ments of 5 mg or less. (2.2)
SEGA with TSC:
•4.5 mg/m2 once daily; adjust dose to attain trough concentrations of 5-15 ng/mL. (2.3)
•Assess trough concentrations approximately 2 weeks after initiation of treatment, a change in dose, a change in co-administration of CYP3A4 /PgP inducers or inhibitors, a change in hepatic function, or a change in dosage form between AFINITOR Tablets and AFINITOR DISPERZ. (2.3, 2.4)
•For patients with severe hepatic impairment reduce the starting dose of AFINITOR Tablets or AFINITOR DISPERZ. (2.3, 2.5)
•If concomitant use of moderate inhibitors of CYP3A4 /PgP is required, reduce the dose of AFINITOR Tablets or AFINITOR DISPERZ by 50%. (2.3, 2.5)
•If concomitant use of strong inducers of CYP3A4/PgP is required, double the dose of AFINITOR Tablets or AFINITOR DISPERZ. (2.3, 2.5)
DOSAGE FORMS AND STRENGTHS
AFINITOR Tablets: 2.5 mg, 5 mg, 7.5 mg, and 10 mg tablets with no score (3.1)
AFINITOR DISPERZ (everolimus tablets for oral suspension): 2 mg, 3 mg, and 5 mg tablets for oral suspension with no score (3.2)
CONTRAINDICATIONS
Hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients (4)
WARNINGS AND PRECAUTIONS
•Non-infectious pneumonitis: Monitor for clinical symptoms or radiological changes; fatal cases have occurred. Manage by dose reduction or discontinuation until symptoms resolve, and consider use of corticosteroids. (5.1)
•Infections: Increased risk of infections, some fatal. Monitor for signs and symptoms, and treat promptly. (5.2)
•Angioedema: Patients taking concomitant ACE inhibitor therapy may be at increased risk for angioedema. (5.3)
•Oral ulceration: Mouth ulcers, stomatitis, and oral mucositis are common. Management includes mouthwashes and topical treatments. (5.4)
•Renal failure: Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed. (5.5)
•Impaired wound healing: Increased risk of wound-related complications. Monitor signs and symptoms. Exercise caution in the peri-surgical period. (5.6)
•Laboratory test alterations: Elevations of serum creatinine, urinary protein, blood glucose, and lipids may occur. Decreases in hemoglobin, neutrophils, and platelets may also occur. Monitor renal function, blood glucose, lipids, and hematologic parameters prior to treatment and periodically thereafter. (5.8)
•Vaccinations: Avoid live vaccines and close contact with those who have received live vaccines. (5.11)
•Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman. Apprise women of potential harm to the fetus. (5.12, 8.1)
ADVERSE REACTIONS
Advanced HR+ BC, advanced PNET, advanced RCC: Most common adverse reactions (incidence ≥30%) include stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, fever, asthenia, cough, headache and decreased appetite. (6.1, 6.2, 6.3)
Renal angiomyolipoma with TSC: Most common adverse reaction (incidence ≥ 30%) is stomatitis. (6.4)
SEGA with TSC: Most common adverse reactions (incidence ≥ 30%) are stomatitis and respiratory tract infection. (6.5)
To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
•Strong CYP3A4/PgP inhibitor |
