Cardiovascular Thrombotic Events
Chronic use of CELEBREX may cause an increased risk of serious adverse cardiovascular
thrombotic events, myocardial infarction, and stroke, which can be fatal.
In the APC (Adenoma Prevention with Celecoxib) trial, the hazard ratio for
the composite endpoint of cardiovascular death, MI, or stroke was 3.4 (95%
CI 1.4 – 8.5) for CELEBREX 400 mg twice daily and 2.8 (95% CI 1.1 – 7.2)
with CELEBREX 200 mg twice daily compared to placebo. Cumulative rates for
this composite endpoint over 3 years were 3.0% (20/671 subjects) and 2.5%
(17/685 subjects), respectively, compared to 0.9% (6/679 subjects) with
placebo treatment. The increases in both celecoxib dose groups versus placebo-treated
patients were mainly due to an increased incidence of myocardial infarction
(
see Clinical Studies).
All NSAIDs, both COX-2 selective and non-selective, may have a similar
risk. Patients with known CV disease or risk factors for CV disease may
be at greater risk. To minimize the potential risk for an adverse CV event
in patients treated with CELEBREX, the lowest effective dose should be used
for the shortest duration consistent with individual patient treatment goals.
Physicians and patients should remain alert for the development of such
events, even in the absence of previous CV symptoms. Patients should be
informed about the signs and/or symptoms of serious CV toxicity and the
steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates
the increased risk of serious CV thrombotic events associated with NSAID
use. The concurrent use of aspirin and CELEBREX does increase the risk of
serious GI events (see Warnings and Precautions).
Two large, controlled, clinical trials of a different COX-2 selective
NSAID for the treatment of pain in the first 10-14 days following CABG surgery
found an increased incidence of myocardial infarction and stroke (see
Contraindications).
Hypertension
As with all NSAIDs, CELEBREX can lead to the onset of new hypertension or
worsening of preexisting hypertension, either of which may contribute to
the increased incidence of CV events. Patients taking thiazides or loop
diuretics may have impaired response to these therapies when taking NSAIDs.
NSAIDs, including CELEBREX, should be used with caution in patients with
hypertension. Blood pressure should be monitored closely during the initiation
of therapy with CELEBREX and throughout the course of therapy. The rates
of hypertension from the CLASS trial in the CELEBREX, ibuprofen and diclofenac-treated
patients were 2.4%, 4.2% and 2.5%, respectively (see Clinical Studies).
Congestive Heart Failure and Edema
Fluid retention and edema have been observed in some patients taking NSAIDs,
including CELEBREX (see Adverse Reactions). In the CLASS study (see
Clinical Studies), the Kaplan-Meier cumulative rates at 9 months of
peripheral edema in patients on CELEBREX 400 mg twice daily (4-fold and
2-fold the recommended OA and RA doses, respectively, and the approved dose
for FAP), ibuprofen 800 mg three times daily and diclofenac 75 mg twice
daily were 4.5%, 6.9% and 4.7%, respectively. CELEBREX should be used with
caution in patients with fluid retention or heart failure.
Gastrointestinal (GI) Effects
Risk of GI Ulceration, Bleeding, and Perforation
NSAIDs, including CELEBREX, can cause serious gastrointestinal events including
bleeding, ulceration, and perforation of the stomach, small intestine or
large intestine, which can be fatal. These serious adverse events can occur
at any time, with or without warning symptoms, in patients treated with
NSAIDs. Only one in five patients who develop a serious upper GI adverse
event on NSAID therapy is symptomatic. Complicated and symptomatic ulcer
rates were 0.78% at nine months for all patients in the CLASS trial, and
2.19% for the subgroup on low dose ASA. Patients 65 years of age and older
had an incidence of 1.40% at nine months, 3.06% when also taking ASA (see
Clinical Studies). With longer duration of use of NSAIDs, there is a
trend for increasing the likelihood of developing a serious GI event at
some time during the course of therapy. However, even short-term therapy
is not without risk.
