September 21, 2005
Subject:     Celebrex* (celecoxib) capsules
Important Safety Information

http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/celebrex_3_hpc-cps_e.html

Dear Health Care Professional,

Pfizer Canada Inc., following discussions with Health Canada, would
like to inform you of important new safety information for CELEBREX*
(celecoxib) capsules. The Product Monograph for CELEBREX is being
revised as outlined below.

The revisions to the CELEBREX Product Monograph are based on Health
Canada's ongoing scientific review of the cardiovascular safety of
selective COX-2 inhibitor non-steroidal anti-inflammatory drugs
(NSAIDs).

Health Canada acknowledges that as a group, selective COX-2 inhibitor
NSAIDs are associated with an increased risk of cardiovascular events,
a risk that is similar to those associated with most NSAIDs and
consequently, will issue guidance to manufacturers, establishing
standards for the risk and benefit information that must be included in
product labelling of NSAIDs.

  1. INDICATIONS AND CLINICAL USE

     The INDICATIONS AND CLINICAL USE section has been revised to
include the following boxed statement:

     Randomized clinical trials with NSAIDs, including CELEBREX, have
not been designed to detect differences in cardiovascular adverse
events in a chronic setting (See CONTRAINDICATIONS and CLINICAL TRIALS
- Safety Studies).

     The decision to prescribe CELEBREX should be based on the
individual patient's overall risk (See CONTRAINDICATIONS and WARNINGS
AND PRECAUTIONS).

     Use of CELEBREX should be limited to the lowest effective dose
for the shortest possible duration of treatment.

  2. CONTRAINDICATIONS

     The CONTRAINDICATIONS section has been updated to include the
following boxed statements:

     Coronary Artery Bypass Graft Surgery

     CELEBREX is CONTRAINDICATED in the peri-operative setting of
coronary artery bypass surgery (CABG). Although CELEBREX has not been
studied in this patient population, another selective COX-2 inhibitor
NSAID studied in such a setting has led to an increased incidence of
cardiovascular/thromboembolic events, deep surgical infections and
sternal wound complications.

     Pregnancy (3rd Trimester), Breastfeeding
         * CELEBREX is CONTRAINDICATED for use during the third
trimester of pregnancy because of risk of premature closure of the
ductus arteriosus and uterine inertia (prolonged parturition).
         * CELEBREX is CONTRAINDICATED for use in women who are
breastfeeding because of the potential for serious adverse reactions in
nursing infants.

     (See Pregnant Women and Breast Feeding)

  3. WARNINGS AND PRECAUTIONS

     The following boxed statements have been added:

     Ischemic Heart Disease, Cerebrovascular Disease, Congestive Heart
Failure (NYHA II-IV)

     Caution should be exercised in prescribing CELEBREX to any
patient with ischemic heart disease (including but not limited to acute
myocardial infarction, history of myocardial infarction and/or angina),
cerebrovascular disease (including but not limited to stroke,
cerebrovascular accident, transient ischemic attacks and/or amaurosis
fugax) and/or congestive heart failure (NYHA II-IV).

     One of three randomized clinical trials of about 3 years duration
showed a dose-related increase in serious cardiovascular events (mainly
myocardial infarction), detectable at doses of CELEBREX 200 mg twice
daily or more, compared to placebo.

     The following text has also been added regarding the risk of
cardiovascular and thromboembolic events:

     Caution should be exercised in prescribing CELEBREX to patients
with risk factors for cardiovascular disease, cerebrovascular disease
or renal disease, such as any of the following (not an exhaustive list)
(See Clinical Trials - Safety Studies):

         * Hypertension
         * Dyslipidemia / Hyperlipidemia
         * Diabetes Mellitus
         * Congestive Heart Failure (NYHA I)
         * Coronary Artery Disease (Atherosclerosis)
         * Peripheral Arterial Disease
         * Smoking
         * Creatinine Clearance < 50 mL/min

  4. CLINICAL TRIALS

     The Clinical Trials section has been updated to include a
sub-section entitled Cardiovascular Safety - Ongoing Clinical Trials as
follows:

     Preliminary safety information from three long-term studies
involving patients with Sporadic Adenomatous Polyps or who were
predisposed to developing Alzheimer's disease treated with CELEBREX
is available. In one of the three studies, the APC (Prevention of
Sporadic Colorectal Adenomas with Celecoxib) study involving patients
with adenomatous polyps, there was a dose-related increase in
cardiovascular events (mainly myocardial infarction, MI) at CELEBREX
doses of 200 mg BID and 400 mg BID compared to placebo. The relative
risk (RR) for the composite endpoint (cardiovascular death, MI or
stroke) was 3.4 (95% CI 1.4 - 8.5) for the higher dose and 2.5 (95%
CI 1.0 - 6.4) for the lower dose of CELEBREX, compared to placebo.
The absolute risk for the composite endpoint was 3.0% for the higher
dose of CELEBREX, 2.2% for the lower dose of CELEBREX, and 0.9% for
placebo.

     Preliminary data from the other two long-term studies did not
show an increased cardiovascular risk with CELEBREX 200 mg BID and 400
mg QD compared to placebo. Data from one of these studies, PreSAP
(Randomized, Double Blind, Placebo - Controlled Study of the
     Efficacy and Safety of Celecoxib in the Prevention of Colorectal
Sporadic Adenomatous Polyps), a 36-month study in patients with a
history of sporadic adenomatous polyps, has not shown an increased
cardiovascular risk with CELEBREX 400 mg QD compared to placebo. Data
from the third study, ADAPT (Alzheimer's Disease Anti-Inflammatory
Prevention Trial), involving patients who were predisposed to
developing Alzheimer's disease (20 months average duration of
treatment), has not shown an increased cardiovascular risk with
CELEBREX 200 mg BID compared to placebo.

  5. OTHER - PREGNANCY AND BREASTFEEDING

     The following boxed statement has been added to the WARNINGS AND
PRECAUTIONS section:

     Risk in Pregnancy

     Caution should be exercised in prescribing CELEBREX during the
first and second trimesters of pregnancy. CELEBREX is CONTRAINDICATED
for use during the third trimester because of risk of premature closure
of the ductus arteriosus and uterine inertia (prolonged parturition).

     (See Contraindications, Pregnancy)

     CELEBREX continues to be indicated for the relief of symptoms
associated with osteoarthritis and adult rheumatoid arthritis. CELEBREX
may also be used for the short-term (one week or less) management of
moderate to severe pain in adults caused by conditions such as sprains,
surgery or tooth extractions.

     Physicians should consider this information in evaluating the
risks and benefits of CELEBREX in individual patients treated for OA,
RA or acute pain.

     The identification, characterization, and management of
drug-related adverse events are dependent on the active participation
of health care professionals in adverse drug reaction reporting
programmes. Healthcare professionals are asked to report any suspected
adverse reactions in patients receiving CELEBREX* to the following
addresses: