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CELEBREX(celecoxib)capsule
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use CELEBREX safely and effectively. See full prescribing information for CELEBREX.
CELEBREX ® (celecoxib) capsules
Initial U.S. Approval: 1998
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WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISKS
See full prescribing information for complete boxed warning
Cardiovascular Risk
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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. (5.1,14.7)
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CELEBREX is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. (4, 5.1)
Gastrointestinal Risk
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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 (GI) events. (5.4)
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INDICATIONS AND USAGE
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CELEBREX is a nonsteroidal anti-inflammatory drug indicated for:
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Osteoarthritis (OA) (1.1)
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Rheumatoid Arthritis (RA) (1.2)
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Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older (1.3)
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Ankylosing Spondylitis (AS) (1.4)
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Acute Pain (AP) (1.5)
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Primary Dysmenorrhea (PD) (1.6)
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Familial Adenomatous Polyposis (FAP)-adjunct to usual care) (1.7)
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DOSAGE AND ADMINISTRATION
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Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient. (1, 5.1, 5.4)
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OA: 200 mg once daily or 100 mg twice daily (2.1, 14.1)
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RA: 100 to 200 mg twice daily (2.2, 14.2)
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JRA: 50 mg twice daily in patients 10–25 kg. 100 mg twice daily in patients more than 25 kg (2.3, 14.3)
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AS: 200 mg once daily single dose or 100 mg twice daily. If no effect is observed after 6 weeks, a trial of 400 mg (single or divided doses) may be of benefit (2.4, 14.4)
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AP and PD: 400 mg initially, followed by 200 mg dose if needed on first day. On subsequent days, 200 mg twice daily as needed (2.5, 14.5)
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FAP: 400 mg twice daily with food, as an adjunct to usual care (2.6, 14.6)
Reduce daily dose by 50% in patients with moderate hepatic impairment (Child-Pugh Class B).
Consider a dose reduction by 50% (or alternative management for JRA) in patients who are known or suspected to be CYP2C9 poor metabolizers, (2.7, 8.4, 8.8, 12.3).
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DOSAGE FORMS AND STRENGTHS
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Capsules: 50 mg, 100 mg, 200 mg and 400 mg (3)
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CONTRAINDICATIONS
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Known hypersensitivity to celecoxib or sulfonamides (4)
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History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs (4, 5.7, 5.8, 5.13)
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Use during the perioperative period in the setting of coronary artery bypass graft (CABG) surgery (4, 5.1)
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WARNINGS AND PRECAUTIONS
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Serious and potentially fatal cardiovascular (CV) thrombotic events, myocardial infarction, and stroke. Patients with known CV disease/risk factors may be at greater risk (5.1, 14.7, 17.2).
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Serious gastrointestinal (GI) adverse events, which can be fatal. The risk is greater in patients with a prior history of ulcer disease or GI bleeding, and in patients at high risk for GI events, especially the elderly. CELEBREX should be used with caution in these patients (5.4, 8.5, 14.7, 17.3).
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Elevated liver enzymes and, rarely, severe hepatic reactions. Discontinue use of CELEBREX immediately if abnormal liver enzymes persist or worsen (5.5, 17.4).
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New onset or worsening of hypertension. Blood pressure should be monitored closely during treatment with CELEBREX (5.2, 7.4, 17.2).
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Fluid retention and edema. CELEBREX should be used with caution in patients with fluid retention or heart failure (5.3, 17.6).
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Renal papillary necrosis and other renal injury with long term use. Use CELEBREX with caution in the elderly, those with impaired renal function, heart failure, liver dysfunction, and those taking diuretics, ACE-inhibitors, or angiotensin II antagonists (5.6, 7.4, 8.7, 17.6).
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Anaphylactoid reactions. Do not use CELEBREX in patients with the aspirin triad (5.7, 10, 17.7).
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Serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal and can occur without warning even without known prior sulfa allergy. Discontinue CELEBREX at first appearance of rash or skin reactions (5.8, 17.5).
