09009f2a804748931.doc

CELEBREX®
Cardiovascular Risk
• CELEBREX may cause an increased risk of serious cardiovascular thrombotic events,
myocardial infarction, and stroke, which can be fatal. All NSAIDs may have a similar
risk. This risk may increase with duration of use. Patients with cardiovascular disease
or risk factors for cardiovascular disease may be at greater risk (see WARNINGS and
CLINICAL TRIALS).
• CELEBREX is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Gastrointestinal Risk
• NSAIDs, including CELEBREX, cause an increased risk of serious gastrointestinal
adverse events including bleeding, ulceration, and perforation of the stomach or
intestines, which can be fatal. These events can occur at any time during use and
without warning symptoms. Elderly patients are at greater risk for serious
gastrointestinal events (see WARNINGS).
DESCRIPTION
CELEBREX (celecoxib) is chemically designated as 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. It has the following chemical structure: The empirical formula for celecoxib is C H F N O S, and the molecular weight is 381.38. CELEBREX oral capsules contain either 100 mg, 200 mg or 400 mg of celecoxib. The inactive ingredients in CELEBREX capsules include: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone, sodium lauryl sulfate and titanium dioxide. CLINICAL PHARMACOLOGY
Mechanism of Action: CELEBREX is a nonsteroidal anti-inflammatory drug that exhibits anti-
inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of
CELEBREX is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of
cyclooxygenase-2 (COX-2), and at therapeutic concentrations in humans, CELEBREX does not
inhibit the cyclooxygenase-1 (COX-1) isoenzyme. In animal colon tumor models, celecoxib
reduced the incidence and multiplicity of tumors.
Platelets
In clinical trials using normal volunteers, CELEBREX at single doses up to 800 mg and multiple
doses of 600 mg twice daily for up to 7 days duration (higher than recommended therapeutic
doses) had no effect on reduction of platelet aggregation or increase in bleeding time. Because
of its lack of platelet effects, CELEBREX is not a substitute for aspirin for cardiovascular
prophylaxis. It is not known if there are any effects of CELEBREX on platelets that may
contribute to the increased risk of serious cardiovascular thrombotic adverse events associated
with the use of CELEBREX.
Fluid Retention
Inhibition of PGE2 synthesis may lead to sodium and water retention through increased
reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments
of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by
counteracting the action of antidiuretic hormone.

Pharmacokinetics:
Absorption
Peak plasma levels of celecoxib occur approximately 3 hrs after an oral dose. Under fasting
conditions, both peak plasma levels (Cmax) and area under the curve (AUC) are roughly dose
proportional up to 200 mg BID; at higher doses there are less than proportional increases in
Cmax and AUC (see Food Effects). Absolute bioavailability studies have not been conducted.
With multiple dosing, steady state conditions are reached on or before Day 5.
The pharmacokinetic parameters of celecoxib in a group of healthy subjects are shown Summary of Single Dose (200 mg) Disposition
Kinetics of Celecoxib in Healthy Subjects1
Cmax, ng/mL
Tmax, hr
Effective t1/2, hr
Vss/F, L
CL/F, L/hr
1Subjects under fasting conditions (n=36, 19-52 yrs.)
Food Effects
When CELEBREX capsules were taken with a high fat meal, peak plasma levels were delayed for
about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Under fasting
conditions, at doses above 200 mg, there is less than a proportional increase in Cmax and AUC,
which is thought to be due to the low solubility of the drug in aqueous media. Coadministration
of CELEBREX with an aluminum- and magnesium-containing antacid resulted in a reduction in
plasma celecoxib concentrations with a decrease of 37% in Cmax and 10% in AUC. CELEBREX,
at doses up to 200 mg BID can be administered without regard to timing of meals. Higher doses
(400 mg BID) should be administered with food to improve absorption.
Distribution
In healthy subjects, celecoxib is highly protein bound (~97%) within the clinical dose range. In
vitro studies indicate that celecoxib binds primarily to albumin and, to a lesser extent, α1-acid
glycoprotein. The apparent volume of distribution at steady state (Vss/F) is approximately 400
L, suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red
blood cells.
Metabolism
Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a
primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been
identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.
Patients who are known or suspected to be P450 2C9 poor metabolizers based on a previous
history should be administered celecoxib with caution as they may have abnormally high plasma
levels due to reduced metabolic clearance.
Excretion
Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug
recovered in the urine and feces. Following a single oral dose of radiolabeled drug,
approximately 57% of the dose was excreted in the feces and 27% was excreted into the urine.
The primary metabolite in both urine and feces was the carboxylic acid metabolite (73% of
dose) with low amounts of the glucuronide also appearing in the urine. It appears that the low
solubility of the drug prolongs the absorption process making terminal half-life (t1/2)
determinations more variable. The effective half-life is approximately 11 hours under fasted
conditions. The apparent plasma clearance (CL/F) is about 500 mL/min.
Special Populations

