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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Celebrex® may be confused with Celexa®, cerebra, Cerebyx®
Pronunciation
(se le KOKS ib)
U.S. Brand Names
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Relief of the signs and symptoms of osteoarthritis, ankylosing spondylitis, juvenile rheumatoid arthritis (JRA), and rheumatoid arthritis; management of acute pain; treatment of primary dysmenorrhea; to reduce the number of intestinal polyps in familial adenomatous polyposis (FAP)
Canadian note: Celecoxib is only indicated for relief of symptoms of rheumatoid arthritis, osteoarthritis, and relief of acute pain in adults
Use: Dental
Management of acute dental pain
Restrictions
An FDA-approved medication guide must be distributed when dispensing an oral outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
Pregnancy Risk Factor
C/D (3rd trimester)
Pregnancy Considerations
Teratogenic effects were observed in animal studies. Avoid use in the 3rd trimester of pregnancy, this drug may cause premature closure of the ductus arteriosus.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Based on limited data, celecoxib has been found to be excreted in milk; a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Contraindications
Hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass surgery (CABG); pregnancy (3rd trimester)
Canadian labeling: Additional contraindications (not in U.S. labeling): Pregnancy (3rd trimester); women who are breast-feeding; severe, uncontrolled heart failure; active gastrointestinal ulcer (gastric, duodenal, peptic) or bleeding; inflammatory bowel disease; cerebrovascular bleeding; severe liver impairment or active hepatic disease; severe renal impairment (Clcr <30 mL/minute) or deteriorating renal disease; known hyperkalemia; use in children
Warnings/Precautions
Boxed warnings:
• Cardiovascular events: See “Concerns related to adverse effects” below.
• Coronary artery bypass surgery: See “Disease-related concerns” below.
• Gastrointestinal events: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Anaphylactoid reactions: Even in patients without prior exposure, anaphylactic reactions and angioedema may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular events, including MI, stroke, and new onset or worsening of pre-existing hypertension. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. May cause sodium and fluid retention, use with caution in patients with heart failure, edema or hypertension. Long-term cardiovascular risk in children has not been evaluated. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular; alternate therapies should be considered for patients at high risk.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk.
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of rash.
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
• Coronary artery bypass surgery: [U.S. Boxed Warning]: Celecoxib is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass surgery (CABG). Risk of MI and stroke may be increased with use following CABG surgery.
• Cytochrome P450 isoenzyme 2C9 deficiency: Use with caution in patients with known or suspected deficiency of cytochrome P450 isoenzyme 2C9; poor metabolizers may have higher plasma levels due to reduced metabolism.
• Familial adenomatous polyposis (FAP): When used for the treatment of FAP, routine monitoring and care should be continued.
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment; dosage adjustment recommended. Not recommended for patients with severe hepatic impairment. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, jaundice, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.
• Renal impairment: NSAID use may compromise existing renal function. Dose-dependent decreases in prostaglandin synthesis may result from NSAID use, causing a reduction in renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics and ACEI, and the elderly are at greater risk for renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Pediatrics: When used for JRA, celecoxib is not FDA-approved in children <2 years of age or in children <10 kg. Use caution with systemic-onset JRA (may be at risk for disseminated intravascular coagulation). Safety and efficacy have not been established for use in children for indications other than JRA.
