Carefully consider the potential benefits and risks of Celebrex (Celecoxib) and other treatment options before deciding to use Celebrex (Celecoxib) . Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals []

Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient.

These doses can be given without regard to timing of meals.

Capsules: 50 mg, 100 mg, 200 mg and 400 mg

Celebrex (Celecoxib) is contraindicated:

Chronic use of Celebrex (Celecoxib) 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 (Celecoxib) 400 mg twice daily and 2.8 (95% CI 1.1 – 7.2) with Celebrex (Celecoxib) 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 [].

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 (Celecoxib) , 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 (Celecoxib) does increase the risk of serious GI events [].

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 [].

Risk of GI Ulceration, Bleeding, and Perforation
NSAIDs, including Celebrex (Celecoxib) , 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 []. 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 (Celecoxib) 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.

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 (Celecoxib) []. In controlled clinical trials of Celebrex (Celecoxib) , 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 (Celecoxib) and 5% for placebo, and approximately 0.2% of patients taking Celebrex (Celecoxib) 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 (Celecoxib) . If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Celebrex (Celecoxib) should be discontinued.

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 (Celecoxib) have shown renal effects similar to those observed with comparator NSAIDs.

No information is available from controlled clinical studies regarding the use of Celebrex (Celecoxib) in patients with advanced renal disease. Therefore, treatment with Celebrex (Celecoxib) is not recommended in these patients with advanced renal disease. If Celebrex (Celecoxib) therapy must be initiated, close monitoring of the patient's renal function is advisable.

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 (Celecoxib) should be discontinued.

In controlled clinical trials, elevated BUN occurred more frequently in patients receiving Celebrex (Celecoxib) 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.

Of the Celebrex (Celecoxib) -treated patients in the pre-marketing 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 received a total daily dose of Celebrex (Celecoxib) of 200 mg (100 mg twice daily or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg twice daily). Approximately 3,900 patients received Celebrex (Celecoxib) 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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Celebrex (Celecoxib) 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 (Celecoxib) has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex (Celecoxib) or other COX-2 selective and non-selective NSAIDs [].

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 ].

Alternative therapies for treatment of JRA should be considered in pediatric patients identified to be CYP2C9 poor metabolizers [see ].

No overdoses of Celebrex (Celecoxib) 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.

Celebrex (Celecoxib) is chemically designated as 4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. The empirical formula is CHFNOS, and the molecular weight is 381.38; the chemical structure is as follows:

Celebrex (Celecoxib) oral capsules contain either 50 mg, 100 mg, 200 mg or 400 mg of celecoxib, together with inactive ingredients including: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate.

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 AUC 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 AUC 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 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 AUC).

Celebrex (Celecoxib) has demonstrated significant reduction in joint tenderness/pain and joint swelling compared to placebo. Celebrex (Celecoxib) 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 (Celecoxib) 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 (Celecoxib) doses of 100 mg twice daily and 200 mg twice daily were similar in effectiveness and both were comparable to naproxen 500 mg twice daily.

Although Celebrex (Celecoxib) 100 mg twice daily and 200 mg twice daily provided similar overall effectiveness, some patients derived additional benefit from the 200 mg twice daily dose. Doses of 400 mg twice daily provided no additional benefit above that seen with 100–200 mg twice daily.

In a 12-week, randomized, double-blind active-controlled, parallel-group, multicenter, non-inferiority study, patients from 2 years to 17 years of age with pauciarticular, polyarticular course JRA or systemic onset JRA (with currently inactive systemic features), received one of the following treatments: celecoxib 3 mg/kg (to a maximum of 150 mg) twice daily; celecoxib 6 mg/kg (to a maximum of 300 mg) twice daily; or naproxen 7.5 mg/kg (to a maximum of 500 mg) twice daily. The response rates were based upon the JRA Definition of Improvement greater than or equal to 30% (JRA DOI 30) criterion, which is a composite of clinical, laboratory, and functional measures of JRA. The JRA DOI 30 response rates at week 12 were 69%, 80% and 67% in the celecoxib 3 mg/kg BID, celecoxib 6 mg/kg BID, and naproxen 7.5 mg/kg BID treatment groups, respectively.

The efficacy and safety of Celebrex (Celecoxib) for JRA have not been studied beyond six months. The long-term cardiovascular toxicity in children exposed to Celebrex (Celecoxib) has not been evaluated and it is unknown if the long-term risk may be similar to that seen in adults exposed to Celebrex (Celecoxib) or other COX-2 selective and non-selective NSAIDs [(].

Celebrex (Celecoxib) 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 (Celecoxib) 400 mg twice daily, 12% for Celebrex (Celecoxib) 100 mg twice daily and 5% for placebo. The reduction in polyps observed with Celebrex (Celecoxib) 400 mg twice daily was statistically superior to placebo at the six-month timepoint (p=0.003). (See Figure 1)

Celebrex (Celecoxib) 50 mg capsules are white, with reverse printed white on red band of body and cap with markings of 7767 on the cap and 50 on the body, supplied as:

0025-1515-01                 bottle of 60

Celebrex (Celecoxib) 100 mg capsules are white, with reverse printed white on blue band of body and cap with markings of 7767 on the cap and 100 on the body, supplied as:

0025-1520-31                 bottle of 100

0025-1520-51                 bottle of 500

0025-1520-34                 carton of 100 unit dose

Celebrex (Celecoxib) 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:

0025-1525-31                 bottle of 100

0025-1525-51                 bottle of 500

0025-1525-34                 carton of 100 unit dose

Celebrex (Celecoxib) 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:

0025-1530-02                 bottle of 60

0025-1530-01                 carton of 100 unit dose

Patients should be informed of the following information before initiating therapy with Celebrex (Celecoxib) and periodically during the course of ongoing therapy.

Patients should be informed that Celebrex (Celecoxib) 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. [].

Patients should be informed that Celebrex (Celecoxib) can lead to the onset of new hypertension or worsening of preexisting hypertension, and that Celebrex (Celecoxib) may impair the response of some antihypertensive agents. Patients should be instructed on the proper follow up for monitoring of blood pressure. [].

Patients should be informed that Celebrex (Celecoxib) 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 (Celecoxib) 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 (Celecoxib) [].

Long-term administration of NSAIDs including Celebrex (Celecoxib) 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 [].

Patients should be instructed to promptly report to their physicians signs or symptoms of unexplained weight gain or edema following treatment with Celebrex (Celecoxib) [].

Celebrex (Celecoxib)

(celecoxib)

100 mg

10 Capsules

Celebrex (Celecoxib)

(celecoxib)

200 mg

10 Capsules