Class: Cyclooxygenase-2 (COX-2) Inhibitors
- COX-2 Inhibitors
Chemical Name: 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
CAS Number: 184007-95-2
Medically reviewed by Drugs.com. Last updated on Nov 9, 2020.
AUDIENCE: Consumer, Patient, Health Professional, Pharmacy
ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.
For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.
For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: [Web]. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.
are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.
are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.
work by blocking the production of certain chemicals in the body that cause inflammation.
are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.
Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.
If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.
Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: [Web], to find out if the medicines contain NSAIDs.
Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.
Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.
Health Care Professionals
FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.
The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.
Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.
- 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
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.
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
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.
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
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
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 2021, Selected Revisions November 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Pfizer. Celebrex (celecoxib) capsules prescribing information. New York, NY; 2006 Dec.
2. G.D. Searle & Co. Celebrex (celecoxib) formulary information. Skokie, IL; 1999 Feb 8.
3. Anon. Celecoxib for arthritis. Med Lett Drugs Ther. 1999; 41:11-2. http://www.ncbi.nlm.nih.gov/pubmed/9949762?dopt=AbstractPlus
4. Gierse JK, McDonald JJ, Hauser SD et al. A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. J Biol Chem. 1996; 271:15810-4. http://www.ncbi.nlm.nih.gov/pubmed/8663121?dopt=AbstractPlus
5. Seibert K, Zhang Y, Leahy K et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA. 1994; 91:12013-7. http://www.ncbi.nlm.nih.gov/pubmed/7991575?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=45366&blobtype=pdf
6. Funck-Brentano C, Thomas G, Jacqz-Aigrain E et al. Polymorphism of dextromethorphan metabolism: relationships between phenotype, genotype and response to the administration of encainide in humans. J Pharmacol Exp Ther. 1992; 263:780-6. http://www.ncbi.nlm.nih.gov/pubmed/1432700?dopt=AbstractPlus
7. McAdam BF, Catella-Lawson F, Mardini IA et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci USA. 1999; 96:272-7. http://www.ncbi.nlm.nih.gov/pubmed/9874808?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=15129&blobtype=pdf
8. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. http://www.ncbi.nlm.nih.gov/pubmed/9929039?dopt=AbstractPlus
9. Simon LS, Lanza FL, Lipsky PE et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum. 1998; 41:1591-602. http://www.ncbi.nlm.nih.gov/pubmed/9751091?dopt=AbstractPlus
10. Lipsky PE, Isakson PC. Outcome of specific COX-2 inhibition in rheumatoid arthritis. J Rheumatol. 1997; 24(Suppl 49):9-14. http://www.ncbi.nlm.nih.gov/pubmed/9002004?dopt=AbstractPlus
11. Penning TD, Talley JJ, Bertenshaw SR et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib). J Med Chem. 1997; 40:1347-65. http://www.ncbi.nlm.nih.gov/pubmed/9135032?dopt=AbstractPlus
12. Markind JE (G. D. Searle, Skokie, Ill): Personal communication; 1999 May 7.
13. G.D. Searle. Response to Wall Street Journal article regarding Celebrex. Skokie, Ill; 1999 Apr 20. Press release from website (http://www.searlehealthnet.com/pr/042099.htm).
14. Anon. Searle responds to Journal report on Celebrex side effects. Skokie, Ill; 1999 Apr 22. Press release from website (http://www.pslgroup.com:80/dg/f8f2e.htm).
15. Kawamori T, Rao CV, Seibert K et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 1998; 58:409-12. http://www.ncbi.nlm.nih.gov/pubmed/9458081?dopt=AbstractPlus
16. McAdam BF, Kapoor S, Catella-Lawson F et al. Selective inhibition of monocyte COX-2 vs platelet COX-1 in humans. Circulation. 1997; 96(Suppl):I-557.
17. Crofford LJ, Wilder RL, Ristimäki AP et al. Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: effects of interleukin-1β, phorbol ester, and corticosteroids. J Clin Invest. 1994; 93:1095-101. http://www.ncbi.nlm.nih.gov/pubmed/8132748?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=294048&blobtype=pdf
18. Lane NE. Pain management in osteoarthritis: the role of COX-2 inhibitors. J Rheumatol. 1997; 24(Suppl 49):20-4. http://www.ncbi.nlm.nih.gov/pubmed/9002006?dopt=AbstractPlus
19. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.
