Generic Name: Celecoxib
Class: Cyclooxygenase-2 (COX-2) Inhibitors
Chemical Name: 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
CAS Number: 184007-95-2
AUDIENCE: Health Professional, Consumer
ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: for a list of non-aspirin nonsteroidal anti-inflammatory drug products.
Prescription NSAID labels will be revised to reflect the following information:
The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.
RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.
For more information visit the FDA website at: and .
- Cardiovascular Risk
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.1
- GI Risk
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)
Uses for Celebrex
Consider potential benefits and risks of celecoxib therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1
Rheumatoid Arthritis in Adults
Reduction of the number of adenomatous colorectal polyps (colorectal adenomas) in adults with familial adenomatous polyposis (FAP); used as an adjunct to usual care.1 60 Not known whether celecoxib reduces the risk of colorectal, duodenal, or other FAP-related cancers.1
Has been investigated for the prevention of colorectal adenomas in patients without a history of FAP†.149 150 Use of celecoxib reduces the risk of recurrent colorectal adenomas;149 150 not known whether celecoxib reduces the risk of colorectal cancer.149 150 Routine use not recommended because of the potential for serious cardiovascular events.149
Cardiovascular Risk Reduction
Not a substitute for aspirin in the prevention of adverse cardiovascular events (MI).1 (See Cardiovascular Effects under Cautions.)
Celebrex Dosage and Administration
Consider potential benefits and risks of celecoxib therapy as well as alternative therapies before initiating therapy with the drug.1
Administer dosages up to 200 mg twice daily without regard to meals; administer higher dosages (400 mg twice daily) with food.1
For patients who have difficulty swallowing capsules, the capsule may be opened and the contents sprinkled onto a level teaspoonful of applesauce at room temperature or cooler, and the mixture swallowed immediately with water.1
To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1
Attempt to titrate to the lowest effective dosage in adults with arthritis.1
Children ≥2 years of age weighing 10–25 kg: 50 mg twice daily.1
Children ≥2 years of age weighing >25 kg: 100 mg twice daily.1
No additional benefit from dosages >200 mg daily.1
Rheumatoid Arthritis in Adults
No additional benefit from higher dosages (400 mg twice daily).1
Initially, 200 mg daily as a single dose or in 2 equally divided doses.1 If no response observed after 6 weeks, increase to 400 mg daily.1 If no response observed after 400 mg daily for 6 weeks, response is unlikely; consider alternative therapies.1
Reduce dosage by 50% in patients with moderate hepatic impairment; not recommended in patients with severe impairment.1
Dosage adjustment based solely on age is not necessary; initiate at lowest recommended dosage in geriatric patients weighing <50 kg.1
Cautions for Celebrex
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Known hypersensitivity to celecoxib, sulfonamides, or any ingredient in the formulation.1
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1
Treatment of perioperative pain in the setting of CABG surgery.1
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.1 103 104 113 116 122 123 129 130 131 134 137 138 139 140 141 146 147 148 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.146 147 148 Current evidence suggests that use of celecoxib at dosages >200 mg daily is associated with increased cardiovascular risk, while the potential risk is less clear at dosages of ≤200 mg daily.146 148 157 158
Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).133
Not known whether long-term use in children is associated with increased cardiovascular risk.1
Use celecoxib with caution and careful monitoring (e.g., monitor for development of cardiovascular events).1 102 112 Until more data are available, a selective COX-2 inhibitor remains an appropriate choice for patients at low cardiovascular risk who have had serious GI events, especially while receiving a prototypical NSAIA.112 121 128 145 May be prudent to avoid use of selective COX-2 inhibitors in patients who have or are at risk for cardiovascular disease.112 121 124 128 142 143
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 103 133 134 135 139 141 (See Specific Drugs under Interactions.)
Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)
Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1
Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1
Potential for overt renal decompensation.1 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 46 153 (See Renal Impairment under Cautions.)
