Everolimus

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Everolimus Tablets 2.5 mg tablet 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. 5 mg tablet White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘5’ on the other side. 7.5 mg tablet White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘7.5’ on the other side. 10 mg tablet White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘NAT’ on the other side.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Everolimus tablets are contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives [see Warnings and Precautions (5.3 )] .

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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 )].

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

11 DESCRIPTION

DESCRIPTION SECTION

Everolimus tablets are kinase inhibitors. The chemical name of everolimus is (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-{(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-aza-tricyclo[30.3.1.0 4,9 ]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone. The molecular formula is C 53 H 83 NO 14 and the molecular weight is 958.2 g/mol. The structural formula is: Everolimus tablets are supplied for oral administration and contain 2.5 mg, 5 mg, 7.5 mg and 10 mg of everolimus. The tablets also contain anhydrous lactose, butylated hydroxytoluene, crospovidone, hypromellose, and magnesium stearate as inactive ingredients.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

15 REFERENCES

REFERENCES SECTION

1. OSHA Hazardous Drugs. OSHA. http://www.osha.gov/SLTC/hazardous drugs/index.html.

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Everolimus Tablets 2.5 mg tablets 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; available in: Blisters of 28 tablets.........................NDC 63850-0058-2 (63850-0058-1) Each carton contains 4 blister cards of 7 tablets each Bottles of 30 tablets......................... NDC 63850-0058-4 5 mg tablets White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘5’ on the other side; available in: Blisters of 28 tablets.........................NDC 63850-0059-2 (63850-0059-1) Each carton contains 4 blister cards of 7 tablets each Bottles of 30 tablets......................... NDC 63850-0059-4 7.5 mg tablets White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘7.5’ on the other side; available in: Blisters of 28 tablets.........................NDC 63850-0060-2 (63850-0060-1) Each carton contains 4 blister cards of 7 tablets each Bottles of 30 tablets......................... NDC 63850-0060-4 10 mg tablets White to off-white coloured, oval, flat shaped tablets and no score, debossed with ‘EVR’ on one side and ‘NAT’ on the other side; available in: Blisters of 28 tablets………………NDC 63850-0061-2 (63850-0061-1) Each carton contains 4 blister cards of 7 tablets each Bottles of 30 tablets......................... NDC 63850-0061-4 Store Everolimus Tablets at 25°C (77°F); excursions permitted between 15°–30°C (59°–86°F). See USP Controlled Room Temperature. Store in the original container, protect from light and moisture. Follow special handling and disposal procedures for anticancer pharmaceuticals. 1

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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 ( 5.1 )] . 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 ( 5.2 )] . Hypersensitivity Reactions Advise patients of the risk of clinically significant hypersensitivity reactions and to promptly contact their healthcare provider or seek emergency care for signs of hypersensitivity reaction including rash, itching, hives, difficulty breathing or swallowing, flushing, chest pain, or dizziness [see Contraindications ( 4 ), Warnings and Precautions ( 5.3 )]. Angioedema with Concomitant Use of ACE Inhibitors Advise patients to avoid ACE inhibitors and to promptly contact their healthcare provider or seek emergency care for signs or symptoms of angioedema [see Warnings and Precautions ( 5.4 )] . Stomatitis Advise patients of the risk of stomatitis and to use alcohol-free mouthwashes during treatment [see Warnings and Precautions ( 5.5 )]. Renal Impairment Advise patients of the risk of developing kidney failure and the need to monitor their kidney function periodically during treatment [see Warnings and Precautions ( 5.6 )] . Risk of Impaired Wound Healing Advise patients that everolimus tablets may impair wound healing. Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions ( 5.7 )] . Geriatric Patients Inform patients that in a study conducted in patients with breast cancer, the incidence of deaths and adverse reactions leading to permanent discontinuation was higher in patients ≥ 65 years compared to patients < 65 years [see Warnings and Precautions (5.8) , Use in Specific Populations ( 8.5 )]. Metabolic Disorders Advise patients of the risk of metabolic disorders and the need to monitor glucose and lipids periodically during therapy [see Warnings and Precautions ( 5.9 )]. Myelosuppression Advise patients of the risk of myelosuppression and the need to monitor CBCs periodically during therapy [see Warnings and Precautions ( 5.10 )] . Risk of Infection or Reduced Immune Response with Vaccination Advise patients to avoid the use of live vaccines and close contact with those who have received live vaccines [see Warnings and Precautions ( 5.11 )]. Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 8 weeks after the last dose. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 weeks after the last dose [see Warnings and Precautions ( 5.12 ) and Use in Specific Populations ( 8.1, 8.3 )]. Lactation Advise women not to breastfeed during treatment with everolimus tablets and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )]. Infertility Advise males and females of reproductive potential of the potential risk for impaired fertility [see Use in Specific Populations ( 8.3 )]. Manufactured by: NATCO PHARMA LIMITED Kothur- 509 228 India. Distributed by: Breckenridge Pharmaceutical Inc. Boca Raton, FL 33487

Everolimus 2.5 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

28 Tablets Carton contains 4 individual blister cards of 7 tablets. Foil NDC-63850-0058-1 Carton NDC-63850-0058-2

Everolimus 5 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

28 Tablets Carton contains 4 individual blister cards of 7 tablets. Foil NDC-63850-0059-1 Carton NDC-63850-0059-2

Everolimus 7.5 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

28 Tablets Carton contains 4 individual blister cards of 7 tablets. Foil NDC-63850-0060-1 Carton NDC-63850-0060-2

Everolimus 10 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

28 Tablets Carton contains 4 individual blister cards of 7 tablets. Foil NDC-63850-0061-1 Carton NDC-63850-0061-2

Everolimus Tablets 2.5 mg bottle

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Everolimus tablets 2.5mg NDC 63850-0058-4 Bottle of 30’s

Everolimus Tablets 5 mg bottle

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Everolimus tablets 5mg NDC 63850-0059-4 Bottle of 30’s

Everolimus Tablets 7.5 mg bottle

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Everolimus tablets 7.5mg NDC 63850-0060-4 Bottle of 30’s

Everolimus Tablets 10 mg bottle

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Everolimus tablets 10mg NDC 63850-0061-4 Bottle of 30’s