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FDA
Alert for Practitioners
Celecoxib (marketed as Celebrex)
FDA Alert:
4/7/2005:
Celebrex has
been associated with an increased risk of serious adverse
cardiovascular (CV) events in a long-term placebo controlled trial.
Based on the currently available data, FDA has concluded that an
increased risk of serious adverse CV events appears to be a class
effect of non-steroidal anti-inflammatory drugs (NSAIDs) (excluding
aspirin). FDA has requested that the package insert for all NSAIDs,
including Celebrex, be revised to include a boxed warning to
highlight the potential increased risk of CV events and the well
described risk of serious, and potentially life-threatening,
gastrointestinal bleeding. FDA has also requested that the package
insert for all NSAIDs be revised to include a contraindication for
use in patients immediately post-operative from coronary artery
bypass (CABG) surgery.
This information
reflects FDA’s current analysis of all available data concerning
this drug. FDA intends to update this sheet when additional
information or analyses become available.
Recommendations
-
Physicians are encouraged to carefully weigh the
potential benefits and risks of Celebrex and other treatment options
for the condition to be treated before a decision is made to use
Celebrex. If Celebrex is selected for an individual patient, FDA
encourages use of the lowest effective dose for the shortest
duration consistent with individual patient treatment goals.
-
Celebrex should not be used in patients who are
immediately post-operative from CABG surgery.
Data Summary
-
In the National Cancer Institute’s Adenoma
Prevention with Celecoxib (APC) trial in patients at risk for
recurrent colon polyps, a 2-3 fold increased risk of serious adverse
CV events was seen for Celebrex compared to placebo after a mean
duration of treatment of 33 months. There appeared to be a dose
response relationship, with a hazard ratio of 2.5 for Celebrex 200
mg twice daily and 3.4 Celebrex 400 mg twice daily for the composite
endpoint of death from CV causes, myocardial infarction (MI), or
stroke.
-
In the nearly identical Prevention of Spontaneous
Adenomatous Polyps (PreSAP) trial, the APC results were not
replicated. Based on preliminary, unpublished data presented by the
investigators at the February 16-18, 2005, FDA meeting of the
Arthritis Advisory Committee and the Drug Safety and Risk Management
Advisory Committee, the hazard ratio was 1.1 for celecoxib 400 mg
once daily compared to placebo for the composite endpoint of death
from CV causes, MI, or stroke. (Extensive data related to the
cardiovascular safety of Celebrex and other COX-2 selective and
non-selective NSAIDs were presented at this Advisory Committee
meeting. This information is available on the following website:
http://www.fda.gov/ohrms/dockets/ac/cder05.html#ArthritisDrugs).
-
Another long-term controlled trial, the National
Institute of Aging’s Alzheimer’s Disease Anti-Inflammatory Prevent
Trial (ADAPT), compared Celebrex 200 mg twice daily to placebo in
patients at risk for Alzheimer’s disease. Data are not yet available
from this trial; however, a preliminary report released by NIH on
December 20, 2004, (http://www.nih.gov/news/pr/dec2004/od-20.htm)
suggested that no increased risk of serious adverse CV events was
found for Celebrex compared to placebo.
-
The only available data from a long-term comparison
of Celebrex to other NSAIDs come from the Celebrex Long-Term
Arthritis Safety Study (CLASS) in which Celebrex 400 mg twice daily
was compared to diclofenac and ibuprofen in approximately 8,000
patients with osteoarthritis. No differences were observed for
serious adverse CV events between Celebrex and the two NSAID
comparators in this trial.
-
In two short-term placebo-controlled clinical trials
in patients immediately post-operative from CABG surgery, valdecoxib,
another COX-2 selective NSAID, was associated with an approximately
two-fold increased risk of serious adverse CV events compared to
placebo. No data are available for Celebrex in the post-CABG surgery
population; however, pending receipt of further data, FDA has
concluded that all NSAIDs, including Celebrex, should be
contraindicated in patients immediate post-operative from CABG
surgery.
Report serious adverse events to FDA's MedWatch at
1-800-FDA-1088; or
http://www.fda.gov/medwatch/report/hcp.htm
Questions? Call Drug Information, 1-888-INFO-FDA
(automated) or 301-827-4570
druginfo@fda.hhs.gov
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Date created: April 7, 2005 |
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