20. Mengle-Gaw L, Hubbard RC, Karim A et al. A study of the platelet effects of SC-58635, a novel COX-2-selective inhibitor. Arthritis Rheum. 1997; 40:S93.
21. Geis GS, Hubbard R, Callison D et al. Safety and efficacy of celecoxib, a specific COX-2 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum. 1998; 41:S364. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1602062&blobtype=pdf
22. Hubbard RC, Koepp R, Yu SS et al. Pilot efficacy of SC-58635, a COX-2-selective inhibitor, in rheumatoid arthritis. Arthritis Rheum. 1997; 40:S51.
23. Karim A, Tolbert D, Burton E et al. SC-58635 (celecoxib): a highly selective inhibitor of cyclooxygenase-2, disposition kinetics in man and identification of its major CYP450 isozyme in its biotransformation. Pharm Res. 1997; 14(Suppl):S617.
24. Geis GS, Stead H, Morant S et al. Efficacy and safety of celecoxib, a specific COX-2 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum. 1998; 41:S316. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1602062&blobtype=pdf
25. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38:727-35. http://www.ncbi.nlm.nih.gov/pubmed/7779114?dopt=AbstractPlus
26. Felson DT, Anderson JJ, Boers M et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum. 1993; 36:729-40. http://www.ncbi.nlm.nih.gov/pubmed/8507213?dopt=AbstractPlus
27. Felson DT, Anderson JJ, Lange MLM et al. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent? Arthritis Rheum. 1998; 41:1564-70. (IDIS 411264)
28. Hubbard RC, Geis GS, Callison DA et al. Efficacy and safety of celecoxib, a specific COX-2 inhibitor, in osteoarthritis (OA) and rheumatoid (RA). J Rheumatol. 1998; 25(Suppl 52):6. http://www.ncbi.nlm.nih.gov/pubmed/9458195?dopt=AbstractPlus
29. Hubbard R, Geis GS, Woods E et al. Efficacy, tolerability, and safety of celecoxib, a specific COX-2 inhibitor, in osteoarthritis. Arthritis Rheum. 1998; 41:S196. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1602062&blobtype=pdf
30. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002; 46:328-46. http://www.ncbi.nlm.nih.gov/pubmed/11840435?dopt=AbstractPlus
31. Lane NE, Thompson JM. Management of osteoarthritis in the primary-care setting: an evidence-based approach to treatment. Am J Med. 1997; 103(Suppl 6A):25-30S. http://www.ncbi.nlm.nih.gov/pubmed/9236482?dopt=AbstractPlus
32. Altman RD, Hochberg MC, Moskowitz RW et al. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000; 43:1905-15. http://www.ncbi.nlm.nih.gov/pubmed/11014340?dopt=AbstractPlus
33. Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumtoid arthritis. The CLASS study: a randomized controlled trial. JAMA. 2000; 284:1247-55. http://www.ncbi.nlm.nih.gov/pubmed/10979111?dopt=AbstractPlus
34. Sharpe R. Monsanto, FDA are trying to overcome confusion over name of arthritis drug. Wall St J. 1999 Apr 15.
35. Anon. Celebrex wins “unclear” advantage from FDA: backhanded ok for GI safety. F-D-C Rep. 1999; Jan 4:33-4.
36. Lithium interactions. In: Hansten PD, Horn JR. Drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:223, 327, 332, 358, 367-369, 371.
37. Smith CJ, Zhang Y, Koboldt CM et al. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA. 1998; 95:13313-8. http://www.ncbi.nlm.nih.gov/pubmed/9789085?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=23795&blobtype=pdf
38. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase—a review. Prostaglandins Lipid Mediators. 1998; 56:341-61.
