Class: Cyclooxygenase-2 (COX-2) Inhibitors
Chemical Name: 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
CAS Number: 184007-95-2
- Cardiovascular Risk
Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 500 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)
Contraindicated in the setting of CABG surgery.508
- 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 Celecoxib
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 Thrombotic Effects under Cautions.)
Celecoxib 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 Celecoxib
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
In the setting of CABG surgery.508
Cardiovascular Thrombotic Effects
NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.1 103 104 113 116 122 123 129 130 131 134 137 138 139 140 141 146 147 148 500 502 508 Current evidence suggests cardiovascular risk with celecoxib may be dose related, with dosages >200 mg daily associated with greater risk.147 157 158 512
Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500
Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508
In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508
Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511
Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.146 147 148 151 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500
Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.1 102 112 500 508
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
Some clinicians state that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 103 133 134 135 139 141 502 508 (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
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
NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)
Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508
Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507
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
Not known whether long-term cardiovascular risks in children exposed to celecoxib are similar to those observed in adults receiving celecoxib or other NSAIAs.508 (See Cardiovascular Thrombotic Effects under Cautions.)
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 Celecoxib
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
Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.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 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
Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.508
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.1 (See Cautions.)
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.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS DI Essentials. © Copyright 2017, Selected Revisions November 21, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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