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ADVERSE REACTIONS
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Most common adverse reactions in arthritis trials (>2% and >placebo): abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, rash (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
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DRUG INTERACTIONS
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Concomitant use of CELEBREX and warfarin may result in increased risk of bleeding complications. (7.1)
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Concomitant use of CELEBREX increases lithium plasma levels. (7.2)
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Concomitant use of CELEBREX may reduce the antihypertensive effect of ACE Inhibitors and angiotensin II antaonists (7.4)
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Use caution with drugs known to inhibit P450 2C9 or metabolized by 2D6 due to the potential for increased plasma levels (2.7, 8.4, 8.8, 12.3)
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USE IN SPECIFIC POPULATIONS
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Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation (5.9, 8.1, 17.8)
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See 17 for PATIENT COUNSELING INFORMATION and Medication Guide |
Revised: 05/2011 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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1 INDICATIONS AND USAGE
1.1 Osteoarthritis (OA)
1.2 Rheumatoid Arthritis (RA)
1.3 Juvenile Rheumatoid Arthritis (JRA)
1.4 Ankylosing Spondylitis (AS)
1.5 Acute Pain (AP)
1.6 Primary Dysmenorrhea (PD)
1.7 Familial Adenomatous Polyposis (FAP)
2 DOSAGE AND ADMINISTRATION
2.1 Osteoarthritis
2.2 Rheumatoid Arthritis
2.3 Juvenile Rheumatoid Arthritis
2.4 Ankylosing Spondylitis
2.5 Management of Acute Pain and Treatment of Primary Dysmenorrhea
2.6 Familial Adenomatous Polyposis
2.7 Special Populations
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Thrombotic Events
5.2 Hypertension
5.3 Congestive Heart Failure and Edema
5.4 Gastrointestinal (GI) Effects
5.5 Hepatic Effects
5.6 Renal Effects
5.7 Anaphylactoid Reactions
5.8 Skin Reactions
5.9 Pregnancy
5.10 Corticosteroid Treatment
5.11 Hematological Effects
5.12 Disseminated Intravascular Coagulation (DIC)
5.13 Preexisting Asthma
5.14 Laboratory Tests
5.15 GI Cancer in Familial Adenomatous Polyposis
5.16 Inflammation
5.17 Concomitant NSAID Use
6 ADVERSE REACTIONS
6.1 Pre-marketing Controlled Arthritis Trials
6.2 The Celecoxib Long-Term Arthritis Safety Study
6.3 Juvenile Rheumatoid Arthritis Study
6.4 Other Pre-Approval Studies
6.5 The APC and PreSAP Trials
7 DRUG INTERACTIONS
7.1 Warfarin
7.2 Lithium
7.3 Aspirin
7.4 ACE-inhibitors and Angiotensin II Antagonists
7.5 Fluconazole
7.6 Furosemide
7.7 Methotrexate
7.8 Concomitant NSAID Use
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Insufficiency
8.7 Renal Insufficiency
8.8 Poor Metabolizers of CYP2C9 Substrates
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Osteoarthritis
14.2 Rheumatoid Arthritis
14.3 Juvenile Rheumatoid Arthritis
14.4 Ankylosing Spondylitis
14.5 Analgesia, including Primary Dysmenorrhea
14.6 Familial Adenomatous Polyposis
14.7 Special Studies
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Medication Guide
17.2 Cardiovascular Effects
17.3 Gastrointestinal Effects
17.4 Hepatic Effects
17.5 Adverse Skin Reactions
17.6 Weight Gain and Edema
17.7 Anaphylactoid Reactions
17.8 Effects During Pregnancy
17.9 Preexisting Asthma
17.10 GI Cancer in Familial Adenomatous Polyposis
principal display panel - 100 mg bag
principal display panel - 200 mg bag
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FULL PRESCRIBING INFORMATION
Cardiovascular Risk
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CELEBREX may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All nonsteroidal anti-inflammatory drugs (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. (5.1,14.7)
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CELEBREX is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. (4, 5.1)
Gastrointestinal Risk
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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. (5.4)
1 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 and Precautions (5)]
1.1 Osteoarthritis (OA)
CELEBREX is indicated for relief of the signs and symptoms of OA [see Clinical Studies (14.1)]
1.2 Rheumatoid Arthritis (RA)
CELEBREX is indicated for relief of the signs and symptoms of RA [see Clinical Studies (14.2)]
1.3 Juvenile Rheumatoid Arthritis (JRA)
CELEBREX is indicated for relief of the signs and symptoms of JRA in patients 2 years and older [see Clinical Studies (14.3)]
1.4 Ankylosing Spondylitis (AS)
CELEBREX is indicated for the relief of signs and symptoms of AS [see Clinical Studies (14.4)]
1.5 Acute Pain (AP)
CELEBREX is indicated for the management of AP in adults [see Clinical Studies (14.5)]
1.6 Primary Dysmenorrhea (PD)
CELEBREX is indicated for the treatment of PD [see Clinical Studies (14.5)]
1.7 Familial Adenomatous Polyposis (FAP)
CELEBREX is indicated to reduce the number of adenomatous colorectal polyps in 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 Warnings and Precautions (5.15), Clinical Studies (14.6)]
2 DOSAGE AND ADMINISTRATION
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.
