Included as part of the PRECAUTIONS section.
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and
nonselective NSAIDs of up to three years duration have shown an increased risk
of serious cardiovascular (CV) thrombotic events, including myocardial
infarction (MI) and stroke, which can be fatal. Based on available data, it is
unclear that the risk for CV thrombotic events is similar for all NSAIDs. The
relative increase in serious CV thrombotic events over baseline conferred by
NSAID use appears to be similar in those with and without known CV disease or
risk factors for CV disease. However, patients with known CV disease or risk
factors had a higher absolute incidence of excess serious CV thrombotic events,
due to their increased baseline rate. Some observational studies found that
this increased risk of serious CV thrombotic events began as early as the first
weeks of treatment. The increase in CV thrombotic risk has been observed most
consistently at higher doses.
In the APC (Adenoma Prevention with Celecoxib) trial,
there was about a threefold increased risk of the composite endpoint of
cardiovascular death, MI, or stroke for the CELEBREX 400 mg twice daily and CELEBREX
200 mg twice daily treatment arms compared to placebo. The increases in both
celecoxib dose groups versus placebo-treated patients were mainly due to an
increased incidence of myocardial infarction [see Clinical Studies].
A randomized controlled trial entitled the Prospective
Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen
(PRECISION) was conducted to assess the relative cardiovascular thrombotic risk
of a COX-2 inhibitor, celecoxib, compared to the non-selective NSAIDs naproxen
and ibuprofen. Celecoxib 100 mg twice daily was non-inferior to naproxen 375 to
500 mg twice daily and ibuprofen 600 to 800 mg three times daily for the
composite endpoint of the Antiplatelet Trialists' Collaboration (APTC), which
consists of cardiovascular death (including hemorrhagic death), non-fatal
myocardial infarction, and non-fatal stroke [See Clinical Studies].
To minimize the potential risk for an adverse CV event in
NSAID-treated patients, use the lowest effective dose for the shortest duration
possible. Physicians and patients should remain alert for the development of
such events, throughout the entire treatment course, even in the absence of
previous CV symptoms. Patients should be informed about the symptoms of serious
CV events 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 an NSAID, such as celecoxib,
increases the risk of serious gastrointestinal (GI) events [see Gastrointestinal Bleeding, Ulceration, and Perforation].
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a 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. NSAIDs are
contraindicated in the setting of CABG [see CONTRAINDICATIONS].
Observational studies conducted in the Danish National
Registry have demonstrated that patients treated with NSAIDs in the post-MI
period were at increased risk of reinfarction, CV-related death, and all-cause
mortality beginning in the first week of treatment. In this same cohort, the
incidence of death in the first year post-MI was 20 per 100 person years in
NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed
patients. Although the absolute rate of death declined somewhat after the first
year post-MI, the increased relative risk of death in NSAID users persisted
over at least the next four years of follow-up.
Avoid the use of Celebrex in patients with a recent MI
unless the benefits are expected to outweigh the risk of recurrent CV thrombotic
events. If Celebrex is used in patients with a recent MI, monitor patients for
signs of cardiac ischemia.
Gastrointestinal Bleeding, Ulceration, And Perforation
NSAIDs, including celecoxib cause serious
gastrointestinal (GI) adverse events including inflammation, bleeding,
ulceration, and perforation of the esophagus, 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 CELEBREX.
Only one in five patients who develop a serious upper GI adverse event on NSAID
therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused
by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and
in about 2%-4% of patients treated for one year. However, even short-term NSAID
therapy is not without risk.
Risk Factors For GI Bleeding, Ulceration, And Perforation
Patients with a prior history of peptic ulcer disease
and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk
for developing a GI bleed compared to patients without these risk factors.
Other factors that increase the risk of GI bleeding in patients treated with
NSAIDs include longer duration of NSAID therapy; concomitant use of oral
corticosteroids, aspirin, anticoagulants; or selective serotonin reuptake
inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health
status. Most postmarketing reports of fatal GI events occurred in elderly or
debilitated patients. Additionally, patients with advanced liver disease and/or
coagulopathy are at increased risk for GI bleeding.
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].
Strategies To Minimize The GI Risks In NSAID-Treated
- Use the lowest effective dosage for the shortest possible
- Avoid administration of more than one NSAID at a time.
- Avoid use in patients at higher risk unless benefits are
expected to outweigh the increased risk of bleeding. For such patients, as well
as those with active GI bleeding, consider alternate therapies other than
- Remain alert for signs and symptoms of GI ulceration and
bleeding during NSAID therapy.
- If a serious GI adverse event is suspected, promptly
initiate evaluation and treatment, and discontinue CELEBREX until a serious GI
adverse event is ruled out.
