cyclosporine and prednisone; adjust everolimus dose based on trough concentrations.