Geriatric: At steady state, elderly subjects (over 65 years old) had a 40% higher Cmax and a
50% higher AUC compared to the young subjects. In elderly females, celecoxib Cmax and
AUC are higher than those for elderly males, but these increases are predominantly due to
lower body weight in elderly females. Dose adjustment in the elderly is not generally necessary.
However, for patients of less than 50 kg in body weight, initiate therapy at the lowest
recommended dose.

Pediatric: CELEBREX capsules have not been investigated in pediatric patients below 18 years
of age.
Race: Meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher
AUC of celecoxib in Blacks compared to Caucasians. The cause and clinical significance of
this finding is unknown.
Hepatic Insufficiency: A pharmacokinetic study in subjects with mild (Child-Pugh Class A)
and moderate (Child-Pugh Class B) hepatic impairment has shown that steady-state celecoxib
AUC is increased about 40% and 180%, respectively, above that seen in healthy control
subjects. Therefore, the daily recommended dose of CELEBREX capsules should be reduced by
approximately 50% in patients with moderate (Child-Pugh Class B) hepatic impairment.
Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied. The use of
CELEBREX in patients with severe hepatic impairment is not recommended (see DOSAGE
AND ADMINISTRATION).
Renal Insufficiency: In a cross-study comparison, celecoxib AUC was approximately 40%
lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects
with normal renal function. No significant relationship was found between GFR and celecoxib
clearance. Patients with severe renal insufficiency have not been studied. Similar to other
NSAIDs, CELEBREX is not recommended in patients with severe renal insufficiency (see
WARNINGS – Advanced Renal Disease).