- In the setting of concomitant use of low-dose aspirin for
cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding
[see DRUG INTERACTIONS].
Elevations of ALT or AST (three or more times the upper
limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated
patients in clinical trials. In addition, rare, sometimes fatal, cases of
severe hepatic injury, including fulminant hepatitis, liver necrosis, and
hepatic failure have been reported.
Elevations of ALT or AST (less than three times ULN) may
occur in up to 15% of patients treated with NSAIDs including celecoxib.
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.
Inform patients of the warning signs and symptoms of
hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice,
right upper quadrant tenderness, and “flu-like” symptoms). If
clinical signs and symptoms consistent with liver disease develop, or if
systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue CELEBREX
immediately, and perform a clinical evaluation of the patient.
NSAIDs, including CELEBREX, can lead to new onset of
hypertension or worsening of preexisting hypertension, either of which may
contribute to the increased incidence of CV events. Patients taking angiotensin
converting enzyme (ACE) inhibitors, thiazide diuretics or loop diuretics may
have impaired response to these therapies when taking NSAIDs [see DRUG
See Clinical Studies for additional blood pressure
data for CELEBREX.
Monitor blood pressure (BP) during the initiation of
NSAID treatment and throughout the course of therapy.
Heart Failure And Edema
The Coxib and traditional NSAID Trialists' Collaboration
meta-analysis of randomized controlled trials demonstrated an approximately
twofold increase in hospitalizations for heart failure in COX-2
selective-treated patients and nonselective NSAID-treated patients compared to
placebo-treated patients. In a Danish National Registry study of patients with
heart failure, NSAID use increased the risk of MI, hospitalization for heart
failure, and death.
Additionally, fluid retention and edema have been
observed in some patients treated with NSAIDs. Use of celecoxib may blunt the
CV effects of several therapeutic agents used to treat these medical conditions
(e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see
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), ibuprofen 800 mg three times daily and diclofenac 75 mg twice
daily were 4.5%, 6.9% and 4.7%, respectively.
Avoid the use of CELEBREX in patients with severe heart
failure unless the benefits are expected to outweigh the risk of worsening
heart failure. If CELEBREX is used in patients with severe heart failure,
monitor patients for signs of worsening heart failure.
Renal Toxicity And Hyperkalemia
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,
dehydration, hypovolemia, heart failure, liver dysfunction, those taking
diuretics, ACE-inhibitors or the ARBs, and the elderly. Discontinuation of
NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical
studies regarding the use of CELEBREX in patients with advanced renal disease.
The renal effects of CELEBREX may hasten the progression of renal dysfunction
in patients with preexisting renal disease.
Correct volume status in dehydrated or hypovolemic
patients prior to initiating CELEBREX. Monitor renal function in patients with
renal or hepatic impairment, heart failure, dehydration, or hypovolemia during
use of CELEBREX [see DRUG INTERACTIONS]. Avoid the use of CELEBREX in
patients with advanced renal disease unless the benefits are expected to
outweigh the risk of worsening renal function. If CELEBREX is used in patients
with advanced renal disease, monitor patients for signs of worsening renal function.
Increases in serum potassium concentration, including
hyperkalemia, have been reported with use of NSAIDs, even in some patients
without renal impairment. In patients with normal renal function, these effects
have been attributed to a hyporeninemic-hypoaldosteronism state.
Celecoxib has been associated with anaphylactic reactions
in patients with and without known hypersensitivity to celecoxib and in
patients with aspirin sensitive asthma. Celebrex is a sulfonamide and both
NSAIDs and sulfonamides may cause allergic type reactions including
anaphylactic symptoms and life-threatening or less severe asthmatic episodes in
certain susceptible people [see CONTRAINDICATIONS and Exacerbation Of Asthma Related To Aspirin Sensitivity].
Seek emergency help if any anaphylactic reaction occurs.
Exacerbation Of Asthma Related To Aspirin Sensitivity
A subpopulation of patients with asthma may have
aspirin-sensitive asthma which may include chronic rhinosinusitis complicated
by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to
aspirin and other NSAIDs. Because cross-reactivity between aspirin and other
NSAIDs has been reported in such aspirin-sensitive patients, CELEBREX is
contraindicated in patients with this form of aspirin sensitivity [see CONTRAINDICATIONS].
When CELEBREX is used in patients with preexisting asthma (without known
aspirin sensitivity), monitor patients for changes in the signs and symptoms of
Serious Skin Reactions
Serious skin reactions have occurred following treatment
with Celebrex, including erythema multiforme, exfoliative dermatitis,
Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction
with eosinophilia and systemic symptoms (DRESS), and acute generalized
exanthematous pustulosis (AGEP). These serious events may occur without warning
and can be fatal.
