AFINITOR is indicated for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection.

The effectiveness of AFINITOR is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been demonstrated.

Important Safety Information

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

Non-infectious Pneumonitis: Non-infectious pneumonitis is a class effect of rapamycin derivatives, including AFINITOR. Fatal outcomes have been observed. If symptoms are moderate, patients should be managed with dose interruption until symptoms improve. If symptoms are severe, AFINITOR therapy should be discontinued. Under both circumstances, corticosteroids may be indicated and AFINITOR may be re-initiated at a daily dose approximately 50% lower than the dose previously administered depending on the individual clinical circumstances.

Infections: AFINITOR has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections, including infections with opportunistic pathogens. Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections, and viral infections including reactivation of hepatitis B virus have occurred. Some of these infections have been severe (e.g., leading to respiratory or hepatic failure) or fatal. Treatment of pre-existing invasive fungal infections should be completed prior to starting treatment. While taking AFINITOR, be vigilant for signs and symptoms of infection; if a diagnosis of infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of AFINITOR. If a diagnosis of invasive systemic fungal infection is made, discontinue AFINITOR and treat with appropriate antifungal therapy.

Oral Ulceration: Oral ulcerations (i.e., mouth ulcers, stomatitis, and oral mucositis) have occurred in patients treated with AFINITOR. In the SEGA study, 86% of AFINITOR-treated patients developed stomatitis which was mostly CTCAE grade 1 or 2. 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.

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, 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 co-administration with strong CYP3A4 inhibitors. Use caution and reduce the AFINITOR dose if co-administration with a moderate CYP3A4 and/or PgP inhibitor is required. Avoid co-administration with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if co-administration is required, increase the AFINITOR dose.

Hepatic Impairment: AFINITOR should not be used in patients with severe hepatic impairment. Exposure of everolimus was increased in patients with moderate hepatic impairment. In these patients, adjustment to the starting dose may not be needed; however, subsequent dosing should be individualized based on therapeutic drug monitoring.

Vaccinations: The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR. The timing of routine vaccinations in pediatric patients with SEGA should be considered prior to the start of AFINITOR therapy.

Use in Pregnancy: Fetal harm can occur if AFINITOR is administered to a pregnant woman. Women of childbearing potential should be advised to use an 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%, all grades) were stomatitis (86%), upper respiratory tract infection (82%), sinusitis (39%), otitis media (36%), and pyrexia (32%). The most common grade 3 adverse reactions (incidence ≥3%) were convulsion (7%), sinusitis (4%), pneumonia (4%), viral bronchitis (4%), tooth infection (4%), stomatitis (4%), aspiration (4%), cyclic neutropenia (4%), sleep apnea syndrome (4%), vomiting (4%), dizziness (4%), white blood cell count decreased (4%), and neutrophil count decreased (4%). A grade 4 convulsion (4%) was reported.

Laboratory Abnormalities: The most common laboratory abnormalities (incidence ≥50%, all grades) were elevations in aspartate transaminase (AST) concentrations (89%), total cholesterol (68%), and reductions in white blood cell counts (54%). Grade 3 laboratory abnormalities were elevated AST concentrations (4%) and low absolute neutrophil count (4%).