39. Anderson GD, Hauser SD, McGarity KL et al. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. J Clin Invest. 1996; 97:2672-9. http://www.ncbi.nlm.nih.gov/pubmed/8647962?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=507355&blobtype=pdf
40. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95. http://www.ncbi.nlm.nih.gov/pubmed/9365818?dopt=AbstractPlus
41. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. http://www.ncbi.nlm.nih.gov/pubmed/8967954?dopt=AbstractPlus
42. Hubbard RC, Mehlisch DR et al. SC-58635, a highly selective inhibitor of COX-2, is an effective analgesic in an acute post surgical pain model. J Invest Med. 1996; 44:293A.
43. Mehlisch DR, Hubbard RC, Isakson P et al. Analgesic efficacy and plasma levels of a highly selective inhibitor of COX-2 (SC-58635; SC) in patients with post-surgical dental pain. Clin Pharmacol Ther. 1997; 61:195.
44. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy. 1998; 18:84-112. http://www.ncbi.nlm.nih.gov/pubmed/9469685?dopt=AbstractPlus
45. Angiotensin-converting enzyme inhibitor interactions: nonsteroidal anti-inflammatory drugs (NSAIDSs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:131-2.
46. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.
47. Lanza FL, Rack MF, Callison DA et al. A pilot endoscopic study of the gastroduodenal effects of SC-58635, a novel COX-2 selective inhibitor. Gastroenterology. 1997; 112:A194. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3005357&blobtype=pdf
48. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106:37S-42. http://www.ncbi.nlm.nih.gov/pubmed/10390126?dopt=AbstractPlus
49. Geis GS. Update on clinical developments with celecoxib, a new specific COX-2 inhibitor: what can we expect? J Rheumatol. 1999; 26(Suppl 56):31-6.
50. Pfizer, New York, NY: Personal communication.
51. Reviewers’ comments (personal observations).
52. Merck & Co. Vioxx (rofecoxib) tablets and oral suspension prescribing information. Whitehouse Station, NJ: 2000 Jul.
53. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Ann Rev Pharmacol Toxicol. 1998; 38:97-120.
54. Wolfe MM, Lichtenstein DR, Singh G. Gastroinestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. http://www.ncbi.nlm.nih.gov/pubmed/10369853?dopt=AbstractPlus
55. Karim A, Tolbert D, Piergies A et al. Celecoxib, a specific COX-2 inhibitor, lacks significan drug-drug interactions with methotrexate or warfarin. Arthritis Rheum. 1998; 41(Suppl):S315. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1602062&blobtype=pdf
56. Bello A. Dear health care professional letter regarding updated labeling for Celebrex (celecoxib) on prothrombin time increases with concomitant warfarin therapy. Skokie, IL: Searle; 1999 May.
57. Food and Drug Administration Center for Drug Evaluation and Research: questions and answers about Celebrex labeling change—warfarin interaction. 1999; June 1.
58. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis. 2000: 35:937-40.
59. Dunn MJ. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis. 2000: 35:976-7. Editorial.
60. Steinbach G, Lynch PM, RKS Phillips et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000; 342:1946-52. http://www.ncbi.nlm.nih.gov/pubmed/10874062?dopt=AbstractPlus
61. Sheehan KM, Sheahan K, O’Donoghue DP et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA. 1999; 282:1254-7. http://www.ncbi.nlm.nih.gov/pubmed/10517428?dopt=AbstractPlus
62. Lanza FL, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. http://www.ncbi.nlm.nih.gov/pubmed/9820370?dopt=AbstractPlus
63. Goldstein JL, Silverstein FE, Agrawal NM et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol. 2000; 95:1681-90. http://www.ncbi.nlm.nih.gov/pubmed/10925968?dopt=AbstractPlus
64. Bensen WG, Fiechtner JJ, McMillen JI et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc. 1999; 74:1095-1105. http://www.ncbi.nlm.nih.gov/pubmed/10560596?dopt=AbstractPlus
65. Emery P, Zeidler H, Kvien TK et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomized double-blind comparison. Lancet. 1999; 354:2106-11. http://www.ncbi.nlm.nih.gov/pubmed/10609815?dopt=AbstractPlus
66. Simon LS, Weaver AL, Graham DY et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled study. JAMA. 1999; 282:1921-8. http://www.ncbi.nlm.nih.gov/pubmed/10580457?dopt=AbstractPlus
67. Pincus T, O’Dell JR, Kremer JM. Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: a preventive strategy. Ann Intern Med. 1999; 131:768-74. http://www.ncbi.nlm.nih.gov/pubmed/10577301?dopt=AbstractPlus