Inform patients about the signs and symptoms of serious
skin reactions, and to discontinue the use of CELEBREX at the first appearance
of skin rash or any other sign of hypersensitivity. CELEBREX is contraindicated
in patients with previous serious skin reactions to NSAIDs [see CONTRAINDICATIONS].
Premature Closure Of Fetal Ductus Arteriosus
Celecoxib may cause premature closure of the ductus
arteriosus. Avoid use of NSAIDs, including CELEBREX, in pregnant women starting
at 30 weeks of gestation (third trimester) [see Use In Specific Populations].
Anemia has occurred in NSAID-treated patients. This may
be due to occult or gross blood loss, fluid retention, or an incompletely
described effect on erythropoiesis. If a patient treated with CELEBREX has any signs
or symptoms of anemia, monitor hemoglobin or hematocrit.
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.
NSAIDs, including CELEBREX, may increase the risk of
bleeding events. Co-morbid conditions such as coagulation disorders or
concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g.,
aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine
reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for
signs of bleeding [see DRUG INTERACTIONS].
Masking Of Inflammation And Fever
The pharmacological activity of CELEBREX in reducing
inflammation, and possibly fever, may diminish the utility of diagnostic signs
in detecting infections.
Because serious GI bleeding, hepatotoxicity, and renal
injury can occur without warning symptoms or signs, consider monitoring
patients on long-term NSAID treatment with a CBC and a chemistry profile
periodically [see WARNINGS AND PRECAUTIONS].
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
Disseminated Intravascular Coagulation (DIC)
Because of the risk of disseminated intravascular
coagulation with use of CELEBREX in pediatric patients with systemic onset JRA,
monitor patients for signs and symptoms of abnormal clotting or bleeding, and
inform patients and their caregivers to report symptoms as soon as possible.
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide) that accompanies each
prescription dispensed. Inform patients, families, or their caregivers of the
following information before initiating therapy with CELEBREX and periodically
during the course of ongoing therapy.
Advise patients to be alert for
the symptoms of cardiovascular thrombotic events, including chest pain,
shortness of breath, weakness, or slurring of speech, and to report any of
these symptoms to their health care provider immediately [see WARNINGS AND
Ulceration, And Perforation
Advise patients to report
symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia,
melena, and hematemesis to their health care provider. In the setting of
concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of
the increased risk for and the signs and symptoms of GI bleeding [see WARNINGS
Inform patients of the warning
signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy,
pruritus, diarrhea jaundice, right upper quadrant tenderness, and “flu-like”
symptoms). If these occur, instruct patients to stop CELEBREX and seek
immediate medical therapy [see WARNINGS AND PRECAUTIONS, Use In Specific
Heart Failure And Edema
Advise patients to be alert for the symptoms of
congestive heart failure including shortness of breath, unexplained weight
gain, or edema and to contact their healthcare provider if such symptoms occur
[see WARNINGS AND PRECAUTIONS].
Inform patients of the signs of an anaphylactic reaction
(e.g., difficulty breathing, swelling of the face or throat). Instruct patients
to seek immediate emergency help if these occur [see CONTRAINDICATIONS and
WARNINGS AND PRECAUTIONS].
Serious Skin Reactions
Advise patients to stop CELEBREX immediately if they
develop any type of rash and to contact their healthcare provider as soon as
possible [see WARNINGS AND PRECAUTIONS].
Advise females of reproductive potential who desire
pregnancy that NSAIDs, including CELEBREX, may be associated with a reversible
delay in ovulation [see Use In Specific Populations].
Inform pregnant women to avoid use of CELEBREX and other
NSAIDs starting at 30 weeks of gestation because of the risk of the premature
closing of the fetal ductus arteriosus [see WARNINGS
AND PRECAUTIONS and Use In Specific Populations].
Avoid Concomitant Use Of NSAIDs
Inform patients that the concomitant use of CELEBREX with
other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended
due to the increased risk of gastrointestinal toxicity, and little or no
increase in efficacy [see WARNINGS AND PRECAUTIONS
and DRUG INTERACTIONS]. Alert patients that NSAIDs may be present in
“over the counter” medications for treatment of colds, fever, or insomnia.
Use Of NSAIDS And Low-Dose Aspirin
Inform patients not to use low-dose aspirin concomitantly
with CELEBREX until they talk to their healthcare provider [see DRUG
Impairment Of Fertility
Celecoxib was not carcinogenic
in Sprague-Dawley rats given oral doses up to 200 mg/kg for males and 10 mg/kg
for females (approximately 2-to 4-times 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.