Drug Interactions
Also see PRECAUTIONS – Drug Interactions.
General: Significant interactions may occur when celecoxib is administered together with drugs
that inhibit P450 2C9. In vitro studies indicate that celecoxib is not an inhibitor of cytochrome
P450 2C9, 2C19 or 3A4.
Clinical studies with celecoxib have identified potentially significant interactions with
fluconazole and lithium. Experience with nonsteroidal anti-inflammatory drugs (NSAIDs)
suggests the potential for interactions with furosemide and ACE inhibitors. The effects of
celecoxib on the pharmacokinetics and/or pharmacodynamics of glyburide, ketoconazole,
methotrexate, phenytoin, and tolbutamide have been studied in vivo and clinically important interactions have not been found. CLINICAL STUDIES
Osteoarthritis (OA): CELEBREX has demonstrated significant reduction in joint pain
compared to placebo. CELEBREX was evaluated for treatment of the signs and the symptoms of
OA of the knee and hip in placebo- and active-controlled clinical trials of up to 12 weeks
duration. In patients with OA, treatment with CELEBREX 100 mg BID or 200 mg QD resulted
in improvement in WOMAC (Western Ontario and McMaster Universities) osteoarthritis index,
a composite of pain, stiffness, and functional measures in OA. In three 12-week studies of pain
accompanying OA flare, CELEBREX doses of 100 mg BID and 200 mg BID provided significant
reduction of pain within 24-48 hours of initiation of dosing. At doses of 100 mg BID or 200 mg
BID the effectiveness of CELEBREX was shown to be similar to that of naproxen 500 mg BID.
Doses of 200 mg BID provided no additional benefit above that seen with 100 mg BID. A
total daily dose of 200 mg has been shown to be equally effective whether administered as 100
mg BID or 200 mg QD.
Rheumatoid Arthritis (RA): CELEBREX has demonstrated significant reduction in joint
tenderness/pain and joint swelling compared to placebo. CELEBREX was evaluated for
treatment of the signs and symptoms of RA in placebo- and active-controlled clinical trials of up
to 24 weeks in duration. CELEBREX was shown to be superior to placebo in these studies,
using the ACR20 Responder Index, a composite of clinical, laboratory, and functional measures
in RA. CELEBREX doses of 100 mg BID and 200 mg BID were similar in effectiveness and
both were comparable to naproxen 500 mg BID.
Although CELEBREX 100 mg BID and 200 mg BID provided similar overall effectiveness, some patients derived additional benefit from the 200 mg BID dose. Doses of
400 mg BID provided no additional benefit above that seen with 100-200 mg BID.
Analgesia, including primary dysmenorrhea: In acute analgesic models of post-oral surgery
pain, post-orthopedic surgical pain, and primary dysmenorrhea, CELEBREX relieved pain that
was rated by patients as moderate to severe. Single doses (see DOSAGE AND
ADMINISTRATION) of CELEBREX provided pain relief within 60 minutes.
Ankylosing Spondylitis (AS): CELEBREX was evaluated in AS patients in two placebo- and
active-controlled clinical trials of 6 and 12 weeks duration. CELEBREX at doses of
100 mg BID, 200 mg QD and 400 mg QD was shown to be statistically superior to placebo in
these studies for all three co-primary efficacy measures assessing global pain intensity (Visual
Analogue Scale), global disease activity (Visual Analogue Scale) and functional impairment
(Bath Ankylosing Spondylitis Functional Index). In the 12-week study, there was no difference
in the extent of improvement between the 200 mg and 400 mg celecoxib doses in a comparison
of mean change from baseline, but there was a greater percentage of patients who responded to
celecoxib 400 mg, 53%, than to celecoxib 200 mg, 44%, using the Assessment in Ankylosing
Spondylitis response criteria (ASAS 20).1 The ASAS 20 defines a responder as improvement
from baseline of at least 20% and an absolute improvement of at least 10 mm, on a 0 to 100
mm scale, in at least three of the four following domains: patient global, pain, Bath Ankylosing
Spondylitis Functional Index, and inflammation. The responder analysis also demonstrated no
change in the responder rates beyond 6 weeks.
Familial Adenomatous Polyposis (FAP): CELEBREX was evaluated to reduce the number of
adenomatous colorectal polyps. A randomized double-blind placebo-controlled study was
conducted in patients with FAP. The study population included 58 patients with a prior subtotal
or total colectomy and 25 patients with an intact colon. Thirteen patients had the attenuated
FAP phenotype.
One area in the rectum and up to four areas in the colon were identified at baseline for specific follow-up, and polyps were counted at baseline and following six months of treatment. The mean reduction in the number of colorectal polyps was 28% for CELEBREX 400 mg BID, 12% for CELEBREX 100 mg BID and 5% for placebo. The reduction in polyps observed with CELEBREX 400 mg BID was statistically superior to placebo at the six-month timepoint (p=0.003). (See Figure 1.) Percent Change from Baseline in
Number of Colorectal Polyps
(FAP Patients)
100 mg BID
400 mg BID*
Percent Change from Baseline
* p=0.003 versus placebo
Special Studies
Celecoxib Long-Term Arthritis Safety Study (CLASS)
The Celecoxib Long-Term Arthritis Safety Study (CLASS) was a prospective long-term safety
outcome study conducted postmarketing in approximately 5,800 OA patients and 2,200 RA
patients. Patients received CELEBREX 400 mg BID (4-fold and 2-fold the recommended OA
and RA doses, respectively, and the approved dose for FAP), ibuprofen 800 mg TID or
diclofenac 75 mg BID (common therapeutic doses). Median exposures for CELEBREX (n =
3,987) and diclofenac (n = 1,996) were 9 months while ibuprofen (n = 1,985) was 6 months.
The primary endpoint of this outcome study was the incidence of complicated ulcers
(gastrointestinal bleeding, perforation or obstruction). Patients were allowed to take
concomitant low-dose (≤ 325 mg/day) aspirin (ASA) for cardiovascular prophylaxis (ASA
subgroups: CELEBREX, n = 882; diclofenac, n = 445; ibuprofen, n = 412). Differences in the
incidence of complicated ulcers between CELEBREX and the combined group of ibuprofen and
diclofenac were not statistically significant.
Those patients on CELEBREX and concomitant low-dose ASA (N=882) experienced 4-fold
higher rates of complicated ulcers compared to those not on ASA (N=3105). The Kaplan
Meier rate for complicated ulcers at 9 months was 1.12% versus 0.32% for those on low dose
ASA and those not on ASA, respectively (see WARNINGS — Gastrointestinal (GI)
Effects).
The estimated cumulative rates at 9 months of complicated and symptomatic ulcers for
patients treated with CELEBREX 400 mg BID are described in Table 2. Table 2 also displays
results for patients less than or greater than 65 years of age. The difference in rates between
CELEBREX alone and CELEBREX with ASA groups may be due to the higher risk for GI events
in ASA users.
Complicated and Symptomatic Ulcer Rates in Patients Taking CELEBREX 400 mg BID (Kaplan-Meier
Rates at 9 months [%]) Based on Risk Factors
Complicated and Symptomatic
Ulcer Rates

In a small number of patients with a history of ulcer disease, the complicated and symptomatic
ulcer rates in patients taking CELEBREX alone or CELEBREX with ASA were, respectively,
2.56% (n=243) and 6.85% (n=91) at 48 weeks. These results are to be expected in patients
with a prior history of ulcer disease (see WARNINGS – Gastrointestinal (GI) Effects –
Risk of GI Ulceration, Bleeding, and Perforation and ADVERSE REACTIONS –
Safety Data from CLASS Study – Hematological Events).

