Important Safety Information

There have been reports of noninfectious pneumonitis (including some with pulmonary hypertension as a secondary event), infections, and renal failure (including acute renal failure) in patients...

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

Indication

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

Important Safety Information

AFINITOR is contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives.

Noninfectious Pneumonitis

  • Noninfectious pneumonitis was reported in up to 19% of patients treated with AFINITOR; some cases were reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event. The incidence of grade 3 and 4 noninfectious pneumonitis was up to 4% and up to 0.2%, respectively. Fatal outcomes have been observed
  • Monitor for clinical symptoms or radiological changes. Consider opportunistic infections such as Pneumocystis jiroveci pneumonia (PJP) in the differential diagnosis. Withhold or permanently discontinue based on severity. Corticosteroids may be indicated until clinical symptoms resolve
  • For grade 2 to 4 noninfectious pneumonitis, withhold or permanently discontinue based on severity. Corticosteroids may be indicated until clinical symptoms resolve. Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required. 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, sepsis, septic shock, or resulting in multisystem organ failure) or fatal. The incidence of grade 3 and 4 infections was up to 10% and up to 3%, respectively
  • Complete treatment of preexisting invasive fungal infections prior to starting treatment. Monitor for signs and symptoms of infection. Withhold or permanently discontinue AFINITOR based on severity of infection. Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required

Severe Hypersensitivity Reactions

  • Hypersensitivity reactions to AFINITOR have been observed and include anaphylaxis, dyspnea, flushing, chest pain, and angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment)
  • The incidence of grade 3 hypersensitivity reactions was up to 1%. Permanently discontinue AFINITOR for the development of clinically significant hypersensitivity

Angioedema With Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors

  • Patients taking concomitant ACE inhibitors with AFINITOR may be at increased risk for angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment)
  • In a pooled analysis of randomized double-blind oncology clinical trials, the incidence of angioedema in patients taking AFINITOR with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor. Permanently discontinue AFINITOR for angioedema

Stomatitis

  • Stomatitis, including mouth ulcers and oral mucositis, has 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. Stomatitis most often occurs within the first 8 weeks of treatment
  • When starting AFINITOR, initiating dexamethasone alcohol-free oral solution as a swish –and- spit mouthwash reduces the incidence and severity of stomatitis. If stomatitis does occur, mouthwashes and/or other topical treatments are recommended, but alcohol-, hydrogen peroxide-, iodine-, or thyme-containing products 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 occurred in patients taking AFINITOR. Elevations of serum creatinine and proteinuria have been reported in patients taking AFINITOR. The incidence of grade 3 and 4 elevations of serum creatinine was up to 2% and up to 1%, respectively. The incidence of grade 3 and 4 proteinuria was up to 1% and up to 0.5%, respectively
  • Monitor renal function prior to starting AFINITOR and annually thereafter. Monitor renal function at least every 6 months in patients who have additional risk factors for renal failure

Impaired Wound Healing

  • AFINITOR 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

Metabolic Disorders

  • Hyperglycemia, hypercholesterolemia, and hypertriglyceridemia have been reported in patients taking AFINITOR at an incidence up to 75%, 86%, and 73%, respectively. The incidence of these grade 3 and 4 laboratory abnormalities was up to 15% and up to 0.4%, respectively
  • In nondiabetic patients, monitor fasting serum glucose prior to starting AFINITOR and annually thereafter
  • In diabetic patients, monitor fasting serum glucose more frequently as clinically indicated
  • Monitor lipid profile prior to starting AFINITOR and annually thereafter. When possible, achieve optimal glucose and lipid control prior to starting AFINITOR. For grade 3 to 4 metabolic events, withhold or permanently discontinue AFINITOR/AFINITOR DISPERZ based on severity

Myelosuppression

  • Anemia, lymphopenia, neutropenia, and thrombocytopenia have been reported in patients taking AFINITOR. The incidence of these grade 3 and 4 laboratory abnormalities was up to 16% and up to 2%, respectively
  • Monitor complete blood count prior to starting AFINITOR/AFINITOR DISPERZ every 6 months for the first year of treatment and annually thereafter. Withhold or permanently discontinue AFINITOR based on severity

Risk of Infection or Reduced Immune Response With Vaccinations

  • The safety of immunization with live vaccines during AFINITOR therapy has not been studied. Due to the potential increased risk of infection, avoid the use of live vaccines and close contact with individuals who have received live vaccines during treatment with AFINITOR

Embryo-Fetal Toxicity

  • Fetal harm can occur if AFINITOR is administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to avoid becoming pregnant and to use effective contraception while using AFINITOR and for 8 weeks after the last dose

Adverse Reactions

  • 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 (6%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), asthenia (2%), and diarrhea (2%)

Laboratory Abnormalities

  • 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 (6%), hypokalemia (4%), increased AST (4%), increased ALT (4%), and thrombocytopenia (3%)

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