Iressa (gefitinib) 250 mg Tablets - Advisories, Warnings and Recalls for Health Professionals

Health Canada Endorsed Important Safety Information on IRESSA (gefitinib) 250 mg Tablets

AstraZeneca Canada Inc.

1004 Middlegate Road

Mississauga Ontario

Canada L4Y 1M4

Tel: (905) 277-7111

Fax: (905) 275-6271

August 26, 2005

Subject: Health Canada recommends restricting the indication for IRESSA® to patients whose tumours are EGFR expression status positive or unknown

Dear Health Care Professional:

AstraZeneca Canada Inc., in consultation with Health Canada, would like to inform you of a restriction to the indication of IRESSA^® (gefitinib). IRESSA is an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), which received a Notice of Compliance with conditions (NOC/c) on December 17, 2003 for third line therapy of locally advanced or metastatic non-small cell lung cancer (NSCLC). The approval was based on the Objective Response Rate from two phase II studies.

In December 2004, Health Canada received information on interim results from a pivotal, phase III, survival commitment study (ISEL). The study was to compare the effect of IRESSA vs. placebo in advanced NSCLC patients, who were refractory or intolerant to their most recent regimen, following one or two prior chemotherapy regimens. Results in the overall population show that IRESSA did not improve survival while statistically significant objective responses (8.0% vs 1.3% p<0.0001) were achieved.< p>

An exploratory objective of the ISEL trial was to investigate the correlation of epidermal growth factor receptor (EGFR) with efficacy in patients where such tumour material was available. Analysis of the EGFR expression data suggests that patients with EGFR expression status positive or unknown tumours could benefit from IRESSA. However, patients with EGFR expression status negative tumours were unlikely to benefit from IRESSA treatment.

Changes to the IRESSA^® Product Monograph will include:

INDICATIONS and CLINICAL USE section:

IRESSA is indicated as monotherapy (third line therapy) after failure of prior platinum-based and docetaxel chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer whose tumours are EGFR expression status positive or unknown. The efficacy of IRESSA is based on objective responses. There are no controlled trials demonstrating increased survival or clinical benefit.

CONTRAINDICATIONS section:

Patients with EGFR negative tumours

IRESSA appears unlikely to benefit patients whose tumours have been tested and are shown to be EGFR-negative. EGFR-negative expression status was defined as having less than 10% of cells staining for EGFR using the DAKO EGFR pharmDx^TM kit.

The full ISEL dataset will be reviewed by Health Canada as a formal regulatory submission. The IRESSA label will be updated in an expedited manner. The updated Product Monograph is not available at the time of this publication.

Clarification from Health Canada regarding the status of IRESSA can be found on the Health Canada Web Site.

Any suspected adverse reaction can be reported to:

AstraZeneca Canada Inc.

1004 Middlegate Road

Mississauga, ON L4Y 1M4

Tel: 1-800-433-0733

Fax: 1-800-267-5743

http://www.astrazeneca.ca

Any suspected adverse reaction can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0701C

OTTAWA, Ontario, K1A 0K9

Tel: (613) 957-0337 or Fax: (613) 957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

For other inquiries, please refer to contact information:

Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS)

BMORS_Enquiries@hc-sc.gc.ca

Tel: (613) 941-3171

Fax: (613) 941-1365

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

Should you have any questions or require additional information regarding IRESSA^®, please contact AstraZeneca Medical Information at 1-800-668-6000 (English) and/or 1-800-461-3787 (French).

AstraZeneca Canada Inc.

original signed by

Kazimierz R. Borkowski, Ph.D.

Vice-President Medical Affairs

IRESSA^® and the AstraZeneca logo are trade-marks of the AstraZeneca group of companies.