HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use AFINITOR safely and effectively. See full prescribing information for AFINITOR.
AFINITOR (everolimus) tablets for oral administration
Initial U.S. Approval: 2009
RECENT MAJOR CHANGES
Indications and Usage, Advanced Pancreatic Neuroendocrine
Tumors (1.1), Warnings and Precautions: Non-infectious
Pneumonitis (5.1), Infections (5.2), Oral Ulceration (5.3), Renal Failure Events (5.4),
Laboratory Tests and Monitoring (5.5)       05/2011
Indications and Usage, Subependymal Giant Cell Astrocytoma (1.3)       10/2010
Dosage and Administration (2)       10/2010
Warnings and Precautions: Non-infectious Pneumonitis (5.1),
Infections (5.2), Oral Ulceration (5.3), Drug-drug Interactions (5.6),
Hepatic Impairment (5.7), Vaccinations (5.8), Use in Pregnancy (5.9)       10/2010
INDICATIONS AND USAGE
AFINITOR is a kinase inhibitor indicated for the treatment of patients with:
progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic. The safety and effectiveness of AFINITOR in the treatment of patients with carcinoid tumors have not been established. (1.1)
advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. (1.2)
subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of AFINITOR is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been demonstrated. (1.3)
DOSAGE AND ADMINISTRATION
Advanced PNET or advanced RCC:
10 mg once daily with or without food. (2.1)
For patients with Child-Pugh class B hepatic impairment, reduce the AFINITOR dose to 5 mg once daily. (2.2)
If moderate inhibitors of CYP3A4 and/or P-glycoprotein (PgP) are required, reduce the AFINITOR dose to 2.5 mg once daily; if tolerated, consider increasing to 5 mg once daily. (2.2)
If strong inducers of CYP3A4 are required, increase AFINITOR dose in 5 mg increments to a maximum of 20 mg once daily. (2.2)
SEGA:
Initial dose based on body surface area with subsequent titration to attain trough concentrations of 5-10 ng/mL. (2.3)
If moderate inhibitors of CYP3A4 and/or PgP are required, reduce the AFINITOR dose by approximately 50%. Subsequent dosing should be based on therapeutic drug monitoring (TDM). (2.4)
If strong inducers of CYP3A4 are required, double the AFINITOR dose. Subsequent dosing should be based on TDM. (2.4)
Dose reduction and/or treatment interruption may be needed to manage adverse drug reactions. (2.2, 2.4)
DOSAGE FORMS AND STRENGTHS
2.5 mg, 5 mg, 7.5 mg and 10 mg tablets with no score (3)
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)
Oral ulceration: Mouth ulcers, stomatitis, and oral mucositis are common. Management includes mouthwashes (without alcohol or peroxide) and topical treatments. (5.3)
Renal failure events: Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR (5.4)
Laboratory test alterations: Elevations of serum creatinine, 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. (5.5)
Vaccinations: Avoid live vaccines and close contact with those who have received live vaccines. (5.8)
Use in pregnancy: Fetal harm can occur when administered to a pregnant woman. Apprise women of potential harm to the fetus. (5.9, 8.1)
ADVERSE REACTIONS
Advanced PNET: Most common adverse reactions (incidence ≥30%) are stomatitis, rash, diarrhea, fatigue, edema, abdominal pain, nausea, fever, and headache. (6.1)
Advanced RCC: Most common adverse reactions (incidence ≥30%) are stomatitis, infections, asthenia, fatigue, cough, and diarrhea. (6.2)
SEGA: Most common adverse reactions (incidence ≥30%) are stomatitis, upper respiratory tract infection, sinusitis, otitis media, and pyrexia. (6.3)
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 inhibitors: Avoid concomitant use. (2.2, 2.4, 5.6, 7.1)
Moderate CYP3A4 and/or PgP inhibitors: If combination is required, use caution and reduce dose of AFINITOR. (2.2, 2.4, 5.6, 7.1)
Strong CYP3A4 inducers: Avoid concomitant use. If combination cannot be avoided, increase dose of AFINITOR. (2.2, 2.4, 5.6, 7.2)
USE IN SPECIFIC POPULATIONS
Nursing mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. (8.3)

Hepatic impairment: AFINITOR should not be used in patients with Child-Pugh class C hepatic impairment. For advanced PNET and advanced RCC patients with Child-Pugh class B hepatic impairment, reduce AFINITOR dose. For SEGA patients with Child-Pugh class B hepatic impairment, adjustment to the starting dose may not be needed; however, subsequent dosing should be based on TDM. (2.2, 2.5, 5.7, 8.7)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 
Revised: 07/2011
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FULL PRESCRIBING INFORMATION: CONTENTS*
* Sections or subsections omitted from the full prescribing information are not listed 
1 INDICATIONS AND USAGE
1.1 Advanced Neuroendocrine Tumors of Pancreatic Origin (PNET) 
1.2 Advanced Renal Cell Carcinoma (RCC) 
1.3 Subependymal Giant Cell Astrocytoma (SEGA)
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose in Advanced Pancreatic Neuroendocrine Tumors and Advanced Renal Cell Carcinoma 
2.2 Dose Modifications in Advanced Pancreatic Neuroendocrine Tumors and Advanced Renal Cell Carcinoma
2.3 Recommended Dose in Subependymal Giant Cell Astrocytoma
2.4 Dose Modifications in Subependymal Giant Cell Astrocytoma
2.5 Therapeutic Drug Monitoring in Subependymal Giant Cell Astrocytoma
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Non-infectious Pneumonitis
5.2 Infections
5.3 Oral Ulceration
5.4 Renal Failure Events
5.5 Laboratory Tests and Monitoring
5.6 Drug-drug Interactions
5.7 Hepatic Impairment
5.8 Vaccinations
5.9 Use in Pregnancy
6 ADVERSE REACTIONS
6.1 Clinical Study Experience in Advanced Pancreatic Neuroendocrine Tumors
6.2 Clinical Study Experience in Advanced Renal Cell Carcinoma 
6.3 Clinical Study Experience in Subependymal Giant Cell Astrocytoma
7 DRUG INTERACTIONS
7.1 Agents that may Increase Everolimus Blood Concentrations
7.2 Agents that may Decrease Everolimus Blood Concentrations
7.3 Agents whose Plasma Concentrations may be Altered by Everolimus
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Advanced Neuroendocrine Tumors
14.2 Advanced Renal Cell Carcinoma 
14.3 Subependymal Giant Cell Astrocytoma
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION 
17.1 Non-infectious Pneumonitis
17.2 Infections
17.3 Oral Ulceration
17.4 Renal Failure Events
17.5 Laboratory Tests and Monitoring
17.6 Drug-drug Interactions
17.7 Hepatic Impairment
17.8 Vaccinations
17.9 Pregnancy
17.10 Dosing Instructions
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FULL PRESCRIBING INFORMATION