Archive – Safety and regulatory information regarding Celebrex (celecoxib), Bextra (valdecoxib), and Meloxicam subsequent to the withdrawl of Vioxx (rofecoxib)

Starting date:

September 30, 2004

Posting date:

September 30, 2004

Type of communication:

Advisory

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

New safety information, Product Safety

Audience:

General Public

Identification number:

RA-11000217

This fact sheet provides easy access for healthcare professionals and patients to regulatory and safety information on Health Canada's website about selective COX-2 inhibitor NSAIDs (non-steroidal anti-inflammatory drugs) authorized for sale in Canada, namely:

• celecoxib (under the brand name Celebrex^®) and valdecoxib (under the brand name Bextra™), which are marketed in Canada by Pfizer Canada Inc., and
• meloxicam, which is marketed by Boehringer Ingelheim (Canada) Ltd. under the brand name Mobicox^® and as a generic by Ratiopharm Inc., Pharmascience Inc., Dominion Pharmacal, Pharmel Inc., Apotex Inc., Cobalt Pharmaceutical Inc., Genpharm Inc., and Novopharm NSAID

On September 30, 2004, Merck Frosst Canada Inc., voluntarily withdrew Vioxx^® (rofecoxib) from the Canadian market due to safety concerns related to an increased risk of heart attack and stroke. Vioxx^®, a non-steroidal anti-inflammatory drug (NSAID), is a selective COX-2 inhibitor, which had been approved in Canada for the treatment of acute and chronic symptoms of osteoarthritis, rheumatoid arthritis, and acute pain.

Benefits and risks

As with any treatment, patients should discuss all benefits and risks with their physicians. Risks associated with the use of a health product arise from several factors, including the properties of the product itself, the disease or condition being treated, the combination with other health products, unpredictable allergic and other individual reactions to a product, inappropriate use of the product, or underlying individual genetic makeup that may predispose to certain reactions. Each individual's situation must be assessed by the appropriate health care provider to ensure that an acceptable benefit to risk profile exists before the product has been prescribed. There are often a number of risks and benefits that need to be determined and discussed in each individual's case.

Risk of heart attack and stroke

Vioxx was withdrawn primarily because of new information about an increased risk of heart attack (myocardial infarction) and stroke (cerebrovascular accident). This type of safety risk was demonstrated as a result of recent analysis of the Adenomatous Polyp Prevention of VIOXX (APPROVe) clinical trial conducted by Merck.

The results of clinical trials with one drug in a given group do not necessarily apply to other drugs in the same group. Post-market surveillance of selective COX-2 inhibitor NSAIDs is ongoing by Health Canada as well as internationally. In light of the APPROVe trial, Health Canada has convened a team of internal experts to review worldwide safety data, and is in communication with regulatory agencies in other countries, in order to provide healthcare professionals and the public with up-to-date and reliable information on which to base informed choices about treatment.

Safety information on selective COX-2 inhibitor NSAIDS

Safety information for the public and healthcare professionals on selective COX-2 inhibitor NSAIDs is available on the Health Canada website as follows.

Public advisories

Advisory, warning and recall notices issued more than 7 years ago have been removed from the Health Canada Web site; however, the titles and the dates of these notices remain. If you wish to access any of these past notices, you can contact us at info@hc-sc.gc.ca.

• Important Savety Information for Patients Taking Vioxx^® (rofecoxib) April 19, 2002
• Important Safety Information for Patients Taking Celebrex^® (celecoxib) May 23, 2002

Dear Healthcare Professional letters

• Important Safety Information Regarding Bextra™ (valdecoxib) Dec 31, 2002
• Important Drug Safety Information on Vioxx®(rofecoxib) April 15, 2002
• Important Drug Safety Information on Celebrex^® (celecoxib) May 13, 2002

Canadian Adverse Reaction Newsletter articles

• Celecoxib (Celebrex^®): 1 year later – April 2000
• Rofecoxib, a year in review – April 2001
• Selective Cox-2 inhibitors – April 2002
• Valdecoxib (Bextra™): severe cutaneous reactions – January 2004

Regulatory information

Health Canada has been looking at post-market information about cardiovascular events as they relate to Vioxx^® and other selective COX-2 inhibitor NSAIDS since 2000.