NSAIDs should be prescribed with extreme caution in patients with a prior
history of ulcer disease or gastrointestinal bleeding. Patients with a prior
history of peptic ulcer disease and/or gastrointestinal bleeding who use
NSAIDs have a greater than 10-fold increased risk for developing a GI bleed
compared to patients with neither of these risk factors. Other factors that
increase the risk of GI bleeding in patients treated with NSAIDs include
concomitant use of oral corticosteroids or anticoagulants, longer duration
of NSAID therapy, smoking, use of alcohol, older age, and poor general health
status. Most spontaneous reports of fatal GI events are in elderly or debilitated
patients and therefore special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event, the lowest effective
dose should be used for the shortest duration consistent with individual
patient treatment goals. Physicians and patients should remain alert for
signs and symptoms of GI ulceration and bleeding during CELEBREX therapy
and promptly initiate additional evaluation and treatment if a serious GI
adverse event is suspected. For high-risk patients, alternate therapies
that do not involve NSAIDs should be considered.
Hepatic Effects
Borderline elevations of one or more liver-associated enzymes may occur
in up to 15% of patients taking NSAIDs, and notable elevations of ALT or
AST (approximately 3 or more times the upper limit of normal) have been
reported in approximately 1% of patients in clinical trials with NSAIDs.
These laboratory abnormalities may progress, may remain unchanged, or may
be transient with continuing therapy. Rare cases of severe hepatic reactions,
including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic
failure (some with fatal outcome) have been reported with NSAIDs, including
CELEBREX (see Adverse Reactions). In controlled clinical trials of
CELEBREX, the incidence of borderline elevations (greater than or equal
to 1.2 times and less than 3 times the upper limit of normal) of liver associated
enzymes was 6% for CELEBREX and 5% for placebo, and approximately 0.2% of
patients taking CELEBREX and 0.3% of patients taking placebo had notable
elevations of ALT and AST.
A patient with symptoms and/or signs suggesting liver dysfunction, or
in whom an abnormal liver test has occurred, should be monitored carefully
for evidence of the development of a more severe hepatic reaction while
on therapy with CELEBREX. If clinical signs and symptoms consistent with
liver disease develop, or if systemic manifestations occur (e.g., eosinophilia,
rash, etc.), CELEBREX should be discontinued.
Renal Effects
Long-term administration of NSAIDs has resulted in renal papillary necrosis
and other renal injury. Renal toxicity has also been seen in patients in
whom renal prostaglandins have a compensatory role in the maintenance of
renal perfusion. In these patients, administration of an NSAID may cause
a dose-dependent reduction in prostaglandin formation and, secondarily,
in renal blood flow, which may precipitate overt renal decompensation. Patients
at greatest risk of this reaction are those with impaired renal function,
heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors,
angiotensin II receptor antagonists, and the elderly. Discontinuation of
NSAID therapy is usually followed by recovery to the pretreatment state.
Clinical trials with CELEBREX have shown renal effects similar to those
observed with comparator NSAIDs.
No information is available from controlled clinical studies regarding
the use of CELEBREX in patients with advanced renal disease. Therefore,
treatment with CELEBREX is not recommended in these patients with advanced
renal disease. If CELEBREX therapy must be initiated, close monitoring of
the patient's renal function is advisable.
Anaphylactoid Reactions
As with NSAIDs in general, anaphylactoid reactions have occurred in patients
without known prior exposure to CELEBREX. In post-marketing experience,
rare cases of anaphylactic reactions and angioedema have been reported in
patients receiving CELEBREX. CELEBREX should not be given to patients with
the aspirin triad. This symptom complex typically occurs in asthmatic patients
who experience rhinitis with or without nasal polyps, or who exhibit severe,
potentially fatal bronchospasm after taking aspirin or other NSAIDs (see
Contraindications, Warnings and Precautions). Emergency help should
be sought in cases where an anaphylactoid reaction occurs.
Skin Reactions
CELEBREX is a sulfonamide and can cause serious skin adverse events such
as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal
necrolysis (TENS), which can be fatal. These serious events can occur without
warning and in patients without prior known sulfa allergy. Patients should
be informed about the signs and symptoms of serious skin manifestations
and use of the drug should be discontinued at the first appearance of skin
rash or any other sign of hypersensitivity.
Pregnancy
In late pregnancy, starting at 30 weeks gestation, CELEBREX should be avoided
because it may cause premature closure of the ductus arteriosus (see
Use in Specific Populations).
