AFINITOR is indicated for the treatment of adults with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.

Important Safety Information

AFINITOR is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients.

Noninfectious Pneumonitis:

• Noninfectious pneumonitis was reported in up to 19% of patients treated with AFINITOR. The incidence of Common Terminology Criteria (CTC) grade 3 and 4 noninfectious pneumonitis was up to 4.0% and up to 0.2%, respectively. Fatal outcomes have been observed
• If symptoms are moderate, patients should be managed with dose interruption until symptoms improve
• The use of corticosteroids may be indicated. For grade 4 cases, discontinue AFINITOR. Corticosteroids may be indicated until symptoms resolve
• For grade 3 cases, interrupt AFINITOR until resolution to grade ≤1
• AFINITOR may be reintroduced at a daily dose approximately 50% lower than the dose previously administered, depending on the individual clinical circumstances. If toxicity recurs at grade 3, consider discontinuation of AFINITOR
• The development of pneumonitis has been reported even at a reduced dose

Infections:

• AFINITOR has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections (including those with opportunistic pathogens). Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections such as aspergillosis or candidiasis, and viral infections, including reactivation of hepatitis B virus, have occurred
• Some of these infections have been severe (eg, leading to respiratory or hepatic failure) or fatal
• Physicians and patients should be aware of the increased risk of infection with AFINITOR
• Treatment of preexisting invasive fungal infections should be completed prior to starting treatment
• Be vigilant for signs and symptoms of infection and institute appropriate treatment promptly; interruption or discontinuation of AFINITOR should be considered
• Discontinue AFINITOR if invasive systemic fungal infection is diagnosed and institute appropriate antifungal treatment

Oral Ulceration:

• Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44% to 86% across the clinical trial experience. Grade 3/4 stomatitis was reported in 4% to 9% of patients
• In such cases, topical treatments are recommended, but alcohol-, peroxide-, iodine-, or thyme-containing mouthwashes should be avoided
• Antifungal agents should not be used unless fungal infection has been diagnosed

Renal Failure:

• Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR

Laboratory Tests and Monitoring:

• Elevations of serum creatinine, proteinuria, glucose, lipids, and triglycerides, and reductions of hemoglobin, lymphocytes, neutrophils, and platelets, have been reported
• Renal function (including measurement of blood urea nitrogen, urinary protein, or serum creatinine), blood glucose, lipids, and hematologic parameters 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

Drug-Drug Interactions:

• Avoid coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole)
• Use caution and reduce the AFINITOR dose to 2.5 mg daily if coadministration with a moderate CYP3A4 and/or PgP inhibitor is required (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem)
• Avoid coadministration with strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if coadministration is required, increase the AFINITOR dose from 10 mg daily up to 20 mg daily, using 5-mg increments

Hepatic Impairment:

• Exposure of everolimus was increased in patients with hepatic impairment
• For patients with severe hepatic impairment (Child-Pugh class C), AFINITOR may be used at a reduced dose if the desired benefit outweighs the risk. For patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, a dose reduction is recommended

Vaccinations:

• The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR

Embryo-Fetal Toxicity:

• Fetal harm can occur if AFINITOR is administered to a pregnant woman. Women of childbearing potential should be advised to use a highly effective method of contraception while using AFINITOR and for up to 8 weeks after ending treatment

Adverse Reactions:

• The most common adverse reactions (incidence ≥30%) were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), cough (30%), and diarrhea (30%)
• The most common grade 3/4 adverse reactions (incidence ≥5%) were infections (10%), dyspnea (7%), stomatitis (5%), and fatigue (5%). Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the AFINITOR arm

Laboratory Abnormalities:

• The most common laboratory abnormalities (incidence ≥50%, all grades) were: decreased hemoglobin (92%) and lymphocytes (51%); and increased cholesterol (77%), triglycerides (73%), glucose (57%), and creatinine (50%)
• The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were decreased hemoglobin (13%), lymphocytes (18%), and phosphate (6%), and increased glucose (16%)

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