Approved March 30, 2009

EVEROLIMUS
(FDA Category 1S)

AFINITOR(R) (Novartis Pharmaceuticals Corporation) is an inhibitor of the kinase mTor which leads to reduced cell proliferation and angiogenesis.

DOSING INFORMATION: The recommended dose of everolimus is 10 milligrams orally once daily. Dose adjustments are required for patients who have Child-Pugh class B hepatic impairment, are receiving concomitant moderate or strong CYP3A4 inhibitors, or in those who experience severe and/or intolerable adverse effects.

PHARMACOKINETICS: Peak plasma levels of everolimus occur at 1 to 2 hours after oral administration and steady state is achieved within 2 weeks. Everolimus is approximately 74% bound to plasma proteins and is a substrate of CYP3A4 and p-glycoprotein. The mean elimination half-life is approximately 30 hours.

CAUTIONS: Contraindicated in patients with a known hypersensitivity to everolimus or other rapamycin derivatives. Use with caution in pregnant women as it may cause fetal harm. The most common adverse reactions include stomatitis, infections, asthenia, fatigue, cough, and diarrhea. Noninfectious pneumonitis and serious infections have occurred.

FDA APPROVED INDICATIONS: Everolimus is indicated for the treatment of advanced renal cell carcinoma after failure of sunitinib or sorafenib therapy.