Corticosteroid Treatment
CELEBREX cannot be expected to substitute for corticosteroids or to treat
corticosteroid insufficiency. Abrupt discontinuation of corticosteroids
may lead to exacerbation of corticosteroid-responsive illness. Patients
on prolonged corticosteroid therapy should have their therapy tapered slowly
if a decision is made to discontinue corticosteroids.
Hematological Effects
Anemia is sometimes seen in patients receiving CELEBREX. In controlled clinical
trials the incidence of anemia was 0.6% with CELEBREX and 0.4% with placebo.
Patients on long-term treatment with CELEBREX should have their hemoglobin
or hematocrit checked if they exhibit any signs or symptoms of anemia or
blood loss. CELEBREX does not generally affect platelet counts, prothrombin
time (PT), or partial thromboplastin time (PTT), and does not inhibit platelet
aggregation at indicated dosages (see Clinical Pharmacology).
Disseminated Intravascular Coagulation (DIC)
CELEBREX should be used only with caution in pediatric patients with systemic
onset JRA due to the risk of disseminated intravascular coagulation.
Preexisting Asthma
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin
in patients with aspirin-sensitive asthma has been associated with severe
bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm,
between aspirin and other nonsteroidal anti-inflammatory drugs has been
reported in such aspirin-sensitive patients, CELEBREX should not be administered
to patients with this form of aspirin sensitivity and should be used with
caution in patients with preexisting asthma.
Laboratory Tests
Because serious GI tract ulcerations and bleeding can occur without warning
symptoms, physicians should monitor for signs or symptoms of GI bleeding.
Patients on long-term treatment with NSAIDs should have a CBC and a chemistry
profile checked periodically. If abnormal liver tests or renal tests persist
or worsen, CELEBREX should be discontinued.
In controlled clinical trials, elevated BUN occurred more frequently
in patients receiving CELEBREX compared with patients on placebo. This laboratory
abnormality was also seen in patients who received comparator NSAIDs in
these studies. The clinical significance of this abnormality has not been
established.
GI Cancer in Familial Adenomatous Polyposis
Treatment with CELEBREX in FAP has not been shown to reduce the risk of
gastrointestinal cancer or the need for prophylactic colectomy or other
FAP-related surgeries. Therefore, the usual care of FAP patients should
not be altered because of the concurrent administration of CELEBREX. In
particular, the frequency of routine endoscopic surveillance should not
be decreased and prophylactic colectomy or other FAP-related surgeries should
not be delayed.
Inflammation
The pharmacological activity of CELEBREX in reducing inflammation, and possibly
fever, may diminish the utility of these diagnostic signs in detecting infectious
complications of presumed noninfectious, painful conditions.
Concomitant NSAID Use
The concomitant use of CELEBREX with any dose of a non-aspirin NSAID should
be avoided due to the potential for increased risk of adverse reactions.
DRUG INTERACTIONS
General: Celecoxib metabolism is predominantly mediated via cytochrome
P450 (CYP) 2C9 in the liver. Co-administration of celecoxib with drugs that
are known to inhibit CYP2C9 should be done with caution. Significant interactions
may occur when celecoxib is administered together with drugs that inhibit
CYP2C9.
In vitro studies indicate that celecoxib, although not a substrate,
is an inhibitor of CYP2D6. Therefore, there is a potential for an in
vivo drug interaction with drugs that are metabolized by CYP2D6.
Warfarin
Anticoagulant activity should be monitored, particularly in the first few
days, after initiating or changing CELEBREX therapy in patients receiving
warfarin or similar agents, since these patients are at an increased risk
of bleeding complications. The effect of celecoxib on the anticoagulant
effect of warfarin was studied in a group of healthy subjects receiving
daily 2-5 mg doses of warfarin. In these subjects, celecoxib did not alter
the anticoagulant effect of warfarin as determined by prothrombin time.
However, in post-marketing experience, serious bleeding events, some of
which were fatal, have been reported, predominantly in the elderly, in association
with increases in prothrombin time in patients receiving CELEBREX concurrently
with warfarin.