Adverse Reactions
>10%:
Cardiovascular: Hypertension (?13%)
Central nervous system: Headache (10% to 16%)
Gastrointestinal: Diarrhea (4% to 11%)
2% to 10%:
Cardiovascular: Peripheral edema (2%)
Central nervous system: Fever (?9%), insomnia (2%), dizziness (1% to 2%)
Dermatologic: Skin rash (2%)
Gastrointestinal: Dyspepsia (9%), nausea (4% to 7%), gastroesophageal reflux (?5%), abdominal pain (4% to 8%), vomiting (?6%), flatulence (2%)
Neuromuscular & skeletal: Arthralgia (?7%), back pain (3%)
Respiratory: Upper respiratory tract infection (8%), cough (?7%), nasopharyngitis (?6%), sinusitis (5%), dyspnea (?3%), pharyngitis (2%), rhinitis (2%)
Miscellaneous: Accidental injury (3%)
0.1% to 2%:
Cardiovascular: Angina, aortic valve incompetence, chest pain, coronary artery disorder, DVT, edema, facial edema, hypertension (aggravated), MI, palpitation, sinus bradycardia, tachycardia, ventricular hypertrophy
Central nervous system: Anxiety, cerebral infarction, depression, fatigue, hypoesthesia, migraine, nervousness, pain, somnolence, vertigo
Dermatologic: Alopecia, bruising, cellulitis, dermatitis, dry skin, nail disorder, photosensitivity, pruritus, rash (erythematous), rash (maculopapular), urticaria
Endocrine & metabolic: Breast fibroadenosis, breast neoplasm, breast pain, diabetes mellitus, dysmenorrhea, hot flashes, hypercholesterolemia, hyperglycemia, hyper-/hypokalemia, hypernatremia, menstrual disturbances, ovarian cyst, testosterone decreased
Gastrointestinal: Anorexia, appetite increased, constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastrointestinal ulcer, hemorrhoids, hiatal hernia, melena, stomatitis, taste disturbance, tenesmus, tooth disorder, weight gain, xerostomia
Genitourinary: Cystitis, dysuria, incontinence, monilial vaginitis, prostate disorder, urinary frequency, urinary tract infection, vaginal bleeding, vaginitis
Hematologic: Anemia, thrombocytopenia
Hepatic: Alkaline phosphatase increased, transaminases increased
Neuromuscular & skeletal: Arthrosis, bone disorder, CPK increased, fracture, leg cramps, myalgia, neck stiffness, neuralgia, neuropathy, paresthesia, hypertonia, synovitis, tendon rupture, tendonitis, weakness
Ocular: Blurred vision, cataract, conjunctival hemorrhage, conjunctivitis, eye pain, glaucoma, vitreous floaters
Otic: Deafness, earache, labyrinthitis, otitis media, tinnitus
Renal: Albuminuria, BUN increased, creatinine increased, hematuria, nonprotein nitrogen increased, renal calculi
Respiratory: Bronchitis, bronchospasm, epistaxis, laryngitis, pneumonia
Miscellaneous: Allergic reactions, allergy aggravated, diaphoresis, flu-like syndrome, herpes infection, infection (bacterial, fungal, viral), moniliasis
<0.1% (Limited to important or life-threatening): Acute renal failure, ataxia, cerebrovascular accident, CHF, cholelithiasis, colitis, esophageal perforation, gangrene, gastrointestinal bleeding, ileus, intestinal obstruction, intestinal perforation, pancreatitis, pulmonary embolism, sepsis, sudden death, suicide, syncope, thrombophlebitis, ventricular fibrillation
Postmarketing and/or case reports: Agranulocytosis, anaphylactoid reactions, angioedema, aplastic anemia, aseptic meningitis, erythema multiforme, exfoliative dermatitis, hepatic failure, hepatic necrosis, hepatitis (including fulminant), hypoglycemia, hyponatremia, interstitial nephritis, intracranial hemorrhage, jaundice, leukopenia, pancytopenia, renal papillary necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis
Metabolism/Transport Effects
Substrate of CYP2C9 (major), 3A4 (minor); Inhibits CYP2C8 (moderate), 2D6 (weak)
Drug Interactions
ACE Inhibitors: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease golmerular filtration and renal function. Risk C: Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy
Antiplatelet Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy
Coumarin Derivatives: NSAID (COX-2 Inhibitor) may enhance the anticoagulant effect of Coumarin Derivatives. Risk C: Monitor therapy
CycloSPORINE: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
CYP2C8 Substrates (High risk with Highly Effective Inhibitors): CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates (High risk with Highly Effective Inhibitors). Risk C: Monitor therapy
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inducers). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inhibitors). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inhibitors). Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk D: Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk D: Consider therapy modification
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Vancomycin. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (increased GI irritation).
Food: Peak concentrations are delayed and AUC is increased by 10% to 20% when taken with a high-fat meal.
Herb/Nutraceutical: Avoid concomitant use with herbs possessing anticoagulation/antiplatelet properties, including alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, Siberian), grapeseed, green tea, guggul, horse chestnuts, horseradish, licorice, prickly ash, red clover, reishi, SAMe (S-adenosylmethionine), sweet clover, turmeric, white willow.
Storage
Store at controlled room temperature of 25°C (77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors. Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations. Celecoxib does not affect platelet aggregation. In FAP, celecoxib reduces the number of colorectal polyps.
