Everolimus

1. INDICATIONS AND USAGE Everolimus tablets are a kinase inhibitor 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. ( 1.1 ) Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. Limitations of Use: Everolimus tablets are not indicated for the treatment of patients with functional carcinoid tumors. …

• DOSAGE AND ADMINISTRATION Do not combine everolimus tablets and everolimus tablets for oral suspension to achieve the total daily dose
• Modify the dose for patients with hepatic impairment or for patients taking drugs that inhibit or induce P-glycoprotein (P-gp) and CYP3A4
• Breast Cancer: 10 mg orally once daily
• NET: 10 mg orally once daily
• RCC: 10 mg orally once daily
• TSC-Associated Renal Angiomyolipoma: 10 mg orally once daily
• TSC-Associated SEGA: 4.5 mg/m 2 orally once daily; adjust dose to attain trough concentrations of 5-15 ng/mL
• TSC-Associated Partial-Onset Seizures: 5 mg/ m 2 orally once daily; adjust dose to attain trough concentrations of 5-­15 ng/mL
• Important Dosage Information Everolimus tablets and everolimus tablets for oral suspension are two different dosage forms
• Select the recommended dosage form based on the indication [see Indications and Usage ]
• Do not combine everolimus tablets and everolimus tablets for oral suspension to achieve the total dose
• Modify the dosage for patients with hepatic impairment or for patients taking drugs that inhibit or induce P-glycoprotein (P-gp) and CYP3A4 [see Dosage and Administration ]
• Recommended Dosage for Hormone Receptor-Positive, HER2-Negative Breast Cancer The recommended dosage of everolimus tablets is 10 mg orally once daily until disease progression or unacceptable toxicity. …

3. DOSAGE FORMS AND STRENGTHS Everolimus Tablets: 2.5 mg, 5 mg, 7.5 mg, and 10 mg tablets with no score ( 3 ) Everolimus tablets for oral suspension: 2 mg, 3 mg, and 5 mg tablets ( 3 ) Everolimus Tablets 2.5 mg: White to off-white coloured, oval, flat shaped tablets and no score, debossed with 'EVR' on one side and '2.5' on the other side. …

• TSC-Associated SEGA The safety and effectiveness of everolimus tablets/everolimus tablets for oral suspension have been established
• In pediatric patients age 1 year and older with TSC-associated SEGA that requires therapeutic intervention but cannot be curatively resected
• Use of everolimus tablets/everolimus tablets for oral suspension for this indication is supported by evidence from a randomized, double-blind, placebo-controlled trial in adult and pediatric patients (EXIST-1); an open-label, single-arm trial in adult and pediatric patients (Study 2485); and additional pharmacokinetic data i …

In BOLERO-2, 40% of patients with breast cancer treated with everolimus tablets were ≥ 65 years of age, while 15% were ≥ 75 years of age. No overall differences in effectiveness were observed between elderly and younger patients. The incidence of deaths due to any cause within 28 days of the last everolimus tablets dose was 6% in patients ≥ 65 years of age compared to 2% in patients < 65 years of age. …

• PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)
• Non-infectious Pneumonitis Advise patients of the risk of developing non-infectious pneumonitis and to immediately report any new or worsening respiratory symptoms to their healthcare provider [see Warnings and Precautions ]
• Infections Advise patients that they are more susceptible to infections and that they should immediately report any signs or symptoms of infections to their healthcare provider [see Warnings and Precautions ]. …

• CONTRAINDICATIONS Everolimus tablets/everolimus tablets for oral suspension are contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives [see Warnings and Precautions ]
• Clinically significant hypersensitivity to everolimus or to other rapamycin derivatives

7. DRUG INTERACTIONS P-gp and strong CYP3A4 inhibitors: Avoid concomitant use. ( 2.11 , 7.1 ) P-gp and moderate CYP3A4 inhibitors: Reduce the dose as recommended. ( 2.11 , 7.1 ) P-gp and strong CYP3A4 inducers: Increase the dose as recommended. ( 2.12 , 7.1 ) 7.1 Effect of Other Drugs on Everolimus Tablets/Everolimus Tablets for Oral Suspension Inhibitors Avoid the concomitant use of P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.11) , Clinical Pharmacology (12.3) ] . …

5. WARNINGS AND PRECAUTIONS Non-Infectious Pneumonitis: Monitor for clinical symptoms or radiological changes. Withhold or permanently discontinue based on severity. ( 2.9 , 5.1 ) Infections: Monitor for signs and symptoms of infection. Withhold or permanently discontinue based on severity. ( 2.9 , 5.2 ) Severe Hypersensitivity Reactions: Permanently discontinue for clinically significant hypersensitivity. ( 5.3 ) Angioedema: Patients taking concomitant angiotensin-converting-enzyme (ACE) inhibitors may be at increased risk for angioedema. Permanently discontinue for angioedema. ( 5.4 , 7.2 ) Stomatitis: Initiate dexamethasone alcohol-free mouthwash when starting treatment. …

6. ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Non-Infectious Pneumonitis [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Severe Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Angioedema with Concomitant Use of ACE inhibitors [see Warnings and Precautions (5.4) ] Stomatitis [see Warnings and Precautions (5.5) ] Renal Failure [see Warnings and Precautions (5.6) ] Impaired Wound Healing [see Warnings and Precautions (5.7) ] Metabolic Disorders [see Warnings and Precautions (5.9) ] Myelosuppression [see Warnings and Precautions (5.10) ] Radiation Sensitization and Radiation Recall [se …

8.1 Pregnancy Risk Summary Based on animal studies and the mechanism of action [see Clinical Pharmacology (12.1) ] , everolimus tablets/everolimus tablets for oral suspension can cause fetal harm when administered to a pregnant woman. There are limited case reports of everolimus tablets use in pregnant women; however, these reports are not sufficient to inform about risks of birth defects or miscarriage. …

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). See USP Controlled Room Temperature. Store in the original container, protect from light and moisture. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.