Important Safety Information

AFINITOR^® is indicated for the treatment of patients with advanced renal cell carcinoma.

AFINITOR is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients. Non-infectious pneumonitis is a class effect of rapamycin derivatives, including AFINITOR. Fatal outcomes have been observed. If symptoms are moderate or severe, patients should be managed with dose interruption until symptoms improve or discontinuation, respectively. Corticosteroids may be indicated. AFINITOR may be reintroduced at 5 mg daily depending on the individual clinical circumstances.

AFINITOR has immunosuppressive properties and may predispose patients to infections. Localized and systemic infections (bacterial and invasive fungal infections) have occurred. Some of these infections have been severe or fatal. Complete treatment of pre-existing invasive fungal infections prior to starting treatment. If a diagnosis of invasive systemic fungal infection is made, discontinue AFINITOR and treat with appropriate antifungal therapy. Oral ulcerations have occurred in patients treated with AFINITOR. In such cases, topical treatments are recommended, but alcohol- or peroxide-containing mouthwashes should be avoided. Antifungal agents should not be used unless fungal infection has been diagnosed.

Elevations of serum creatinine, glucose, lipids and triglycerides and reductions of hemoglobin, lymphocytes, neutrophils and platelets have been reported in clinical trials. Renal function, hematological parameters, blood glucose and lipids should be evaluated prior to treatment and periodically thereafter. When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR.

Co-administration with strong or moderate inhibitors of CYP3A4 or PgP should be avoided. Increase in the AFINITOR dose is recommended when co-administered with a strong CYP3A4 inducer.

AFINITOR should not be used in patients with severe hepatic impairment. The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR.

Fetal harm can occur if AFINITOR is administered to a pregnant woman. The most common adverse reactions (incidence ≥30%) were stomatitis, infections, asthenia, fatigue, cough and diarrhea. The most common grade 3/4 adverse reactions (incidence ≥3%) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain and asthenia. The most common laboratory abnormalities (incidence ≥50%) were anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia and increased creatinine. The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia and hypercholesterolemia. Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the AFINITOR arm.