68. Reviewer comments (personal observations) on etanercept.
69. Peterson WL, Cryer B. Cox-1-sparing NSAIDs–is the enthusiasm justified? JAMA. 1999; 282:1961-3. Editorial.
70. Beejay U, Wolfe MM. Cyclooxygenase 2 selective inhibitors: panacea or flash in the pan? Gastroenterology. 1999; 117:1002-14. Editorial.
71. Mizuno H, Sakamoto C, Matsuda K et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology. 1997; 112:387-97. http://www.ncbi.nlm.nih.gov/pubmed/9024292?dopt=AbstractPlus
72. Stenson WF. Cyclooxygenase 2 and wound healing in the stomach. Gastroenterology. 1997; 112:645-8. http://www.ncbi.nlm.nih.gov/pubmed/9024317?dopt=AbstractPlus
73. Schmassmann A, Peskar BM, Stettler C et al. Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats. Br J Pharmacol,. 1998; 123:795-804.
74. Anon. Selective COX-2 inhibitors and bleeding risk: an additional note. Med Lett Drugs Ther. 2000; 42:92.
75. Reddy BS, Hirose Y, Lubet R et al. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res. 2000; 60:293-7. http://www.ncbi.nlm.nih.gov/pubmed/10667579?dopt=AbstractPlus
76. Fournier DB, Gordon GB. COX-2 and colon cancer: potential targets for chemoprevention. J Cell Biochem. 2000; 34:97-102.
77. Jacoby RF, Seibert K, Cole CE et al. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 2000; 60:5040-4. http://www.ncbi.nlm.nih.gov/pubmed/11016626?dopt=AbstractPlus
78. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. http://www.ncbi.nlm.nih.gov/pubmed/10887424?dopt=AbstractPlus
79. Food and Drug Administration. CLASS Advisory Committee meeting. Rockville, MD; Feb 2001. From FDA web site (http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3677tl.rtf)
80. Fitzgerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001; 345:433-42. http://www.ncbi.nlm.nih.gov/pubmed/11496855?dopt=AbstractPlus
81. Gottlieb S. Researchers deny any attempt to mislead public over JAMA article on arthritis drug. BMJ. 2001; 323:301. http://www.ncbi.nlm.nih.gov/pubmed/11498480?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1120924&blobtype=pdf
82. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001; 286:954-9. http://www.ncbi.nlm.nih.gov/pubmed/11509060?dopt=AbstractPlus
83. Levy MB, Fink JN. Anaphylaxis to celecoxib. Ann Allergy Asthma Immunol. 2001; 87:72-3. http://www.ncbi.nlm.nih.gov/pubmed/11476468?dopt=AbstractPlus
84. Fye KH, Crowley E, Berger TG et al. Celecoxib-induced Sweet’s syndrome. J Am Acad Dermatol. 2001; 45:300-2. http://www.ncbi.nlm.nih.gov/pubmed/11464196?dopt=AbstractPlus
85. O’Beirne JP, Cairns SR. Cholestatic hepatitis in association with celecoxib. BMJ. 2001; 323:23. http://www.ncbi.nlm.nih.gov/pubmed/11440939?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=34328&blobtype=pdf
86. Graham MG. Acute renal failure related to high-dose celecoxib. Ann Intern Med. 2001; 135:69-70. http://www.ncbi.nlm.nih.gov/pubmed/11434756?dopt=AbstractPlus
87. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.
