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 reinitiated 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 taking 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 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.
Hepatic Impairment: Exposure of everolimus was increased in patients with hepatic impairment. For patients with SEGA and mild or moderate hepatic impairment, adjust the dose of AFINITOR or AFINITOR DISPERZ based on therapeutic drug monitoring. For patients with SEGA and severe hepatic impairment, reduce the starting dose of AFINITOR or AFINITOR DISPERZ by approximately 50% and adjust subsequent doses 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. For pediatric patients with SEGA who do not require immediate treatment with AFINITOR, complete the recommended childhood series of live virus vaccinations prior to the start of AFINITOR therapy. An accelerated vaccination schedule may be appropriate.
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%, all grades) in the phase 3 study were stomatitis (62%) and respiratory tract infection (31%). The most common grade 3/4 adverse reactions (incidence ≥2%) in the phase 3 study were stomatitis, pyrexia, pneumonia, gastroenteritis, aggression, agitation, and amenorrhea. Longer-term follow-up of 34.2 months (range 4.7 to 47.1 months) from the phase 2 study resulted in the following additional notable adverse reaction: cellulitis (29%).
Laboratory Abnormalities: The most common key laboratory abnormalities (incidence ≥50%, all grades) in the phase 3 study were hypercholesterolemia (81%) and elevated partial thromboplastin time (72%). The most common grade 3/4 laboratory abnormality (incidence ≥3%) in the phase 3 study was neutropenia (9%). Longer-term follow-up of 34.2 months (range 4.7 to 47.1 months) from the phase 2 study resulted in the following additional notable key laboratory abnormalities: hyperglycemia (25%) and elevated creatinine (14%).
Please see full Prescribing Information.
AFINITOR and AFINITOR DISPERZ are indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.
The effectiveness is based on demonstration of durable objective response, as evidenced by reduction in SEGA tumor volume. Improvement in disease-related symptoms and overall survival in patients with SEGA and TSC has not been demonstrated.