Impairment Of Fertility
Celecoxib had no effect on male or female fertility or
male reproductive function in rats at oral doses up to 600 mg/kg/day (approximately
11times human exposure at 200 mg twice daily based on the AUC0-24). At
≥50 mg/kg/day (approximately 6-times human exposure based on the AUC0-24 at
200 mg twice daily) there was increased preimplantation loss.
Use In Specific Populations
Pregnancy Category C
Pregnancy category D from 30
weeks of gestation onward.
Use of NSAIDs, including CELEBREX,
during the third trimester of pregnancy increases the risk of premature closure
of the fetal ductus arteriosus. Avoid use of NSAIDs, including CELEBREX, in
pregnant women starting at 30 weeks of gestation.
There are no adequate and
well-controlled studies of CELEBREX in pregnant women. Data from observational
studies regarding potential embryofetal risks of NSAID use in women in the
first or second trimesters of pregnancy are inconclusive. In animal
reproduction studies, embryo-fetal deaths and an increase in diaphragmatic
hernias were observed in rats administered celecoxib daily during the period of
organogenesis at oral doses approximately 6 times the maximum
recommended human dose of 200 mg twice daily. In addition, structural abnormalities
(e.g., septal defects, ribs fused, sternebrae fused and sternebrae misshapen)
were observed in rabbits given daily oral doses of celecoxib during the period
of organogenesis at approximately 2 times the MRHD [see Data]. Based on
animal data, prostaglandins have been shown to have an important role in
endometrial vascular permeability, blastocyst implantation, and
decidualization. In animal studies, administration of prostaglandin synthesis
inhibitors such as celecoxib, resulted in increased pre-and post-implantation
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies have a
background risk of birth defect, loss, or other adverse outcomes. In the
general U.S. population, all clinically recognized pregnancies, regardless of
drug exposure, have a background rate of 2-4% for major malformations, and
15-20% for pregnancy loss.
Labor Or Delivery
There are no studies on the effects of CELEBREX during
labor or delivery. In animal studies, NSAIDs, including celecoxib, inhibit
prostaglandin synthesis, cause delayed parturition, and increase the incidence
The available data do not establish the presence or
absence of developmental toxicity related to the use of Celebrex.
Celecoxib at oral doses ≥150 mg/kg/day
(approximately 2 times the 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 times human
exposure based on the AUC0-24 at 200 mg twice daily for RA) throughout
organogenesis. In rats, exposure to celecoxib during early embryonic
development resulted in pre-implantation and post-implantation losses at oral
doses ≥50 mg/kg/day (approximately 6 times human exposure based on the
AUC0-24 at 200 mg twice daily for RA).
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 twice daily). The effects of CELEBREX
on labor and delivery in pregnant women are unknown.
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.
The developmental and health benefits of breastfeeding should be considered
along with the mother's clinical need for CELEBREX and any potential adverse
effects on the breastfed infant from the CELEBREX or from the underlying
Females And Males Of Reproductive Potential
Based on the mechanism of action, the use of
prostaglandin-mediated NSAIDs, including CELEBREX, may delay or prevent rupture
of ovarian follicles, which has been associated with reversible infertility in
some women. Published animal studies have shown that administration of
prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin
mediated follicular rupture required for ovulation. Small studies in women
treated with NSAIDs have also shown a reversible delay in ovulation. Consider
withdrawal of NSAIDs, including CELEBREX, in women who have difficulties
conceiving or who are undergoing investigation of infertility.
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). When NSAIDs
including celecoxib are used in patients with systemic onset JRA, monitor
patients for signs and symptoms of abnormal clotting or bleeding, 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
Alternative therapies for treatment of JRA should be
considered in pediatric patients identified to be CYP2C9 poor metabolizers [see
Poor Metabolizers of CYP2C9 substrates].
Elderly patients, compared to younger patients, are at
greater risk for NSAID-associated serious cardiovascular, gastrointestinal,
and/or renal adverse reactions. If the anticipated benefit for the elderly
patient outweighs these potential risks, start dosing at the low end of the
dosing range, and monitor patients for adverse effects [see WARNINGS AND PRECAUTIONS].
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].
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
CELEBREX is not recommended in patients with severe renal
insufficiency [see WARNINGS AND PRECAUTIONS
and CLINICAL PHARMACOLOGY].
Poor Metabolizers Of CYP2C9 Substrates
In patients who are known or suspected to be poor CYP2C9
metabolizers (i.e., CYP2C9*3/*3), based on genotype or previous
history/experience with other CYP2C9 substrates (such as warfarin, phenytoin)
administer CELEBREX starting with 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