2.1 Osteoarthritis
For relief of the signs and symptoms of OA the recommended oral dose is 200 mg per day administered as a single dose or as 100 mg twice daily.
2.2 Rheumatoid Arthritis
For relief of the signs and symptoms of RA the recommended oral dose is 100 to 200 mg twice daily.
2.3 Juvenile Rheumatoid Arthritis
For the relief of the signs and symptoms of JRA the recommended oral dose for pediatric patients (age 2 years and older) is based on weight. For patients ≥10 kg to ≤25 kg the recommended dose is 50 mg twice daily. For patients >25 kg the recommended dose is 100 mg twice daily.
For patients who have difficulty swallowing capsules, the contents of a CELEBREX capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a level teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated conditions (2–8° C/ 35–45° F).
2.4 Ankylosing Spondylitis
For the management of the signs and symptoms of AS, the recommended dose of CELEBREX is 200 mg daily in 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.
2.5 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.
2.6 Familial Adenomatous Polyposis
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.
2.7 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 50%. The use of CELEBREX in patients with severe hepatic impairment is not recommended [see Warnings and Precautions (5.5), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Poor Metabolizers of CYP2C9 Substrates: Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers. Consider using alternative management in JRA patients who are poor metabolizers. [see Use in Specific populations (8.8), and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
Capsules: 50 mg, 100 mg, 200 mg and 400 mg
4 CONTRAINDICATIONS
CELEBREX is contraindicated:
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In patients with known hypersensitivity to celecoxib, aspirin, or other NSAIDs.
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In patients who have demonstrated allergic-type reactions to sulfonamides.
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In patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe anaphylactoid reactions to NSAIDs, some of them fatal, have been reported in such patients [see Warnings and Precautions (5.7, 5.13)].
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For the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Thrombotic Events
Chronic use of CELEBREX may cause an increased risk of serious adverse cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. In the APC (Adenoma Prevention with Celecoxib) trial, the hazard ratio for the composite endpoint of cardiovascular death, MI, or stroke was 3.4 (95% CI 1.4 – 8.5) for CELEBREX 400 mg twice daily and 2.8 (95% CI 1.1 – 7.2) with CELEBREX 200 mg twice daily compared to placebo. Cumulative rates for this composite endpoint over 3 years were 3.0% (20/671 subjects) and 2.5% (17/685 subjects), respectively, compared to 0.9% (6/679 subjects) with placebo treatment. The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction [see Clinical Studies (14.7)].
All NSAIDs, both COX-2 selective and non-selective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with CELEBREX, the lowest effective dose should be used for the shortest duration consistent with individual patient treatment goals. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV toxicity and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and CELEBREX does increase the risk of serious GI events [see Warnings and Precautions (5.4)].
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 (4)].
5.2 Hypertension
As with all NSAIDs, CELEBREX can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including CELEBREX, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with CELEBREX and throughout the course of therapy. The rates of hypertension from the CLASS trial in the CELEBREX, ibuprofen and diclofenac-treated patients were 2.4%, 4.2% and 2.5%, respectively [see Clinical Studies (14.7)].
5.3 Congestive Heart Failure and Edema
Fluid retention and edema have been observed in some patients taking NSAIDs, including CELEBREX [see Adverse Reactions (6.1)]. In the CLASS study [see Clinical Studies (14.7)], 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.
5.4 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. Thes |
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