Important Safety Information on Oxeze (formoterol fumarate dihydrate) Turbuhaler – AstraZeneca Canada Inc. – For Health Professionals

Health Canada Endorsed Important Safety Information on Oxeze (formoterol fumarate dihydrate) Turbuhaler

September 7, 2005

Subject: Updated safety information regarding the US FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC) meeting to review the safety of the long-acting beta agonists

Dear Health Care Professional,

AstraZeneca Canada Inc. in consultation with Health Canada would like to update you on the outcomes of the US FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC) meeting held on July 13, 2005 to review the safety of the long-acting beta agonists salmeterol and formoterol.

Data from a large placebo controlled US study, the Salmeterol Multi-Center Asthma Research Trial, conducted by GlaxoSmithKline, that compared the safety of salmeterol or placebo added to the patient's usual asthma therapy showed increased risks of asthma related death and other serious respiratory related outcomes in patients receiving salmeterol. Post hoc analysis of the data suggests the risks may be greater in patients who did not report using ICSs at study entry and in African-American patients. Although similar data for formoterol is not available at this time, the increased risks may apply not only to salmeterol but also to the other long-acting beta-2-agonist asthma medications such as formoterol.

In extensive clinical trials in over 28,000 patients or during the post-marketing experience of over 2.7 million treatment years, these effects have not been seen with Oxeze^®. The data for Oxeze^® were not included in the US review and AstraZeneca did not participate in the PADAC meeting. The PADAC unanimously agreed that formoterol and salmeterol should continue to be commercially available as a treatment option for patients with asthma.

Oxeze^® is indicated for the treatment and prevention of symptoms of reversible obstructive airways disease including asthma in patients 6 years of age and older^{Footnote 1}.

Important Advice for Managing your Patients

AstraZeneca believes it is important to reiterate and reinforce advice for the management of patients established in the Canadian Asthma Consensus Guidelines^{Footnote 2},^{Footnote 3} and current prescribing information for Oxeze^® Turbuhaler^®.

• Patients with asthma should be receiving optimal anti-inflammatory therapy with corticosteroids before starting maintenance treatment with Oxeze^® Turbuhaler^®. Maintenance treatment with formoterol is not a substitute for inhaled or oral corticosteroids; its use is complementary to them. Patients must be advised not to stop or reduce corticosteroid therapy without medical advice.
• Oxeze^® Turbuhaler^® can be used on demand to treat acute symptoms in patients 12 years and older, however, medical attention should be sought if patients find that relief bronchodilator treatment becomes less effective or that they need more inhalations than usual.
• Increasing use of Oxeze^® Turbuhaler^® or other fast-acting bronchodilators to control symptoms indicates deterioration of asthma control and the need to reassess the patient's therapy, particularly the requirements for adequate anti-inflammatory medication.
• The dosage should not be increased beyond the maximum recommended dose. The dose of Oxeze^® Turbuhaler^® should be individualized to the patient's needs and should be the lowest possible dose that keeps the patient symptom free or fulfills the therapeutic objective.
• Patients should be educated to recognize the signs of deteriorating asthma control and the need to seek medical attention promptly in such circumstances.

The review of the safety of formoterol is ongoing at Health Canada and further action may be taken if necessary.

AstraZeneca continuously monitors the safety of Oxeze^®, and our other products, as part of our routine safety monitoring. The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Health care professionals are asked to report any suspected adverse reactions in patients receiving Oxeze^® Turbuhaler^® (formoterol fumarate dihydrate) and Symbicort^® Turbuhaler^® (budesonide/formoterol fumarate dihydrate) to AstraZeneca or Health Canada at the following addresses:

AstraZeneca Canada Inc.

1004 Middlegate Road

Mississauga, Ontario

L4Y 1M4

Tel: 1-800-433-0733

Fax: 1-800-267-5743

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 Cardiology, Allergy and Neurological Sciences (BCANS)

BCANS_Enquiries@hc-sc.gc.ca

Tel: (613) 941-1499

Fax: (613) 941-1668

he 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.

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

If you have any questions regarding this information, please contact AstraZeneca Medical Information at 1-800-668-6000 (English) and/or 1-800-461-3787 (French).

Sincerely,

AstraZeneca Canada Inc.

original signed by

Kazimierz R. Borkowski, Ph.D.

Vice President, Medical Affairs

Oxeze^®, Symbicort^®, Turbuhaler^®, and the AstraZeneca logo are trade-marks of the AstraZeneca group of companies.

References

Footnote 1

Canadian Product Monograph for Oxeze^® Turbuhaler^® (formoterol fumarate dihydrate). AstraZeneca Canada Inc. Date of Revision: January 7, 2004

Return to footnote 1 referrer

Footnote 2

Canadian Asthma Consensus Report. CMAJ 1999;161 (11 Suppl)

Return to footnote 2 referrer

Footnote 3

Adult Asthma Consensus Guidelines Update 2003. Can Respir J 2004;11(Suppl A):9A-18A

Return to footnote 3 referrer