Pharmacodynamics/Kinetics
Distribution: Vd (apparent): ~400 L
Protein binding: ~97% primarily to albumin
Metabolism: Hepatic via CYP2C9; forms inactive metabolites
Bioavailability: Absolute: Unknown
Half-life elimination: ~11 hours (fasted)
Time to peak: ~3 hours
Excretion: Feces (57% as metabolites, <3% as unchanged drug); urine (27% as metabolites, <3% as unchanged drug)
Dosage
Note: Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals. Oral:
Children ?2 years: JRA
?10 kg to ?25 kg: 50 mg twice daily
>25 kg: 100 mg twice daily
Adults:
Acute pain or primary dysmenorrhea: Initial dose: 400 mg, followed by an additional 200 mg if needed on day 1; maintenance dose: 200 mg twice daily as needed
Ankylosing spondylitis: 200 mg/day as a single dose or in divided doses twice daily; if no effect after 6 weeks, may increase to 400 mg/day. If no response following 6 weeks of treatment with 400 mg/day, consider discontinuation and alternative treatment.
Familial adenomatous polyposis: 400 mg twice daily
Osteoarthritis: 200 mg/day as a single dose or in divided dose twice daily
Rheumatoid arthritis: 100-200 mg twice daily
Elderly: No specific adjustment based on age is recommended. However, the AUC in elderly patients may be increased by 50% as compared to younger subjects. Initiate at the lowest recommended dose in patients weighing <50 kg.
Dosing adjustment in renal impairment: No specific dosage adjustment is recommended; not recommended in patients with severe renal dysfunction
Dosing adjustment in hepatic impairment: Reduced dosage is recommended (AUC may be increased by 40% to 180%); decrease dose by 50% in patients with moderate hepatic impairment (Child-Pugh class B). Not recommended for use with severe impairment.
Dental Usual Dosing
Acute dental pain: Adults: Oral: 400 mg, followed by an additional 200 mg if needed on day 1; maintenance dose: 200 mg twice daily as needed
Administration: Oral
Lower doses (200 mg twice daily) may be taken without regard to meals. Larger doses should be taken with food to improve absorption. Capsules may be swallowed whole or the entire contents emptied onto a teaspoon of cool or room temperature applesauce. The contents of the capsules sprinkled onto applesauce may be stored under refrigeration for up to 6 hours.
Monitoring Parameters
CBC; blood chemistry profile; occult blood loss and periodic liver function tests; monitor renal function (urine output, serum BUN and creatinine; monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation; observe for weight gain, edema; observe for bleeding, bruising; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia); blood pressure
FAP: Continue routine endoscopic exams
JRA: Monitor for development of abnormal coagulation tests with systemic onset JRA
Dietary Considerations
Lower doses (200 mg twice daily) may be taken without regard to meals. Larger doses should be taken with food to improve absorption.
Patient Education
Do not take more than recommended dose. May be taken with food to reduce GI upset. Do not take with antacids. Avoid alcohol, aspirin, and OTC medication unless approved by prescriber. You may experience dizziness, confusion, or blurred vision (avoid driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, taste disturbance, gastric distress (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain. It is unclear whether celecoxib has rates of these events which are similar to nonselective NSAIDs. Stop taking medication and report immediately stomach pain or cramping; unusual bleeding or bruising (blood in vomitus, stool, or urine); chest pain; shortness of breath; weakness of extremities; or slurring of speech. Report persistent insomnia; skin rash; unusual fatigue or flu-like symptoms; jaundice; muscle pain, tremors, or weakness; sudden weight gain or edema; changes in hearing (ringing in ears) or vision; changes in urination pattern; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform your prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Breast-feeding is not recommended.
Geriatric Considerations
The elderly are at increased risk for adverse effects from NSAIDs. As many as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically; however, elderly patients may demonstrate these adverse effects at lower doses than younger adults. The elderly are also at increased risk of renal toxicity. Although celecoxib is associated with a decreased incidence of GI side effects, use the lowest recommended dose in patients weighing <50 kg.
Anesthesia and Critical Care Concerns/Other Considerations
Celecoxib does not inhibit platelets or prolong bleeding time.