Lithium
In a study conducted in healthy subjects, mean steady-state lithium plasma
levels increased approximately 17% in subjects receiving lithium 450 mg
twice daily with CELEBREX 200 mg twice daily as compared to subjects receiving
lithium alone. Patients on lithium treatment should be closely monitored
when CELEBREX is introduced or withdrawn.
Aspirin
CELEBREX can be used with low-dose aspirin. However, concomitant administration
of aspirin with CELEBREX increases the rate of GI ulceration or other complications,
compared to use of CELEBREX alone (see Warnings and Precautions and Clinical
Studies). Because of its lack of platelet effects, CELEBREX is not
a substitute for aspirin for cardiovascular prophylaxis (see Clinical
Pharmacology).
ACE-inhibitors and Angiotensin II Antagonists
Reports suggest that NSAIDs may diminish the antihypertensive effect of
Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin II antagonists.
This interaction should be given consideration in patients taking CELEBREX
concomitantly with ACE-inhibitors and angiotensin II antagonists (see
Clinical Pharmacology).
Fluconazole
Concomitant administration of fluconazole at 200 mg once daily resulted
in a two-fold increase in celecoxib plasma concentration. This increase
is due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole
(see Clinical Pharmacology). CELEBREX should be introduced at the
lowest recommended dose in patients receiving fluconazole.
Furosemide
Clinical studies, as well as post-marketing observations, have shown that
NSAIDs can reduce the natriuretic effect of furosemide and thiazides in
some patients. This response has been attributed to inhibition of renal
prostaglandin synthesis.
Methotrexate
In an interaction study of rheumatoid arthritis patients taking methotrexate,
CELEBREX did not have an effect on the pharmacokinetics of methotrexate
(see Clinical Pharmacology).
Concomitant NSAID Use
The concomitant use of CELEBREX with any dose of a non-aspirin NSAID should
be avoided due to the potential for increased risk of adverse reactions.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C. Pregnancy category D from 30 weeks of gestation onward.
Teratogenic effects: Celecoxib at oral doses ≥150 mg/kg/day
(approximately 2-fold human exposure at 200 mg twice daily as measured by
AUC0-24), caused an increased incidence of ventricular
septal defects, a rare event, and fetal alterations, such as ribs fused,
sternebrae fused and sternebrae misshapen when rabbits were treated throughout
organogenesis. A dose-dependent increase in diaphragmatic hernias was observed
when rats were given celecoxib at oral doses ≥30 mg/kg/day (approximately
6-fold human exposure based on the AUC0-24 at
200 mg twice daily) throughout organogenesis. There are no studies in pregnant
women. CELEBREX should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nonteratogenic effects: Celecoxib produced pre-implantation
and post-implantation losses and reduced embryo/fetal survival in rats at
oral dosages ≥50 mg/kg/day (approximately 6-fold human exposure based on
the AUC0-24 at 200 mg twice daily). These changes
are expected with inhibition of prostaglandin synthesis and are not the
result of permanent alteration of female reproductive function, nor are
they expected at clinical exposures. No studies have been conducted to evaluate
the effect of celecoxib on the closure of the ductus arteriosus in humans.
Therefore, use of CELEBREX during the third trimester of pregnancy should
be avoided.
Labor and Delivery
Celecoxib produced no evidence of delayed labor or parturition at oral doses
up to 100 mg/kg in rats (approximately 7-fold human exposure as measured
by the AUC0-24 at 200 mg BID). The effects of
CELEBREX on labor and delivery in pregnant women are unknown.
Nursing Mothers
Limited data from 3 published reports that included a total of 12 breastfeeding
women showed low levels of CELEBREX in breast milk. The calculated average
daily infant dose was 10-40 mcg/kg/day, less than 1% of the weight-based
therapeutic dose for a two-year old-child. A report of two breastfed infants
17 and 22 months of age did not show any adverse events. Caution should
be exercised when CELEBREX is administered to a nursing woman.
Pediatric Use
CELEBREX is approved for relief of the signs and symptoms of Juvenile Rheumatoid
Arthritis in patients 2 years and older. Safety and efficacy have not been
studied beyond six months in children. The long-term cardiovascular toxicity
in children exposed to CELEBREX has not been evaluated and it is unknown
if long-term risks may be similar to that seen in adults exposed to CELEBREX
or other COX-2 selective and non-selective NSAIDs (see Boxed Warning,
Warnings and Precautions, and Clinical Studies).