88. Morrison BW, Daniels SE, Kotey P et al. Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled trial. Obstet Gynecol. 1999; 94:504-8. http://www.ncbi.nlm.nih.gov/pubmed/10511349?dopt=AbstractPlus
89. Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol. 1993; 169:1255-65. http://www.ncbi.nlm.nih.gov/pubmed/8238194?dopt=AbstractPlus
90. Bieglmayer C, Hofer G, Kainz C et al. Concentrations of various arachidonic acid metabolites in menstrual fluid are associated with menstrual pain and are influenced by hormonal contraceptives. Gynecol Endocrinol. 1995; 9:307-12. http://www.ncbi.nlm.nih.gov/pubmed/8629459?dopt=AbstractPlus
91. Chan WY, Fuchs F, Powell AM. Effects of naproxen sodium on menstrual prostaglandin and primary dysmenorrhea. Obstet Gynecol. 1983; 61:285-91. http://www.ncbi.nlm.nih.gov/pubmed/6571974?dopt=AbstractPlus
92. Lim H, Paria BC, Das SK et al. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell. 1997; 91:197-208. http://www.ncbi.nlm.nih.gov/pubmed/9346237?dopt=AbstractPlus
93. in’t Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001; 345:1515-21. http://www.ncbi.nlm.nih.gov/pubmed/11794217?dopt=AbstractPlus
94. Breitner JCS, Zandi PP. Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med. 2001; 345:1567-8. Editorial.
95. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47:425-32. http://www.ncbi.nlm.nih.gov/pubmed/8757015?dopt=AbstractPlus
96. Beard CM, Waring SC, O’sBrien PC et al. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease : a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998; 73:951-5. http://www.ncbi.nlm.nih.gov/pubmed/9787743?dopt=AbstractPlus
97. in’t Veld BA, Launer LJ, Hoes AW et al. NSAIDs and incident Alzheimer’s disease: the Rotterdam Study. Neurobiol Aging. 1998; 19:607-11. http://www.ncbi.nlm.nih.gov/pubmed/10192221?dopt=AbstractPlus
98. Stewart WF, Kawas C, Corrada M et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology. 1997; 48:626-32. http://www.ncbi.nlm.nih.gov/pubmed/9065537?dopt=AbstractPlus
99. Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomized controlled trials. BMJ; 325:619-23.
100. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10. http://www.ncbi.nlm.nih.gov/pubmed/12501222?dopt=AbstractPlus
101. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. http://www.ncbi.nlm.nih.gov/pubmed/12501230?dopt=AbstractPlus
102. Clark DWJ, Layton D, Shakir SAW. Do some inhibitors of COX-2 increase the risk of thromboembolic events? Drug Safety. 2004; 27:427-56.
103. Bresalier RS, Sandler RS, Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005; 352:1092-102. http://www.ncbi.nlm.nih.gov/pubmed/15713943?dopt=AbstractPlus
104. Merck. Merck announces voluntary worldwide withdrawal of Vioxx. Whitehouse Station, NJ; 2004 Sep 30. Press release.
105. Couzin J. Drug safety: withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science. 2004; 306:384-5. http://www.ncbi.nlm.nih.gov/pubmed/15486258?dopt=AbstractPlus
106. Pfizer. Pfizer to sponsor major new Celebrex clinical trial. New York, NY; 2004 Oct 18. Press release.
107. Solomon D, Kavanaugh A, Matteson E L. Cardiovascular complications related to COX-2 inhibitors. From the American College of Rheumatology website (http://www.rheumatology.org). Accessed 2004 Oct 25.
108. Solomon DH, Schneeweiss S, Glynn RJ et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation. 2004; 109:2068-73. http://www.ncbi.nlm.nih.gov/pubmed/15096449?dopt=AbstractPlus
109. Food and Drug Administration. Consultation NDA 21-042, S-007: review of cardiovascular safety data: rofecoxib. Rockville, MD: 2001 Feb 1. From the FDA website (http://www.fda.gov). Accessed 2004 Oct 25.
110. Food and Drug Administration. CLASS Advisory Committee briefing document. Rockville, MD: 2001 Feb 7. From the FDA website (http://www.fda.gov). Accessed 2004 Oct 25.
