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Pages: 3, Size: 28.7 K, Date: 2004-06-22


The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

This is duplicated text of a letter from AstraZeneca Canada Inc.
Contact the company for a copy of any references, attachments or enclosures.



Health Canada Endorsed Important Safety Information on
Crestor® (rosuvastatin)



June 15th, 2004

Subject: Association of Crestor® (rosuvastatin) with rhabdomyolysis

Dear Health Care Professional,

AstraZeneca, after discussion with Health Canada, would like to inform you of important safety information regarding the association between Crestor® (rosuvastatin) and rhabdomyolysis.

Rosuvastatin has been associated with post-market reports of rhabdomyolysis in Canada. Internationally, all statins have been associated with rhabdomyolysis.


The occurrence of muscle-related adverse events during statin therapy may be related to the statin dose. In Canada, of the eight reported cases of rhabdomyolysis with rosuvastatin, two cases occurred at the 10 mg daily starting dose, five cases at 40 mg, and in one case the dose was not specified.


All of the Canadian reported cases were associated with predisposing risk factors. Therefore, caution should be exercised when prescribing rosuvastatin in patients with pre-existing risk factors or concomitant medications which pose increased risk for statin induced myopathy or rhabdomyolysis.


AstraZeneca has recently distributed Dear Health Care Professional Letters in the UK and Europe to advise of patients presenting with rhabdomyolysis while under treatment with Crestor® (rosuvastatin). Those communications referred to cases occurring in patients with rosuvastatin therapy initiated at higher than the recommended starting dose of 10 mg daily.
The US Food and Drug Administration (FDA) has issued a Public Health Advisory advising US physicians to adhere to the prescribing guidelines outlined in the current FDA approved product monograph when prescribing Crestor®, in order to minimize risk of myopathy.

Rosuvastatin is a lipid lowering agent of the statin class and was introduced onto the Canadian market in February 2003. In the Canadian Adverse Drug Reactions Monitoring Program (CADRMP) database, there are 8 Canadian post-market cases of rhabdomyolysis associated with rosuvastatin. Five cases occurred with rosuvastatin 40 mg daily, 2 cases have occurred at the 10 mg usual recommended starting daily dose, and for the remaining case the dose was not specified. The involved patients all had one or more pre-existing risk factors for statin induced myotoxicity. Of the cases occurring at the 10 mg dose the pre-existing risk factors for myotoxicity were: chronic renal insufficiency in one patient and prior experience of myalgia while on another statin in the other, with other factors, including possible polymyositis, still under investigation.

Some patients are at higher risk for statin induced myopathy or rhabdomyolysis. Identifiable predisposing risk factors for statin therapy include the following:

renal impairment
hypothyroidism
personal or family history of hereditary muscular disorders
previous history of muscular toxicity with another statin or fibrate
alcohol abuse
situations where an increase in plasma levels may occur
Japanese and Chinese patients
concomitant use of fibrates
Caution should be exercised when prescribing all statins in patients presenting any of the above risk factors or concomitant medications. Close supervision and monitoring is recommended.

The occurrence of muscle-related adverse events during statin therapy may be dose related. When prescribing rosuvastatin, as with all statins, patients should be started at the recommended starting dose(s) and titrated to the lowest effective dose. The highest marketed dose should only be considered in patients with significant cardiovascular risk, who do not achieve their treatment goal at lower doses, and careful follow-up is required.

Prescribers of rosuvastatin, as with all statins, should maintain an increased level of awareness of the potential for muscle toxicity and rhabdomyolysis. Concerning features include unexplained musculoskeletal pain and/or muscle weakness, elevated creatine kinase, elevated creatinine, myoglobinemia, myoglobinuria or brown or “cola” coloured urine.

All patients should be advised to report muscle pain, muscle weakness or cramps, or discoloured urine to their physician immediately. Creatine kinase measurements should be performed when symptoms occur. Rosuvastatin, as with all statins, should be discontinued immediately if myopathy is suspected or diagnosed, or if CK elevation is greater than 10X the upper limit of normal (ULN).

Health Canada will continue to monitor the safety profile of statins, including rosuvastatin, and will examine new safety information as it emerges. Meanwhile, it is important to remain vigilant for the possibility of muscle toxicity and to report any possible cases. Health Canada will also review the data submitted by AstraZeneca and will determine the need for product labelling changes.

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. Any occurrences of rhabdomyolysis or other serious and/or unexpected adverse reactions in patients receiving Crestor® should be reported to AstraZeneca or Health Canada at the following addresses:

AstraZeneca Canada Inc.
1004 Middlegate Road
Mississauga, ON, L4Y 1M4
Tel: 1-800-433-0733
Fax: 1-800-267-5743
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.

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.


If you have any questions in regards to this information, 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