Celecoxib not shown to reduce risk of GI cancer or need for prophylactic colectomy or other FAP-related surgery in patients with FAP; usual care (i.e., endoscopic surveillance, prophylactic colectomy, other FAP-related surgery) should not be altered.1
Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.1
Immediate medical intervention and discontinuance for anaphylaxis.1
Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1
Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning and in patients without a history of sulfonamide sensitivity.1 144 Discontinue at first appearance of rash or any other sign of hypersensitivity (blisters, fever, pruritus).1
Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1
Elevations of serum ALT or AST reported.1
Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.1
No effect on platelet counts, prothrombin time, or partial thromboplastin time; usual dosages do not affect platelet aggregation.1
Modest increases in aPTT reported in children with systemic onset juvenile rheumatoid arthritis (active systemic disease not present); risk of disseminated intravascular coagulation.1 Use with caution and monitor coagulation tests in these children.1
Potential for increased plasma celecoxib concentrations in patients with poor metabolizer phenotype of CYP2D6; use with caution in patients with known or suspected poor metabolizer phenotype.1
Prescribing and Dispensing Precautions
Ensure accuracy of prescription; similarity in spelling of Celebrex (celecoxib), Celexa (citalopram hydrobromide), and Cerebyx (fosphenytoin sodium) may result in errors.34
Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1
May mask certain signs of infection.1
Obtain CBC and chemistry profile periodically during long-term use.1
Safety and efficacy in children 2–17 years of age with pauciarticular course, polyarticular course, or systemic onset juvenile rheumatoid arthritis supported by evidence from an active-controlled clinical study.1 Safety and efficacy not established in children <2 years of age, those weighing <10 kg, or children with active systemic disease.1 Not studied beyond 6 months.1
Children with systemic onset juvenile rheumatoid arthritis: Risk of abnormal coagulation test results; modest prolongation of aPTT reported.1 Risk of disseminated intravascular coagulation.1 Use with caution in these children; monitor coagulation tests.1
Use not recommended in patients with severe hepatic impairment.1
Reduced dosage recommended in patients with moderate hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)
Common Adverse Effects
Adults: Abdominal pain, diarrhea, dyspepsia, headache, nausea, sinusitis, upper respiratory tract infection.1
Children: Headache, fever, abdominal pain, cough, nasopharyngitis, nausea, arthralgia, diarrhea, vomiting.1
Interactions for Celebrex
Metabolized by CYP2C9.77
Inhibits CYP2D6; does not inhibit CYP2C9, CYP2C19, or CYP3A4.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Reduced BP response to ACE inhibitor1
Angiotensin II receptor antagonists
Reduced BP response to angiotensin II receptor antagonists153
Antacids (magnesium- or aluminum-containing)
Diuretics (furosemide, thiazides)
Reduced natriuretic effects1
Increased plasma celecoxib concentrations1
Initiate celecoxib at lowest recommended dosage1
Pharmacokinetic interaction unlikely1
Pharmacokinetic interaction unlikely1
Increased plasma lithium concentrations1
Monitor for lithium toxicity when initiating or discontinuing celecoxib1
Pharmacokinetics of methotrexate not altered1
Pharmacokinetic interaction unlikely1
Pharmacokinetic interaction unlikely1
Single doses provide pain relief within 60 minutes.1
Bioavailability increased 10–20% and time to reach peak plasma concentration delayed 1–2 hours when 200-mg capsule is administered with a high-fat meal.1 2 Administration of dosages of 400 mg twice daily with food improves absorption.1
Administration as mixture in applesauce does not alter AUC, peak plasma concentration, or time to peak plasma concentration.1
Not well characterized.1
Plasma Protein Binding
Pediatric patients: Oral clearance increases in less-than-proportional manner with increasing weight; clearance predicted to be 40 or 24% lower in pediatric patients weighing 10 or 25 kg, respectively, than in a 70-kg adult.1
11 hours under fasting conditions.1
25°C (may be exposed to 15–30°C).1
Mixture of capsule contents in applesauce is stable for 6 hours when refrigerated.1
Related structurally and pharmacologically to rofecoxib and valdecoxib (COX-2 inhibitors no longer commercially available in the US); differs structurally and, to some extent, pharmacologically from prototypical NSAIAs, which inhibit COX-1 and COX-2.1 2 3 4 5 8 11 41 52
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1
Risk of serious cardiovascular events with long-term use.1
Risk of GI bleeding and ulceration.1
Risk of hepatotoxicity.1
Not a substitute for aspirin in the prevention of adverse cardiovascular events.1
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1
Importance of discontinuing celecoxib and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
For patients with FAP, importance of continuing usual care.1
Importance of informing patients of other important precautionary information. (See Cautions.)1
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Celebrex (with povidone)
Celebrex (with povidone)
Celebrex (with povidone)
Celebrex (with povidone)
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
CeleBREX 100MG Capsules (PFIZER U.S.): 30/$90.99 or 90/$249.97
CeleBREX 200MG Capsules (PFIZER U.S.): 30/$142.99 or 90/$409.97
CeleBREX 400MG Capsules (PFIZER U.S.): 30/$208.98 or 90/$601.98
CeleBREX 50MG Capsules (PFIZER U.S.): 30/$49.99 or 90/$124.97
AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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