Cardiovascular Considerations
Pfizer, Inc, the manufacturer of Celebrex® (celecoxib) has reported an increased risk of cardiovascular events in one clinical trial during an interim analysis. The increased risk was observed in a trial evaluating celecoxib in patients at risk of colon cancer, prompting the National Cancer Institute to end the study. Further analysis of risk factors related to cardiovascular risk appears warranted.
The FDA further notes that these new findings for celecoxib are similar to results with other drugs in this class. Increased cardiovascular risk noted in a study of rofecoxib (Vioxx®) led to a voluntary withdrawal of the product by Merck. In addition, another drug in this class, valdecoxib (Bextra®) demonstrated an increased risk for cardiovascular events in patients following cardiovascular surgery.
Physicians are encouraged to carefully evaluate individual cardiovascular risk profiles prior to prescribing COX-2 inhibitors. COX-2 inhibitors may be appropriate for patients who do not tolerate nonselective NSAIDs, those who are not doing well on NSAIDs, or those with a history of gastrointestinal bleeding. COX-2 inhibitors may not be appropriate in patients with cardiovascular disease or in patients with significant risk factors for cardiovascular disease. If physicians determine that continued use is appropriate for individual patients, the lowest effective dose of celecoxib should be prescribed for the shortest duration of treatment based upon goals.
Medication guides will be required for all prescription products.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis, abnormal taste, xerostomia (normal salivary flow resumes upon discontinuation), and tooth disorder. Nonselective NSAIDs are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. According to the manufacturer, celecoxib, at single doses up to 800 mg and multiple doses of 600 mg twice daily, had no effect on platelet aggregation or bleeding time. Comparative NSAIDs (naproxen 500 mg twice daily, ibuprofen 800 mg three times daily, or diclofenac 75 mg twice daily) significantly reduced platelet aggregation and prolonged the bleeding times. See Dental Comment.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
The Food and Drug Administration (FDA) has announced product labeling changes for all NSAIDs, including COX-2 selective and over-the-counter (OTC) medications. These changes are the result of the Arthritis and Drug Safety and Risk Management Advisory Committee meeting held in February, 2005.
The FDA has asked that all labels be revised to include information related to the potential for increased risk of cardiovascular (CV) events and gastrointestinal (GI) bleeding associated with their use. In addition, prescription nonselective NSAIDs are being asked to add a contraindication for use in patients who have recently undergone coronary artery bypass graft (CABG) surgery and a boxed warning concerning the CV and GI events. Medication guides will be required for all prescription products. Manufacturers of OTC products are being asked to include a warning about potential skin reactions, which is already included in prescription labeling. The FDA will be working with manufacturers to conduct long-term clinical trials to assess the safety of these agents.
Pfizer, Inc, the manufacturer of celecoxib (Celebrex®) has reported an increased risk of cardiovascular events in one clinical trial during an interim analysis. The increased risk was observed in a trial evaluating celecoxib in patients at risk of colon cancer, prompting the National Cancer Institute to end the study. Other similar clinical studies (which were subjected to analysis by data monitoring committees) are continuing, since an interim analysis of these trials did not reveal an increased risk of cardiovascular events. Further analysis of risk factors related to cardiovascular risk appear warranted. A notice posted by the Food and Drug Administration (FDA) states that the agency “will obtain all available data on these and other ongoing Celebrex® trials as soon as possible and will determine the appropriate regulatory action.”
The FDA further notes that these new findings for celecoxib are similar to results with other drugs in this class. Increased cardiovascular risk noted in a study of rofecoxib (Vioxx®) led to a voluntary withdrawal of the product by Merck. In addition, another drug in this class, valdecoxib (Bextra®) demonstrated an increased risk for cardiovascular events in patients following cardiovascular surgery. Valdecoxib (Bextra®) was withdrawn from the market in May 2005.
In their statement, the FDA encourages physicians to consider this developing information in risk-to-benefit evaluations as they consider the use of celecoxib in individual patients. In addition, the FDA advises an evaluation of alternative therapy. If physicians determine that continued use is appropriate for individual patients, the lowest effective dose of celecoxib should be prescribed. Pfizer has not announced a decision to withdraw celecoxib from the market as of December 20, 2004.