In January, 2002, Health Canada convened its Expert Advisory Committee on Pharmacovigilance (pharmacological vigilance ) for advice on the cardiovascular risks of selective COX-2 inhibitor NSAIDs. The Committee discussed only Vioxx®, Celebrex®, and Mobicox®, since Bextra™ was not on the market at that time. The Committee did not rule out the possibility that all selective COX-2 inhibitor NSAIDs could present some cardiovascular risk. The debate is ongoing in scientific circles. The minutes of the Committee meeting are available at:

• Advisory Committee on Pharmacovigilance

As a result of the meeting, the following safety information was issued:

• Public Advisory on Vioxx^® (April, 2002)
• Article in the Canadian Adverse Reaction Newsletter on COX-2 inhibitors (April, 2002)
• Dear Health Care Professional Letter by Merck Frosst Canada Inc. regarding Vioxx^® (April, 2002)
• Public Advisory on Celebrex^® (May, 2002)
• Dear Health Care Professional Letter by Pharmacia Canada Inc and Pfizer Canada (May, 2002)

Celecoxib

Celebrex^® (celecoxib) was approved in 1999 as an anti-inflammatory and pain reliever for acute and chronic use in relieving the symptoms of osteoarthritis and rheumatoid arthritis in adults. In 2002, Celebrex® was granted market authorization with conditions for use in the reduction of abnormal growth of tissue in the large intestine (adenomatous colorectal polyps), which may lead to colon cancer in patients with a family history of such growths.

In 2004, Celebrex^® (celecoxib) was approved for the short-term (seven days or less) management of moderate-to-severe acute pain in adults.

Meloxicam

Meloxicam was approved in 2000 as an anti-inflammatory and pain reliever for treatment of the symptoms of rheumatoid arthritis and painful osteoarthritis in adults. It is currently authorized for marketing in Canada under a number of different names:Mobicox^® (meloxicam), Ratio-Meloxicam, PMS-Meloxicam, Dom-Meloxicam, PHL-Meloxicam, APO- Meloxicam, CO-Meloxicam, GEN-Meloxicam, and NOVO-Meloxicam.

Valdecoxib

Bextra™ (valdecoxib) is used for acute and chronic treatment of the symptoms of adult rheumatoid arthritis and osteoarthritis, as well as relief of menstrual pain (primary dysmenorrhea). Bextra^® (valdecoxib) was approved for marketing in Canada in December 2002.

At the time of market introduction, at Health Canada's request, the drug's market authorization holder issued a letter to healthcare professionals regarding safety information pertaining to adverse skin reactions, which had been reported at that time in other countries where Bextra™ (valdecoxib) was marketed.

Recent post-market experience indicates that the reported rate of serious skin reactions with Bextra™ appears to be greater than for other selective COX-2 inhibitor NSAIDs. An article in the January 2004, Canadian Adverse Reaction Newsletter (CARN) advises healthcare professionals about severe adverse skin reactions associated with Bextra™ (valdecoxib).

Ongoing assessment of selective COX-2 inhibitor NSAIDs

Health Canada is continuing its post-market surveillance of selective COX-2 inhibitor NSAIDs. In October, 2004, Health Canada requested the market authorization holders (Pfizer Canada Inc., Boehringer Ingelheim (Canada) Inc., and the manufacturers of generic meloxicam) to supply worldwide data on safety in general and cardiovascular safety in particular for Celebrex^®, Bextra™, Mobicox^® and generic meloxicam, with a view to updating the prescribing information. Health Canada's team of internal and external experts will conduct a thorough review of this material and will communicate with other international regulatory agencies on this issue.

Health Canada will continue to inform the public and healthcare professionals of new relevant safety information.

Note: Health Canada issued another advisory on this topic on April 7, 2005. To access this advisory, visit: Health Canada has asked Pfizer to suspend sales of its drug Bextra™ and informs canadians of new restrictions on the use of Celebrex^MD.