Cardiovascular safety outcomes were also evaluated in the CLASS trial. Kaplan-Meier
cumulative rates for investigator-reported serious cardiovascular thromboembolic adverse
events (including MI, pulmonary embolism, deep venous thrombosis, unstable angina, transient
ischemic attacks, and ischemic cerebrovascular accidents) demonstrated no differences
between the CELEBREX, diclofenac, or ibuprofen treatment groups. The cumulative rates in all
patients at nine months for CELEBREX, diclofenac, and ibuprofen were 1.2%, 1.4%, and 1.1%,
respectively. The cumulative rates in non-ASA users at nine months in each of the three
treatment groups were less than 1%. The cumulative rates for myocardial infarction in non-
ASA users at nine months in each of the three treatment groups were less than 0.2%. There
was no placebo group in the CLASS trial, which limits the ability to determine whether the three
drugs tested had no increased risk of CV events or if they all increased the risk to a similar
degree.

Adenomatous Polyp Prevention Studies
Cardiovascular safety was evaluated in two randomized, double-blind, placebo-controlled,
three-year studies involving patients with Sporadic Adenomatous Polyps treated with
CELEBREX. The first of these studies was the APC (Prevention of Sporadic Colorectal
Adenomas with Celecoxib) study, which compared CELEBREX 400 mg twice daily (N=671)
and CELEBREX 200 mg twice daily (N=685) to placebo (N=679). Preliminary safety
information from this trial demonstrated a dose-related increase in serious cardiovascular events
(mainly myocardial infarction [MI]) at CELEBREX doses of 200 mg and 400 mg twice daily
compared to placebo). The cumulative rates of serious cardiovascular thrombotic events began
to differ between the CELEBREX treatment groups and placebo after approximately one year of
treatment. There were 2.8 to 3.1 years of follow-up in the APC trial except those patients who
died earlier. The relative risk (RR) for the composite endpoint of 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.
The second long-term study, PreSAP (Prevention of Colorectal Sporadic Adenomatous
Polyps) compared CELEBREX 400 mg once daily to placebo. Preliminary safety information
from this trial demonstrated no increased cardiovascular risk for the composite endpoint of
cardiovascular death, MI or stroke. The reason for the differing results for CV events in the
APC and PreSAP trials is not known.
Clinical trials of other COX-2 selective and nonselective NSAIDs of up to three-years duration
have shown an increased risk of serious cardiovascular thrombotic events, myocardial
infarction, and stroke, which can be fatal. As a result, all NSAIDs are considered potentially
associated with this risk.
Endoscopic Studies
The correlation between findings of short-term endoscopic studies with CELEBREX and the
relative incidence of clinically significant serious upper GI events with long-term use has not
been established.
A randomized, double-blind study in 430 RA patients was conducted in which an endoscopic
examination was performed at 6 months. The incidence of endoscopic ulcers in patients taking
CELEBREX 200 mg twice daily was 4% vs. 15% for patients taking diclofenac SR 75 mg twice
daily. However, CELEBREX was not statistically different than diclofenac for clinically relevant
GI outcomes in the CLASS trial (see Special Studies - CLASS).