The use of celecoxib in patients 2 years to 17 years of age with pauciarticular,
polyarticular course JRA or in patients with systemic onset JRA was studied
in a 12-week, double-blind, active controlled, pharmacokinetic, safety and
efficacy study, with a 12-week open-label extension. Celecoxib has not been
studied in patients under the age of 2 years, in patients with body weight
less than 10 kg (22 lbs), and in patients with active systemic features.
Patients with systemic onset JRA (without active systemic features) appear
to be at risk for the development of abnormal coagulation laboratory tests.
In some patients with systemic onset JRA, both celecoxib and naproxen were
associated with mild prolongation of activated partial thromboplastin time
(APTT) but not prothrombin time (PT). NSAIDs including celecoxib should
be used only with caution in patients with systemic onset JRA, due to the
risk of disseminated intravascular coagulation. Patients with systemic onset
JRA should be monitored for the development of abnormal coagulation tests
(see Dosage and Administration, Warnings and Precautions, Adverse Reactions,
Animal Toxicology, Clinical Studies).
Alternative therapies for treatment of JRA should be considered in pediatric
patients identified to be CYP2C9 poor metabolizers (see Poor Metabolizers
of CYP2C9 substrates).
Geriatric Use
Of the total number of patients who received CELEBREX in pre-approval clinical
trials, more than 3,300 were 65-74 years of age, while approximately 1,300
additional patients were 75 years and over. No substantial differences in
effectiveness were observed between these subjects and younger subjects.
In clinical studies comparing renal function as measured by the GFR, BUN
and creatinine, and platelet function as measured by bleeding time and platelet
aggregation, the results were not different between elderly and young volunteers.
However, as with other NSAIDs, including those that selectively inhibit
COX-2, there have been more spontaneous post-marketing reports of fatal
GI events and acute renal failure in the elderly than in younger patients
(see Warnings and Precautions).
Hepatic Insufficiency
The daily recommended dose of CELEBREX capsules in patients with moderate
hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use
of CELEBREX in patients with severe hepatic impairment is not recommended
(see Dosage and Administration and Clinical Pharmacology).
Renal Insufficiency
CELEBREX is not recommended in patients with severe renal insufficiency
(see Warnings and Precautions and Clinical Pharmacology).
Poor Metabolizers of CYP2C9 Substrates
Patients who are known or suspected to be poor CYP2C9 metabolizers based
on previous history/experience with other CYP2C9 substrates (such as warfarin,
phenytoin) should be administered celecoxib with caution. Consider starting
treatment at half the lowest recommended dose. Alternative management should
be considered in JRA patients identified to be CYP2C9 poor metabolizers.
(see Dosage and Administration and Clinical Pharmacology).
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Celecoxib was not carcinogenic in rats given oral doses up to 200 mg/kg
for males and 10 mg/kg for females (approximately 2-to 4-fold the human
exposure as measured by the AUC0-24 at 200 mg
twice daily) or in mice given oral doses up to 25 mg/kg for males and 50
mg/kg for females (approximately equal to human exposure as measured by
the AUC0-24 at 200 mg twice daily) for two years.
Celecoxib was not mutagenic in an Ames test and a mutation assay in Chinese
hamster ovary (CHO) cells, nor clastogenic in a chromosome aberration assay
in CHO cells and an in vivo micronucleus test in rat bone marrow.
Celecoxib did not impair male and female fertility in rats at oral doses
up to 600 mg/kg/day (approximately 11-fold human exposure at 200 mg twice
daily based on the AUC0-24).
Animal Toxicology
An increase in the incidence of background findings of spermatocele with
or without secondary changes such as epididymal hypospermia as well as minimal
to slight dilation of the seminiferous tubules was seen in the juvenile
rat. These reproductive findings while apparently treatment-related did
not increase in incidence or severity with dose and may indicate an exacerbation
of a spontaneous condition. Similar reproductive findings were not observed
in studies of juvenile or adult dogs or in adult rats treated with celecoxib.