111. Pfizer. Comparative studies with Vioxx (rofecoxib) in cardiovascular safety. New York, NY; 2004 Aug.
112. FitzGerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004: 351:1709-11.
113. Ott E, Nussmeier NA, Duke P C et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2003; 125:1481-92. http://www.ncbi.nlm.nih.gov/pubmed/12830070?dopt=AbstractPlus
114. Pfizer. The overall cardiovascular safety profile: Bextra. New York, NY; 2004 Nov 1.
115. White WB, Strand V, Roberts R et al. Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis. Am J Ther. 2004; 11:244-50. http://www.ncbi.nlm.nih.gov/pubmed/15266215?dopt=AbstractPlus
116. Bombardier C, Laine L, Reicin et al. Compariosn of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000; 343:1520-8. http://www.ncbi.nlm.nih.gov/pubmed/11087881?dopt=AbstractPlus
117. Anon. What about Celebrex? Med Lett Drugs Ther. 2004; 46:87-8.
118. Juni P, Nartey L, Reichenbach S et al. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004; 364:2021-9. http://www.ncbi.nlm.nih.gov/pubmed/15582059?dopt=AbstractPlus
119. White WB, Raich G, Borer JS et al. Cardiovascular events in arthritis trials of the cyclooxygenase-2 inhibitor celecoxib. Am J Cardiol. 2003; 92:411-8. http://www.ncbi.nlm.nih.gov/pubmed/12914871?dopt=AbstractPlus
120. Pfizer. Pfizer provides information to healthcare professionals about its Cox-2 medicine Bextra (valdecoxib). New York, NY: 2004 Oct 15. Press release.
121. Reviewers’ comments (personal observations) on COX-2 inhibitors and issue of potential cardiovascular risk.
122. Ray WA, Stein CM, Daugherty JR et al. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet. 2002; 360:1071-3. http://www.ncbi.nlm.nih.gov/pubmed/12383990?dopt=AbstractPlus
123. Graham DJ, Campen D, Hui R et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005; 365:475-81. http://www.ncbi.nlm.nih.gov/pubmed/15705456?dopt=AbstractPlus
124. Bing RJ. Cyclooxygenase-2 inhibitors: is there an association with coronary or renal events? Current Atherosclerosis Rep. 2003; 5:114-7.
125. White WB, Faich G, Whelton A et al. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol. 2002; 89:425-30. http://www.ncbi.nlm.nih.gov/pubmed/11835924?dopt=AbstractPlus
126. Pfizer, New York, NY. Personal communication on COX-2 inhibitors and issue of potential cardiovascular risk.
127. Kimmel SE, Berlin JA, Reilly M et al. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med. 2005; 142:157-64. http://www.ncbi.nlm.nih.gov/pubmed/15684203?dopt=AbstractPlus
128. Finckh A, Aronson MD. Cardiovascular risks of cyclooxygenase-2 inhibitors: where we stand now. Ann Intern Med. 2005; 142:212-4. http://www.ncbi.nlm.nih.gov/pubmed/15684210?dopt=AbstractPlus
129. Burklow J, Ralbovsky D. NIH Halts use of COX-2 inhibitor in large cancer prevention trial. NIH News. 2004 Dec 17.
130. US Food and Drug Administration. FDA statement on the halting of a clinical trial of the Cox-2 inhibitor Celebrex. Press release. Rockville, MD; 2004 Dec 17.
131. Pfizer. Pfizer statement on new information regarding cardiovascular safety of Celebrex. Press release. New York, NY; 2004 Dec 17.
132. Dougados M, Behier JM, Jolchine I et al. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Arthritis Rheum. 2001; 44:180-5. http://www.ncbi.nlm.nih.gov/pubmed/11212158?dopt=AbstractPlus
133. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.
134. Lévesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Intern Med. 2005; 142:481-9. http://www.ncbi.nlm.nih.gov/pubmed/15809459?dopt=AbstractPlus
135. Solomon SD, McMurray JJV, Pfeffer MA et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005; 352:1071-80. http://www.ncbi.nlm.nih.gov/pubmed/15713944?dopt=AbstractPlus
136. Anon. Use of non-steroidal anti-inflammatory drugs suspended in large Alzheimer’s disease prevention trial. NIH News. 2004 Dec 20.