The incidence of endoscopic ulcers was studied in two 12-week, placebo-controlled studies in
2157 OA and RA patients in whom baseline endoscopies revealed no ulcers. There was no
dose relationship for the incidence of gastroduodenal ulcers and the dose of CELEBREX (50 mg
to 400 mg twice daily). The incidence for naproxen 500 mg twice daily was 16.2 and 17.6% in
the two studies, for placebo was 2.0 and 2.3%, and for all doses of CELEBREX the incidence
ranged between 2.7%-5.9%. There have been no large, clinical outcome studies to compare
clinically relevant GI outcomes with CELEBREX and naproxen.
In the endoscopic studies, approximately 11% of patients were taking aspirin (≤ 325 mg/day).
In the CELEBREX groups, the endoscopic ulcer rate appeared to be higher in aspirin users than in non-users. However, the increased rate of ulcers in these aspirin users was less than the endoscopic ulcer rates observed in the active comparator groups, with or without aspirin. Serious clinically significant upper GI bleeding has been observed in patients receiving CELEBREX in controlled and open-labeled trials (see Special Studies - CLASS and
WARNINGS – Gastrointestinal (GI) Effects).
INDICATIONS AND USAGE
Carefully consider the potential benefits and risks of CELEBREX and other treatment options
before deciding to use CELEBREX. Use the lowest effective dose for the shortest duration
consistent with individual patient treatment goals (see WARNINGS).
CELEBREX is indicated:
1) For relief of the signs and symptoms of osteoarthritis.
2) For relief of the signs and symptoms of rheumatoid arthritis in adults.
3) For the relief of signs and symptoms of ankylosing spondylitis.
4) For the management of acute pain in adults (see CLINICAL STUDIES).
5) For the treatment of primary dysmenorrhea.
6) To reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis
(FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery). It is not known
whether there is a clinical benefit from a reduction in the number of colorectal polyps in FAP
patients. It is also not known whether the effects of CELEBREX treatment will persist after
CELEBREX is discontinued. The efficacy and safety of CELEBREX treatment in patients with FAP
beyond six months have not been studied (see CLINICAL STUDIES, WARNINGS and
PRECAUTIONS sections).
CONTRAINDICATIONS
CELEBREX is contraindicated in patients with known hypersensitivity to celecoxib. CELEBREX should not be given to patients who have demonstrated allergic-type CELEBREX should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic- like reactions to NSAIDs have been reported in such patients (see WARNINGS —
Anaphylactoid Reactions , and PRECAUTIONS — Preexisting Asthma).
CELEBREX is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS)

WARNINGS
Cardiovascular Effects
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 trial, the
relative risk 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 2.5 (95% CI 1.0 – 6.4) for the CELEBREX
200 mg twice daily compared to placebo (see Special Studies – Adenomatous Polyp
Studies).
All NSAIDs, both COX-2 selective and nonselective, 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 possible. 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 GI WARNINGS).
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
pre-existing 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 Special Studies - CLASS).
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 Special Studies –
CLASS), 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 Special Studies - CLASS). 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 possible duration. 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.
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 and ACE inhibitors, 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.
Advanced Renal Disease
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 and PRECAUTIONS — Preexisting Asthma). 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 CELEBREX should be avoided because it may cause premature closure of the
ductus arteriosus (see PRECAUTIONS – Pregnancy).
Familial Adenomatous Polyposis (FAP): 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.

PRECAUTIONS
General: 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.
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.
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 – post-marketing experience). 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.

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—Platelets).

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.

Information for Patients
Patients should be informed of the following information before initiating therapy with CELEBREX
and periodically during the course of ongoing therapy. Patients should also be encouraged to
read the NSAID Medication Guide that accompanies each prescription dispensed.
1. CELEBREX, like other NSAIDs, may cause serious CV side effects such as MI or stroke, which may result in hospitalization and even death. Although serious CV events
can occur without warning symptoms, patients should be alert for the signs and
symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should
ask for medical advice if they observe any of these signs or symptoms. Patients should
be apprised of the importance of this follow-up (see WARNINGS - Cardiovascular
Effects).
2. CELEBREX, like other NSAIDs, can cause gastrointestinal discomfort and, rarely, more serious side effects, such as ulcers and bleeding, which may result in hospitalization and
even death. Although serious GI tract ulcerations and bleeding can occur without
warning symptoms, patients should be alert for the signs and symptoms of ulcerations
and bleeding, and should ask for medical advice when they observe any signs or
symptoms that are indicative of these disorders, including epigastric pain, dyspepsia,
melena, and hematemesis. Patients should be apprised of the importance of this follow-
up (see WARNINGS — Gastrointestinal (GI) Effects – Risk of Gastrointestinal
Ulceration, Bleeding, and Perforation).
3. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible. CELEBREX is a sulfonamide and can cause serious skin side effects such as exfoliative dermatitis, SJS, and TENS, which may result in hospitalizations and even death. These reactions can occur with all NSAIDs, even non-sulfonamides. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients with prior history of sulfa allergy should not take CELEBREX. 4. Patients should promptly report signs or symptoms of unexplained weight gain or edema 5. 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. 6. 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 – Anaphylactoid Reactions ).
7. Patients should be informed that in late pregnancy CELEBREX should be avoided because it may cause premature closure of the ductus arteriosus. 8. Patients with familial adenomatous polyposis (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.
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.

Drug Interactions
General: Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the
liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done
with caution.
In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of cytochrome P450 2D6. Therefore, there is a potential for an in vivo drug interaction with
drugs that are metabolized by P450 2D6.

ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of
Angiotensin Converting Enzyme (ACE) inhibitors. This interaction should be given
consideration in patients taking CELEBREX concomitantly with ACE-inhibitors.
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 CLINICAL STUDIES — Special Studies — CLASS,
WARNINGS – Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding, and
Perforation, and WARNINGS – Cardiovascular Effects).
Becaus e of its lack of platelet effects, CELEBREX is not a substitute for aspirin for
cardiovascular prophylaxis.

Fluconazole: Concomitant administration of fluconazole at 200 mg QD 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 Pharmacokinetics — Metabolism).
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.

Lithium: In a study conducted in healthy subjects, mean steady-state lithium plasma levels
increased approximately 17% in subjects receiving lithium 450 mg BID with CELEBREX 200 mg
BID as compared to subjects receiving lithium alone. Patients on lithium treatment should be
closely monitored when CELEBREX is introduced or withdrawn.

Methotrexate: In an interaction study of rheumatoid arthritis patients taking methotrexate,
CELEBREX did not have a significant effect on the pharmacokinetics of methotrexate.
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 doses
of 2-5 mg 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.
Carcinogenesis, mutagene sis, 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 BID) 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 BID) 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 BID based on the AUC0-24).
Pregnancy
Teratogenic effects: Pregnancy Category C. Celecoxib at oral doses ≥150 mg/kg/day
(approximately 2-fold human exposure at 200 mg BID 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 BID) 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 BID). 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: Celecoxib is excreted in the milk of lactating rats at concentrations similar
to those in plasma. Limited data from one subject indicate that celecoxib is also excreted in
human milk. Because many drugs are excreted in human milk and because of the potential for
serious adverse reactions in nursing infants from CELEBREX, a decision should be made whether
to discontinue nursing or to discontinue the drug, taking into account the importance of the drug
to the mother.

Pediatric Use
Safety and effectiveness in pediatric patients below the age of 18 years have not been
evaluated.
Geriatric Use
Of the total number of patients who received CELEBREX in 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 – Gastrointestinal (GI) Effects – Risk of GI Ulceration,
Bleeding, and Perforation).
ADVERSE REACTIONS
Of the CELEBREX treated patients in the premarketing controlled clinical trials, approximately
4,250 were patients with OA, approximately 2,100 were patients with RA, and approximately
1,050 were patients with post-surgical pain. More than 8,500 patients have received a total
daily dose of CELEBREX of 200 mg (100 mg BID or 200 mg QD) or more, including more than
400 treated at 800 mg (400 mg BID). Approximately 3,900 patients have received CELEBREX
at these doses for 6 months or more; approximately 2,300 of these have received it for 1 year
or more and 124 of these have received it for 2 years or more.

Adverse events from CELEBREX premarketing controlled arthritis trials: Table 3 lists all
adverse events, regardless of causality, occurring in ≥2% of patients receiving CELEBREX from
12 controlled studies conducted in patients with OA or RA that included a placebo and/or a
positive control group. Since these 12 trials were of different durations, and patients in the trials
may not have been exposed for the same duration of time, these percentages do not capture
cumulative rates of occurrence.
Adverse Events Occurring in ≥2% of CELEBREX Patients
From CELEBREX Premarketing Controlled Arthritis Trials
Naproxen
Diclofenac
Ibuprofen

Gastrointestinal
Abdominal pain

Body as a whole
Back pain

Central and peripheral nervous system
Dizziness

Psychiatric

Respiratory
Pharyngitis
Skin
Rash
In placebo- or active-controlled clinical trials, the discontinuation rate due to adverse events was 7.1% for patients receiving CELEBREX and 6.1% for patients receiving placebo. Among the most common reasons for discontinuation due to adverse events in the CELEBREX treatment groups were dyspepsia and abdominal pain (cited as reasons for discontinuation in 0.8% and 0.7% of CELEBREX patients, respectively). Among patients receiving placebo, 0.6% discontinued due to dyspepsia and 0.6% withdrew due to abdominal pain. The following adverse events occurred in 0.1 - 1.9% of patients regardless of causality.
CELEBREX
(100 - 200 mg BID or 200 mg QD)


Gastrointestinal:
Constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, reflux, hemorrhoids, hiatal hernia, melena, dry mouth, stomatitis, tenesmus, tooth disorder, vomiting Cardiovascular:
Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction General:
Allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral Resistance mechanism
Herpes simplex, herpes zoster, infection bacterial, infection disorders:
fungal, infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis media Central, peripheral
Leg cramps, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, nervous system:
Female reproductive:
Breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual disorder, vaginal
Male reproductive:

Hearing and
vestibular:
Deafness, ear abnormality, earache, tinnitus Heart rate and rhythm:

Liver and biliary
system:
Hepatic function abnormal, SGOT increased, SGPT increased Metabolic and
nutritional:
BUN increased, CPK increased, diabetes mellitus, hypercholesterolemia, hyperglycemia, NPN increase, creatinine increased, alkaline phosphatase increased, weight increase Musculoskeletal:
Arthralgia, arthrosis, bone disorder, fracture accidental, myalgia, neck Platelets (bleeding
or clotting):

Psychiatric:
Anorexia, anxiety, appetite increased, depression, Hemic:

Respiratory:
Bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea,
Skin and appendages:
Alopecia, dermatitis, nail disorder, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, urticaria Application site disorders:
Cellulitis, dermatitis contact, injection site reaction,
Special senses:
Urinary system:
Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus, urinary incontinence, urinary tract infection
Vision:
Blurred vision, cataract, conjunctivitis, eye pain, glaucoma
Other serious adverse reactions which occur rarely (estimated <0.1%), regardless of
causality: The following serious adverse events have occurred rarely in patients taking CELEBREX.
Cases reported only in the post-marketing experience are indicated in italics.
Cardiovascular:
Syncope, congestiv e heart failure, ventricular fibrillation, pulmonary embolism, cerebrovascular accident, peripheral gangrene, thrombophlebitis, vasculitis, deep venous thrombosis
Gastrointestinal:
Intestinal obstruction, intestinal perforation, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, pancreatitis, ileus
Liver and biliary system:
Cholelithiasis, hepatitis, jaundice, liver failure
Hemic and
lymphatic:
Thrombocytopenia, agranulocytosis, aplastic anemia, Metabolic:

Nervous system:
Ataxia, suicide, aseptic meningitis, ageusia, anosmia, fatal intracranial hemorrhage (see PRECAUTIONS – Drug Interactions – Warfarin)
Renal:
Acute renal failure, interstitial nephritis
Skin:
Erythema multiforme, exfoliative dermatitis, Stevens- Johnson syndrome, toxic epidermal necrolysis
General:
Sepsis, sudden death, anaphylactoid reaction, angioedema
Safety Data from CLASS Study:

Hematological Events:
During this study (see Special Studies – CLASS), the incidence of clinically significant
decreases in hemoglobin (>2 g/dL) confirmed by repeat testing was lower in patients on
CELEBREX 400 mg BID (4-fold and 2-fold the recommended OA and RA doses, respectively,
and the approved dose for FAP) compared to patients on either diclofenac 75 mg BID or
ibuprofen 800 mg TID: 0.5%, 1.3% and 1.9%, respectively. The lower incidence of events with
CELEBREX was maintained with or without ASA use (see CLINICAL PHARMACOLOGY -
Platelets).
Withdrawals/Serious Adverse Events:
Kaplan-Meier cumulative rates at 9 months for withdrawals due to adverse events for
CELEBREX, diclofenac and ibuprofen were 24%, 29%, and 26%, respectively. Rates for serious
adverse events (i.e. those causing hospitalization or felt to be life threatening or otherwise
medically significant) regardless of causality were not different across treatment groups,
respectively, 8%, 7%, and 8%.
Adverse events from ankylosing spondylitis studies: A total of 378 patients were treated
with CELEBREX in placebo- and active- controlled ankylosing spondylitis studies. Doses up to
400 mg QD were studied. The types of adverse events reported in the ankylosing spondylitis
studies were similar to those reported in the arthritis studies.
Adverse events from analgesia and dysmenorrhea studies: Approximately 1,700 patients
were treated with CELEBREX in analgesia and dysmenorrhea studies. All patients in post-oral
surgery pain studies received a single dose of study medication. Doses up to 600 mg/day of
CELEBREX were studied in primary dysmenorrhea and post-orthopedic surgery pain studies.
The types of adverse events in the analgesia and dysmenorrhea studies were similar to those
reported in arthritis studies. The only additional adverse event reported was post-dental
extraction alveolar osteitis (dry socket) in the post-oral surgery pain studies.
Adverse events from the controlled trial in familial adenomatous polyposis: The adverse
event profile reported for the 83 patients with familial adenomatous polyposis enrolled in the
randomized, controlled clinical trial was similar to that reported for patients in the arthritis
controlled trials. Intestinal anastomotic ulceration was the only new adverse event reported in
the FAP trial, regardless of causality, and was observed in 3 of 58 patients (one at 100 mg
BID, and two at 400 mg BID) who had prior intestinal surgery.
OVERDOSAGE
No overdoses of CELEBREX were reported during clinical trials. Doses up to 2400 mg/day for
up to 10 days in 12 patients did not result in serious toxicity. Symptoms following acute
NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric
pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur.
Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.
Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may
occur following an overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. No information is available regarding the removal of celecoxib by hemodialysis, but based on its high degree of plasma protein binding (>97%) dialysis is unlikely to be useful in overdose. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. DOSAGE AND ADMINISTRATION
Carefully consider the potential benefits and risks of CELEBREX and other treatment options
before deciding to use CELEBREX. Use the lowest effective dose for the shortest duration
consistent with individual patient treatment goals (see WARNINGS).
For osteoarthritis and rheumatoid arthritis, the lowest dose of CELEBREX should be sought for
each patient. These doses can be given without regard to timing of meals.
Osteoarthritis: For relief of the signs and symptoms of osteoarthritis the recommended oral
dose is 200 mg per day administered as a single dose or as 100 mg twice per day.
Rheumatoid arthritis: For relief of the signs and symptoms of rheumatoid arthritis the
recommended oral dose is 100 to 200 mg twice per day.
Ankylosing Spondylitis (AS): For the management of the signs and symptoms of AS, the
recommended dose of CELEBREX is 200 mg daily single (once per day) or divided (twice per
day) doses. If no effect is observed after 6 weeks, a trial of 400 mg daily may be worthwhile.
If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and
consideration should be given to alternate treatment options.
Management of Acute Pain and Treatment of Primary Dysmenorrhea: The
recommended dose of CELEBREX is 400 mg initially, followed by an additional 200 mg dose if
needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as
needed.
Familial adenomatous polyposis (FAP): Usual medical care for FAP patients should be
continued while on CELEBREX. To reduce the number of adenomatous colorectal polyps in
patients with FAP, the recommended oral dose is 400 mg twice per day to be taken with food.
Special Populations
Hepatic insufficiency: The daily recommended dose of CELEBREX capsules in patients with
moderate hepatic impairment (Child-Pugh Class B) should be reduced by approximately 50%.
The use of CELEBREX in patients with severe hepatic impairment is not recommended (see
CLINICAL PHARMACOLOGY – Special Populations ).
HOW SUPPLIED
CELEBREX 100-mg capsules are white, reverse printed white on blue band of body and cap
with markings of 7767 on the cap and 100 on the body, supplied as:
NDC Number

CELEBREX 200-mg capsules are white, with reverse printed white on gold band with markings
of 7767 on the cap and 200 on the body, supplied as:
NDC Number

CELEBREX 400-mg capsules are white, with reverse printed white on green band with
markings of 7767 on the cap and 400 on the body, supplied as:
NDC Number
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Medication Guide
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a list of prescription NSAID medicines.) What is the most important information I should know about medicines called Non-Steroidal Anti-
Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This
chance increases:
• with longer use of NSAID medicines
NSAID medicines should never be used right before or after a heart surgery called a “coronary artery
bypass graft (CABG)."
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during
treatment. Ulcers and bleeding:

The chance of a person getting an ulcer or bleeding increases with:
• taking medicines called “corticosteroids” and “anticoagulants” NSAID medicines should only be used:
• at the lowest dose possible for your treatment
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical
conditions such as:
• menstrual cramps and other types of short-term pain Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:
• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID • for pain right before or after heart bypass surgery
Tell your healthcare provider:
• about all of your medical conditions. • about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare
provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their
pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Serious side effects include:
Other side effects include:
• heart failure from body swelling (fluid retention) • kidney problems including kidney failure • bleeding and ulcers in the stomach and intestine • liver problems including liver failure • asthma attacks in people who have asthma
Get emergency help right away if you have any of the following symptoms:
• shortness of breath or trouble breathing • weakness in one part or side of your • swelling of the face or throat
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following
symptoms:

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or
pharmacist for more information about NSAID medicines.
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines. • Some of these NSAID medicines are sold in lower doses without a prescription (over –the –counter). Talk to your healthcare provider before using over –the –counter NSAIDs for more than 10 days.
NSAID medicines that need a prescription

Generic Name
Tradename
Cataflam, Voltaren, Arthrotec (combined with misoprostol) Generic Name
Tradename
Motrin, Tab-Profen, Vicoprofen (combined with hydrocodone), Combunox (combined with oxycodone) Indocin, Indocin SR, Indo-Lemmon, Indomethagan Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole) This Medication Guide has been approved by the U.S. Food and Drug Administration.

Source: http://www.drtheo.com/news/documents/Celebrex_PackageInsert.pdf