Important Safety Information

Advanced RCC Advanced PNET Advanced HR+ BC

Inhibition of mTOR by AFINITOR (everolimus) has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or vivo studies

Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC)

AFINITOR is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in
combination with exemestane after failure of treatment with letrozole or anastrozole.

Advanced Neuroendocrine Tumors of Pancreatic Origin (advanced PNET)

AFINITOR is indicated for the treatment of adults with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced, or metastatic disease. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors.

Advanced Renal Cell Carcinoma (RCC)

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

OUR COMMITMENT

  • Novartis Oncology is invested in further understanding the mTOR pathway, an important driver of progression in advanced forms of RCC, PNET, and HR+ BC
    • Important therapeutic approaches are fueled by an increased understanding of the pathways driving these diseases
  • The information on this website, based on both in vivo and in vitro study results, is part of the continued commitment Novartis has to conducting research into, and educating healthcare professionals about, mammalian target of rapamycin (mTOR)

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. Monitor for clinical symptoms or radiological changes. Opportunistic infections such as pneumocystis jiroveci pneumonia (PJP) should be considered in the differential diagnosis. Manage noninfectious pneumonitis by dose reduction or discontinuation until symptoms resolve, and consider the use of corticosteroids. For patients who require use of corticosteroids, prophylaxis for PJP may be considered. 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, candidiasis, or PJP; and viral infections, including reactivation of hepatitis B virus, have occurred. Some of these infections have been severe (eg, leading to sepsis, respiratory failure, 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 with AFINITOR. 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.

PJP has been reported in patients who received everolimus, sometimes with a fatal outcome. This may be associated with concomitant use of corticosteroids or other immunosuppressive agents; consider prophylaxis for PJP when concomitant use of these agents is required.

Oral Ulceration: Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44% to 78% 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-, hydrogen 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.

Impaired Wound Healing: Everolimus delays wound healing and increases the occurrence of wound-related complications like wound dehiscence, wound infection, incisional hernia, lymphocele, and seroma. These wound-related complications may require surgical intervention. Exercise caution with the use of AFINITOR in the perisurgical period.

Geriatric Patients: In the randomized advanced hormone receptor-positive, HER2-negative breast cancer study, the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥65 years of age compared with 2% in patients <65 years of age. Adverse reactions leading to permanent discontinuation occurred in 33% of patients ≥65 years of age compared with 17% in patients <65 years of age. Careful monitoring and appropriate dose adjustments for adverse reactions are recommended.

Laboratory Tests and Monitoring: Elevations of serum creatinine and proteinuria have been reported. Renal function (including measurement of blood urea nitrogen, urinary protein, or serum creatinine) should be evaluated prior to treatment and periodically thereafter, particularly in patients who have additional risk factors that may further impair renal function.

Hyperglycemia, hyperlipidemia, and hypertriglyceridemia have been reported. Blood glucose and lipids should be evaluated prior to treatment and periodically thereafter. More frequent monitoring is recommended when AFINITOR is coadministered with other drugs that may induce hyperglycemia. Management with appropriate medical therapy is recommended. When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR.

Reductions in hemoglobin, lymphocytes, neutrophils, and platelets have been reported. Monitoring of complete blood count is recommended prior to treatment and periodically thereafter.

Drug-Drug Interactions: Avoid coadministration with strong CYP3A4/PgP 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/PgP inhibitor is required (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). Avoid coadministration with strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if coadministration is required, consider doubling the daily dose of AFINITOR using increments of 5 mg or less.

Hepatic Impairment: Exposure to 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. Advise female patients of reproductive potential to use highly effective contraception while using AFINITOR and for up to 8 weeks after ending treatment.

Adverse Reactions (advanced HR+ BC): The most common adverse reactions (incidence ≥30%) were stomatitis (67%), infections (50%), rash (39%), fatigue (36%), diarrhea (33%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥2%) were stomatitis (8%), infections (5%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), and diarrhea (2%).

Laboratory Abnormalities (advanced HR+ BC): The most common laboratory abnormalities (incidence ≥50%) were hypercholesterolemia (70%), hyperglycemia (69%), increased aspartate transaminase (AST, 69%), anemia (68%), leukopenia (58%), thrombocytopenia (54%), lymphopenia (54%), increased alanine transaminase (ALT, 51%), and hypertriglyceridemia (50%). The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia (12%), hyperglycemia (9%), anemia (7%), decreased potassium (4%), increased AST (4%), increased ALT (4%), and thrombocytopenia (3%).

Adverse Reactions (advanced PNET): The most common adverse reactions (incidence ≥30%) were stomatitis (70%), rash (59%), diarrhea (50%), fatigue (45%), edema (39%), abdominal pain (36%), nausea (32%), fever (31%), headache (30%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were stomatitis (7%) and diarrhea (5.5%). Deaths primarily due to adverse events during the double-blind treatment phase occurred in 7 patients taking AFINITOR.

Laboratory Abnormalities (advanced PNET): The most common laboratory abnormalities (incidence ≥50%, all grades) were: decreased hemoglobin (86%) and bicarbonate (56%); increased fasting glucose (75%), alkaline phosphatase (74%), cholesterol (66%), and aspartate transaminase AST (56%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were: decreased hemoglobin (15%), lymphocytes (16%), and phosphate (10%), and increased glucose (17%) and alkaline phosphatase (8%).

Adverse Reactions (aRCC): 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%).

Laboratory Abnormalities (aRCC): 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%).

Please click here to see full Prescribing Information for AFINITOR.