137. Nussmeier NA, Whelton AA, Brown MT et al. Complications of the COX-2 inhibitors paracoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005; 352:1081-91. http://www.ncbi.nlm.nih.gov/pubmed/15713945?dopt=AbstractPlus
138. Shaya FT, Blume SW, Blanchette CM et al. Selective cyclooxygenase-2 inhibition and cardiovascular effects: an observational study of a Medicaid population. Arch Intern Med. 2005; 165:181-6. http://www.ncbi.nlm.nih.gov/pubmed/15668364?dopt=AbstractPlus
139. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005; 330:1366-72. http://www.ncbi.nlm.nih.gov/pubmed/15947398?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=558288&blobtype=pdf
140. Johnson SP, Larsson H, Tarone RE et al. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-controlled study. Arch Intern Med. 2005; 165:978-84. http://www.ncbi.nlm.nih.gov/pubmed/15883235?dopt=AbstractPlus
141. Farkouh ME, Kirshner H, Harrington RA et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet. 2004; 364:675-84. http://www.ncbi.nlm.nih.gov/pubmed/15325832?dopt=AbstractPlus
142. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (http://www.rheumatology.org). Accessed 2005 Oct 12.
143. Bennett JS, Daugherty A, Herrington D et al. The use of nonsteroidal anti-inflammatory drugs (NSAIDs); a Science Advisory from the American Heart Association. Circulation. 2005; 111:1713-16. http://www.ncbi.nlm.nih.gov/pubmed/15781731?dopt=AbstractPlus
144. La Grenade L, Lee L, Weaver J et al. Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrosis in association with selective COX-2 inhibitors. Drug Saf. 2005; 28:917-24. http://www.ncbi.nlm.nih.gov/pubmed/16180941?dopt=AbstractPlus
145. Shaya FT, Samant N, Skolasky R et al. Modeling risk of gastrointestinal events among Medicaid NSAID users using propensity scores. Expert Rev Pharmacoeconomics Outcomes Res. 2005; 5:625-32.
146. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296; 1633-44. http://www.ncbi.nlm.nih.gov/pubmed/16968831?dopt=AbstractPlus
147. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332; 1302-5. http://www.ncbi.nlm.nih.gov/pubmed/16740558?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1473048&blobtype=pdf
148. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006; 296:1653-6. http://www.ncbi.nlm.nih.gov/pubmed/16968830?dopt=AbstractPlus
149. Bertagnolli MM, Eagle CJ, Zauber A et al., for the APC study investigators. Celecoxib for the prevention of sporadic colorectal adenomas. N Eng J Med. 2006; 355:873-84. http://www.ncbi.nlm.nih.gov/pubmed/16943400?dopt=AbstractPlus
150. Arber N, Eagle CJ, Spicak J, et al., for the PreSAP trial investigators. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006; 355; 885-95. http://www.ncbi.nlm.nih.gov/pubmed/16943401?dopt=AbstractPlus
151. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: http://www.effectivehealthcare.ahrq.gov/synthesize/reports/final.cfm.
152. Solomon SD, Pfeffer MA, McMurray JJV, et al., for the APC and PreSAP trial investigators. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation. 2006; 114: 1028-35. http://www.ncbi.nlm.nih.gov/pubmed/16943394?dopt=AbstractPlus
153. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.