The clinical significance of this observation is unknown.
PATIENT COUNSELING INFORMATION
Patients should be informed of the following information before initiating
therapy with CELEBREX and periodically during the course of ongoing therapy.
Medication Guide
Patients should be informed of the availability of a Medication Guide for
NSAIDs that accompanies each prescription dispensed, and should be instructed
to read the Medication Guide prior to using CELEBREX.
Cardiovascular Effects
Patients should be informed that CELEBREX may cause serious CV side effects
such as MI or stroke, which may result in hospitalization and even death.
Patients should be informed of the the signs and symptoms of chest pain,
shortness of breath, weakness, slurring of speech, and to seek immediate
medical advice if they observe any of these signs or symptoms. (see Warnings
and Precautions).
Patients should be informed that CELEBREX can lead to the onset of new
hypertension or worsening of preexisting hypertension, and that CELEBREX
may impair the response of some antihypertensive agents. Patients should
be instructed on the proper follow up for monitoring of blood pressure.
(see Warnings and Precautions and Drug Interactions).
Gastrointestinal Effects
Patients should be informed that CELEBREX can cause gastrointestinal discomfort
and more serious side effects, such as ulcers and bleeding, which may result
in hospitalization and even death. Patients should be informed of the signs
and symptoms of ulcerations and bleeding, and to seek immediate medical
advice if they observe any signs or symptoms that are indicative of these
disorders, including epigastric pain, dyspepsia, melena, and hematemesis.
(see Warnings and Precautions).
Hepatic Effects
Patients should be informed of the warning signs and symptoms of hepatotoxicity
(e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant
tenderness, and “flu-like” symptoms). Patients should be instructed that
they should stop therapy and seek immediate medical therapy if these signs
and symptoms occur (see Warnings and Precautions, Use in Specific Populations).
Adverse Skin Reactions
Patients should be informed that CELEBREX is a sulfonamide and can cause
serious skin side effects such as exfoliative dermatitis, SJS, and TEN,
which may result in hospitalizations and even death. Although serious skin
reactions may occur without warning, patients should be informed of the
signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity
such as itching, and seek immediate medical advice when observing any indicative
signs or symptoms.
Patients should be advised to stop CELEBREX immediately if they develop
any type of rash and contact their physician as soon as possible.
Patients with prior history of sulfa allergy should not take CELEBREX
(see Warnings and Precautions).
Weight Gain and Edema
Long-term administration of NSAIDs including CELEBREX has resulted in renal
injury. Patients at greatest risk are those taking diuretics, ACE-inhibitors,
angiotensin II antagonists, or with renal or liver dysfunction, heart failure,
and the elderly (see Warnings and Precautions, Use in Specific Populations).
Patients should be instructed to promptly report to their physicians
signs or symptoms of unexplained weight gain or edema following treatment
with CELEBREX (see Warnings and Precautions).
Anaphylactoid Reactions
Patients should be informed of the signs and symptoms of an anaphylactoid
reaction (e.g., difficulty breathing, swelling of the face or throat). Patients
should be instructed to seek immediate emergency assistance if they develop
any of these signs and symptoms (see Warnings and Precautions).
Effects During Pregnancy
Patients should be informed that in late pregnancy CELEBREX should be avoided
because it may cause premature closure of the ductus arteriosus (see
Warnings and Precautions, Use in Specific Populations).
Preexisting Asthma
Patients should be instructed to tell their physicians if they have a history
of asthma or aspirin-sensitive asthma because the use of NSAIDs in patients
with aspirin-sensitive asthma has been associated with severe bronchospasm,
which can be fatal. Patients with this form of aspirin sensitivity should
be instructed not to take CELEBREX. Patients with preexisting asthma should
be instructed to seek immediate medical attention if their asthma worsens
after taking CELEBREX (see Warnings and Precautions).
GI Cancer in Familial Adenomatous Polyposis
Patients with FAP should be informed that CELEBREX has not been shown to
reduce colorectal, duodenal or other FAP-related cancers, or the need for
endoscopic surveillance, prophylactic or other FAP-related surgery. Therefore,
all patients with FAP should be instructed to continue their usual care
while receiving CELEBREX (see Warnings and Precautions).