The association between selective COX-2 inhibitors and increased cardiovascular risk has been noted previously and prompted by publication of a meta-analysis entitled “Risk of Cardiovascular Events Associated With Selective COX-2 Inhibitors” in the August 22, 2001, edition of the Journal of the American Medical Association (JAMA). The researchers reanalyzed four previously published trials, assessing cardiovascular events in patients receiving either celecoxib or rofecoxib. They found an association between the use of COX-2 inhibitors and cardiovascular events (including MI and ischemic stroke). The annualized MI rate was found to be significantly higher in patients receiving celecoxib or rofecoxib than in the control (placebo) group from a recent meta-analysis of primary prevention trials. Although cause and effect cannot be established (these trials were originally designed to assess GI effects, not cardiovascular ones), the authors believe the available data raise a cautionary flag concerning the risk of cardiovascular events with the use of COX-2 inhibitors. The manufacturers of these agents, as well as other healthcare professionals, dispute the methods and validity of the study's conclusions. To date, the FDA has not required any change in the labeling of these agents. Further study is required before any potential risk may be defined.
Cross-reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in aspirin-sensitive patients. The manufacturer suggests that celecoxib should not be administered to patients with this type of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.
The manufacturer studied the effect of celecoxib on the anticoagulant effect of warfarin and found no alteration of anticoagulant effect, as determined by prothrombin time, in patients taking 2 mg to 5 mg daily. However, the manufacturer has issued a caution when using celecoxib with warfarin since those patients are at increased risk of bleeding complications.
Mental Health: Effects on Mental Status
May cause dizziness and insomnia; may rarely, cause anxiety, depression, nervousness, or somnolence
Mental Health: Effects on Psychiatric Treatment
Effects of benzodiazepines and antidepressants may be altered. Lithium concentrations may be increased by celecoxib via decreased renal lithium clearance; dose adjustment may be needed.
Nursing: Physical Assessment/Monitoring
Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Assess effectiveness and interactions of other medications patient may be taking (ie, monitor patients taking lithium closely). Assess allergy history (aspirin, NSAIDs, salicylates). Monitor blood pressure at the beginning of therapy and periodically during use. Monitor effectiveness of therapy. Assess knowledge/teach patient appropriate use, possible side effects/interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Celebrex®: 50 mg, 100 mg, 200 mg, 400 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Celebrex)
100 mg (30): $75.99
200 mg (30): $120.91
400 mg (30): $176.00
References
Arbor N, Eagle CJ, Spicak J, et al, “Celecoxib for the Prevention of Colorectal Adenomatous Polyps,” N Engl J Med, 2006, 355(9):885-95.
Bertagnolli MM, Eagle CJ, Zauber AG, et al, “Celecoxib for the Prevention of Sporadic Colorectal Adenomas,” N Engl J Med, 2006, 355(9):873-84.
Geis GS, et al, “Efficacy and Safety of Celecoxib, A Specific COX-2 Inhibitor, in Patients With Rheumatoid Arthritis,” Arthritis Rheum, 1998, 41(9 Suppl):316:1699.
Karim A, et al, “Celecoxib, a Specific COX-2 Inhibitor, Lacks Significant Drug-Drug Interactions With Methotrexate or Warfarin,” Arthritis Rheum, 1998, 41(9 Suppl):315:1698.
Lane NE, “Pain Management in Osteoarthritis: The Role of COX-2 Inhibitors,” J Rheumatol, 1997, 24(Suppl 49):20-4.
Lipsky PE and Isakson PC, “Outcome of Specific COX-2 Inhibition in Rheumatoid Arthritis,” J Rheumatol, 1997, 24(Suppl 49):9-14.
Mengle-Gaw L, et al, “A Study of the Platelet Effects of SC-58635, A Novel COX-2 Selective Inhibitor,” Arthritis Rheum, 1998, 41(9 Suppl):93-374.
Needleman P and Isakson PC, “The Discovery and Function of COX-2,” J Rheumatol, 1997, 24(Suppl 49):6-8.
Nussmeier NA, Whelton AA, Brown MT, et al, “Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib After Cardiac Surgery,” N Engl J Med, 2005, 352(11):1081-91.
Simon LS, et al, “Preliminary Study of the Safety and Efficacy of SC-58635, a Novel Cyclo-oxygenase 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.
Solomon SD, McMurray JJ, Pfeffer MA, et al, “Cardiovascular Risk Associated With Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention,” N Engl J Med, 2005, 352(11):1071-80.
Steinbach G, Lynch PM, Phillips RK, et al, “The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor, in Familial Adenomatous Polyposis,” N Engl J Med, 2000, 342(26):1946-52.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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