154. Boulos P, Dougados M, MacLeod SM et al. Pharmacological treatment of ankylosing spondylitis. A systematic review. Drugs. 2005; 65:2111-27. http://www.ncbi.nlm.nih.gov/pubmed/16225367?dopt=AbstractPlus
155. Zochling Z, van der Heijde D, Braun J et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis. 2006; 65:423-32. http://www.ncbi.nlm.nih.gov/pubmed/16126792?dopt=AbstractPlus
156. Zochling Z, van der Heijde D, Burgos-Vargas R et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2006; 65:442-52. http://www.ncbi.nlm.nih.gov/pubmed/16126791?dopt=AbstractPlus
157. Gislason GH, Jacobsen S, Rasmussen JN et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006; 113:2906-13. http://www.ncbi.nlm.nih.gov/pubmed/16785336?dopt=AbstractPlus
158. Andersohn F, Suissa A, Garbe E. Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation. 2006; 113:1950-57. http://www.ncbi.nlm.nih.gov/pubmed/16618816?dopt=AbstractPlus
159. Giannini EH, Ruperto N, Ravelli A et al. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum. 1997; 40:1202-9. http://www.ncbi.nlm.nih.gov/pubmed/9214419?dopt=AbstractPlus
160. Ilowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics. 2002; 109:109-115. http://www.ncbi.nlm.nih.gov/pubmed/11773549?dopt=AbstractPlus
500. Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD; 2015 Jul 9. From the FDA web site. Accessed 2016 Mar 22. http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm
501. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382:769-79. http://www.ncbi.nlm.nih.gov/pubmed/23726390?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3778977&blobtype=pdf
502. Food and Drug Administration. FDA briefing document: Joint meeting of the arthritis advisory committee and the drug safety and risk management advisory committee, February 10-11, 2014. From FDA web site http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM383180.pdf
503. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011; 342:c7086. http://www.ncbi.nlm.nih.gov/pubmed/21224324?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3019238&blobtype=pdf
504. Gislason GH, Rasmussen JN, Abildstrom SZ et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009; 169:141-9. http://www.ncbi.nlm.nih.gov/pubmed/19171810?dopt=AbstractPlus
505. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011; 123:2226-35. http://www.ncbi.nlm.nih.gov/pubmed/21555710?dopt=AbstractPlus
506. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8:e1001098. http://www.ncbi.nlm.nih.gov/pubmed/21980265?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3181230&blobtype=pdf
507. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 62:e147-239. http://www.ncbi.nlm.nih.gov/pubmed/23747642?dopt=AbstractPlus
508. Pfizer. Celebrex (celecoxib capsules) prescribing information. New York, NY; 2016 May.
510. Helin-Salmivaara A, Virtanen A, Vesalainen R et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006; 27:1657-63. http://www.ncbi.nlm.nih.gov/pubmed/16731535?dopt=AbstractPlus
511. Olsen AM, Fosbøl EL, Lindhardsen J et al. Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study. Circulation. 2012; 126:1955-63. http://www.ncbi.nlm.nih.gov/pubmed/22965337?dopt=AbstractPlus
512. Olsen AM, Fosbøl EL, Lindhardsen J et al. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study. PLoS One. 2013; 8:e54309.
513. Combe B, Swergold G, McLay J et al. Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study). Rheumatology (Oxford). 2009; 48:425-32. http://www.ncbi.nlm.nih.gov/pubmed/19223284?dopt=AbstractPlus
514. Baron JA, Sandler RS, Bresalier RS et al. Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008; 372:1756-64. http://www.ncbi.nlm.nih.gov/pubmed/18922570?dopt=AbstractPlus
515. ADAPT Research Group. Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT). PLoS Clin Trials. 2006; 1:e33. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1851724&blobtype=pdf
516. Bavry AA, Khaliq A, Gong Y et al. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med. 2011; 124:614-20. http://www.ncbi.nlm.nih.gov/pubmed/21596367?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4664475&blobtype=pdf
517. Kohli P, Steg PG, Cannon CP et al. NSAID use and association with cardiovascular outcomes in outpatients with stable atherothrombotic disease. Am J Med. 2014; 127:53-60.e1. http://www.ncbi.nlm.nih.gov/pubmed/24280110?dopt=AbstractPlus
518. Solomon SD, Wittes J, Finn PV et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008; 117:2104-13. http://www.ncbi.nlm.nih.gov/pubmed/18378608?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2965408&blobtype=pdf
519. Brune K, Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs. J Pain Res. 2015; 8:105-18. http://www.ncbi.nlm.nih.gov/pubmed/25759598?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4346004&blobtype=pdf
More about celecoxib
- Side Effects
- During Pregnancy or Breastfeeding
- Dosage Information
- Patient Tips
- Drug Images
- Drug Interactions
- Compare Alternatives
- Pricing & Coupons
- En Español
- 217 Reviews
- Drug class: cox-2 inhibitors
- FDA Alerts (3)