1.1 Non-Small Cell Lung Cancer (NSCLC)

TARCEVA is indicated for:

•

The first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test [see Clinical Studies (14.1)].

•

The maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy [see Clinical Studies (14.2)].

•

The treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen [see Clinical Studies (14.3)].

Limitations of use:

•

TARCEVA is not recommended for use in combination with platinum-based chemotherapy [see Clinical Studies (14.4)].

•

Safety and efficacy of TARCEVA have not been eva luated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution [see Clinical Studies (14.1)].

1.2 Pancreatic Cancer

TARCEVA in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer [see Clinical Studies (14.5)].

2.1 Patient Selection

Select patients for the first-line treatment of metastatic NSCLC with TARCEVA based on the presence of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in tumor specimens [See Clinical Studies (14.1)]. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

2.2 Recommended Dose – NSCLC

The recommended daily dose of TARCEVA for NSCLC is 150 mg taken on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs.

2.3 Recommended Dose – Pancreatic Cancer

The recommended daily dose of TARCEVA for pancreatic cancer is 100 mg taken once daily in combination with gemcitabine. Take TARCEVA on an empty stomach, i.e., at least one hour before or two hours after the ingestion of food. Treatment should continue until disease progression or unacceptable toxicity occurs [see Clinical Studies (14.5)].

2.4 Dose Modifications

Discontinue TARCEVA for:

•

Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.1)].

•

Severe hepatic toxicity that does not improve significantly or resolve within three weeks [see Warnings and Precautions (5.3)].

•

Gastrointestinal perforation [see Warnings and Precautions (5.4)].

•

Severe bullous, blistering or exfoliating skin conditions [see Warnings and Precautions (5.5)].

•

Corneal perforation or severe ulceration [see Warnings and Precautions (5.9)].

Withhold TARCEVA:

•

During diagnostic eva luation for possible ILD.

•

For severe (CTCAE grade 3 to 4) renal toxicity, and consider discontinuation of TARCEVA [see Warnings and Precautions (5.2)].

•

In patients without pre-existing hepatic impairment for total bilirubin levels greater than 3 times the upper limit of normal or transaminases greater than 5 times the upper limit of normal, and consider discontinuation of TARCEVA [see Warnings and Precautions (5.3)].

•

In patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases values over baseline and consider discontinuation of TARCEVA [see Warnings and Precautions (5.3)].

•

For persistent severe diarrhea not responsive to medical management (e.g., loperamide).

•

For severe rash not responsive to medical management.

•

For keratitis of (NCI-CTC version 4.0) grade 3-4 or for grade 2 lasting more than 2 weeks [see Warnings and Precautions (5.9)].

•

For acute/worsening ocular disorders such as eye pain, and consider discontinuation of TARCEVA [see Warnings and Precautions (5.9)].

Reduce TARCEVA by 50 mg decrements:

•

If severe reactions occur with concomitant use of strong CYP3A4 inhibitors [such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., ciprofloxacin). Avoid concomitant use if possible [see Drug Interactions (7)].

•

When restarting therapy following withholding treatment for a dose-limiting toxicity that has resolved to baseline or grade ≤ 1.

Increase TARCEVA by 50 mg increments as tolerated for:

•

Concomitant use with CYP3A4 inducers, such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John’s Wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use, if possible [see Drug Interactions (7)].

•

Concurrent cigarette smoking. Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of TARCEVA to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Drugs Affecting Gastric pH

•

Avoid concomitant use of TARCEVA with proton pump inhibitors if possible. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period.

•

If treatment with an H 2-receptor antagonist such as ranitidine is required, TARCEVA must be taken 10 hours after the H 2-receptor antagonist dosing and at least 2 hours before the next dose of the H 2-receptor antagonist.

•

Although the effect of antacids on erlotinib pharmacokinetics has not been eva luated, the antacid dose and the TARCEVA dose should be separated by several hours, if an antacid is necessary.  

5.1 Interstitial Lung Disease (ILD)

Cases of serious ILD, including fatal cases, can occur with TARCEVA treatment. The overall incidence of ILD in approximately 32,000 TARCEVA-treated patients in uncontrolled studies and studies with concurrent chemotherapy was approximately 1.1%. In patients with ILD, the onset of symptoms was between 5 days to more than 9 months (median 39 days) after initiating TARCEVA therapy.

Withhold TARCEVA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic eva luation. If ILD is confirmed, permanently discontinue TARCEVA [see Dosage and Administration (