RECENT MAJOR CHANGES

Warnings and Precautions, Hepatic Impairment (5.2) 09/2008

Warnings and Precautions, Hepatotoxicity (5.3) 09/2008

Warning and Precautions, Renal Failure (5.4) 09/2008

INDICATIONS AND USAGE

TARCEVA is a tyrosine kinase inhibitor indicated for the treatment of:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. (1.1)
• First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. (1.2)

DOSAGE AND ADMINISTRATION

• The dose for NSCLC is 150 mg/day. (2.1)
• The dose for pancreatic cancer is 100 mg/day. (2.2)
• All doses of TARCEVA should be taken at least one hour before or two hours after food.(2.1, 2.2)
• Reduce in 50 mg decrements, when necessary. (2.3)

DOSAGE FORMS AND STRENGTHS

• Tablets: 25 mg, 100 mg and 150 mg. (3)

CONTRAINDICATIONS

None. (4)

WARNINGS AND PRECAUTIONS

• Interstitial Lung Disease (ILD)-like events, including fatalities have been infrequently reported. Interrupt TARCEVA if acute onset of new or progressive unexplained pulmonary symptoms, such as dyspnea, cough and fever occur. Discontinue TARCEVA if ILD is diagnosed. (5.1)
• Monitor patients with hepatic impairment closely. Interrupt or discontinue TARCEVA if changes in liver function are severe (5.2)
• Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported. Monitor periodic liver function testing. Interrupt or discontinue TARCEVA if liver function changes are severe. (5.3)
• Cases of acute renal failure (including fatalities), and renal insufficiency have been reported.Interrupt TARCEVA in the event of dehydration. Monitor renal function and electrolytes in patients at risk of dehydration. (5.4)
• Myocardial infarction/ischemia has been reported, including fatalities, in patients with pancreatic cancer. (5.5)
• Cerebrovascular accidents, including a fatality, have been reported in patients with pancreatic cancer. (5.6)
• Microangiopathic Hemolytic Anemia with thrombocytopenia has been reported in patients with pancreatic cancer. (5.7)
• Women should be advised to avoid pregnancy while on TARCEVA. Treatment should only be continued if the potential benefit to the mother outweighs the risk to the fetus. (5.8)
• International Normalized Ratio (INR) elevations and bleeding events, some associated with concomitant warfarin administration have been reported. Monitor patients taking warfarin or other coumarin-derivative anticoagulants. (5.9)

ADVERSE REACTIONS

The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. (6.1)

The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia. (6.2)

DRUG INTERACTIONS

• CYP3A4 inhibitors may increase erlotinib plasma concentrations. (7)
• CYP3A4 inducers may decrease erlotinib plasma concentrations. (7)
• CYP1A2 inducers may decrease erlotinib plasma concentrations. (7)
• Erlotinib solubility is pH dependent. Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and hence its absorption. (7)
• Cigarette smoking decreases erlotinib plasma concentrations (7)