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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(se le KOKS ib)
Generic Available (U.S.)
No
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088567.pdf, must be dispensed with this medication.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Relief of the signs and symptoms of osteoarthritis, ankylosing spondylitis, juvenile idiopathic arthritis (JIA), and rheumatoid arthritis; management of acute pain; treatment of primary dysmenorrhea
Use: Dental
Management of acute dental pain
Pregnancy Risk Factor
C (prior to 30 weeks gestation)/D (≥30 weeks gestation)
Pregnancy Considerations
Teratogenic effects have been observed in some animal studies; therefore, celecoxib is classified as pregnancy category C. Celecoxib is a NSAID that primarily inhibits COX-2 whereas other currently available NSAIDs are nonselective for COX-1 and COX-2. The effects of this selective inhibition to the fetus have not been well studied and limited information is available specific to celecoxib. NSAID exposure during the first trimester is not strongly associated with congenital malformations; however, cardiovascular anomalies and cleft palate have been observed following NSAID exposure in some studies. The use of a NSAID close to conception may be associated with an increased risk of miscarriage. Nonteratogenic effects have been observed following NSAID administration during the third trimester including: Myocardial degenerative changes, prenatal constriction of the ductus arteriosus, fetal tricuspid regurgitation, failure of the ductus arteriosus to close postnatally; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding (including intraventricular hemorrhage), platelet dysfunction with resultant bleeding; pulmonary hypertension. Because it may cause premature closure of the ductus arteriosus, the use of celecoxib is not recommended ≥30 weeks gestation. The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. A registry is available for pregnant women exposed to autoimmune medications including celecoxib. For additional information contact the Organization of Teratology Information Specialists, OTIS Autoimmune Diseases Study, at 877-311-8972.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Small amounts of celecoxib are found in breast milk. The manufacturer recommends that caution be exercised when administering celecoxib to nursing women.
Contraindications
Hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Canadian labeling: Additional contraindications (not in U.S. labeling): Pregnancy (third 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 graft 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 serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. 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. New onset hypertension or exacerbation of hypertension may occur (NSAIDS may impair response to thiazide or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema or heart failure. 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 serious gastrointestinal ulceration, bleeding, and perforation (may be fatal). 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. When used concomitantly with ≤325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
• Hematologic effects: Anemia may occur; monitor hemoglobin or hematocrit in patients on long-term treatment. Celecoxib does not usually affect PT, PTT or platelet counts; does not inhibit platelet aggregation at approved doses.
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning and in patients without prior known sulfa allergy; discontinue use at first sign of rash (or any other hypersensitivity).
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use with caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Celecoxib is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft surgery (CABG). Risk of MI and stroke may be increased with use following CABG surgery.
• Corticosteroid-dependent diseases: Should not be considered a treatment or replacement of corticosteroid-dependent diseases.
• 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; consider reduced initial doses. Alternate therapies should be considered in patients with JIA who are poor metabolizers of CYP2C9.
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment; dosage adjustment recommended. Not recommended for patients with severe hepatic impairment. Transaminase elevations have been reported with use; 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, if systemic manifestations occur, or with persistent or worsening abnormal hepatic function tests.
• 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 (usually reversible). Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors, angiotensin II receptor blockers, 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 or severe renal insufficiency; discontinue use with persistent or worsening abnormal renal function tests. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Pediatrics: When used for juvenile idiopathic arthritis (JIA), celecoxib is not FDA-approved in children <2 years of age or in children <10 kg. Use caution with systemic-onset JIA (may be at risk for disseminated intravascular coagulation). Safety and efficacy have not been established for use in children for indications other than JIA.
Adverse Reactions
≥2%:
Cardiovascular: Peripheral edema
Central nervous system: Dizziness, fever, headache, insomnia
Dermatologic: Rash
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, nausea, vomiting
Neuromuscular & skeletal: Arthralgia, back pain
Respiratory: Cough, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection
0.1% to 1.9%:
Cardiovascular: Angina, aortic valve incompetence, chest pain, coronary artery disorder, edema, facial edema, hypertension (aggravated), MI, palpitation, sinus bradycardia, tachycardia, ventricular hypertrophy
Central nervous system: Anxiety, depression, fatigue, hypoesthesia, migraine, nervousness, pain, somnolence, vertigo
Dermatologic: Alopecia, bruising, cellulitis, dermatitis, dry skin, photosensitivity, pruritus, rash (erythematous), rash (maculopapular), urticaria
Endocrine & metabolic: Hot flashes, hypercholesterolemia, hyperglycemia, hypokalemia, ovarian cyst, testosterone decreased
Gastrointestinal: Anorexia, appetite increased, constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, gastrointestinal ulcer, hemorrhoids, hiatal hernia, melena, stomatitis, tenesmus, weight gain, xerostomia
Genitourinary: Cystitis, dysuria, urinary frequency
Hematologic: Anemia, thrombocythemia
Hepatic: Alkaline phosphatase increased, transaminases increased
Neuromuscular & skeletal: Arthrosis, CPK increased, hypertonia, leg cramps, myalgia, paresthesia, synovitis, tendonitis
Ocular: Conjunctival hemorrhage, vitreous floaters
Otic: Deafness, labyrinthitis, tinnitus
Renal: Albuminuria, BUN increased, creatinine increased, hematuria, nonprotein nitrogen increased, renal calculi
Respiratory: Bronchitis, bronchospasm, dyspnea, epistaxis, laryngitis, pneumonia
Miscellaneous: Allergic reactions, allergy aggravated, cyst, diaphoresis, flu-like syndrome
<0.1%, postmarketing, and/or case reports (limited to important or life-threatening): Acute renal failure, agranulocytosis, anaphylactoid reactions, angioedema, anosmia, aplastic anemia, aseptic meningitis, cerebrovascular accident, CHF, cholelithiasis, colitis, DVT, erythema multiforme, esophageal perforation, exfoliative dermatitis, gangrene, gastrointestinal bleeding, hepatic failure, hepatic necrosis, hepatitis (including fulminant), hypoglycemia, hyponatremia, ileus, interstitial nephritis, intestinal obstruction, intestinal perforation, intracranial hemorrhage, jaundice, leukopenia, pancreatitis, pancytopenia, pulmonary embolism, renal papillary necrosis, sepsis, Stevens-Johnson syndrome, sudden death, suicide, syncope, taste disturbance, thrombocytopenia, thrombophlebitis, toxic epidermal necrolysis, vasculitis, ventricular fibrillation
Metabolism/Transport Effects
Substrate of CYP2C9 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (moderate), CYP2D6 (moderate)
Drug Interactions
ACE Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. 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: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular 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. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. 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
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). 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. CycloSPORINE may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification
CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. Risk C: Monitor therapy
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. 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. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. 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
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Systemic): 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. Management: Monitor for decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concomitant use of these agents in CHF or cirrhosis with ascites. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of CYP2D6 Inhibitors (Moderate). Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). NSAID (COX-2 Inhibitor) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Thrombolytic Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. 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 increase the serum concentration of Vancomycin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (COX-2 Inhibitor) may enhance the anticoagulant effect of Vitamin K Antagonists. 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 25°C (77°F); 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; has antipyretic, analgesic, and anti-inflammatory properties. Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.
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 treatment goals. Oral:
Children ≥2 years: Juvenile idiopathic arthritis (JIA):
≥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.
Canadian labeling: Recommended maximum dose for treatment of acute pain: 400 mg/day up to 7 days
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.
Canadian labeling: Recommended maximum dose: 200 mg/day
Osteoarthritis: 200 mg/day as a single dose or in divided doses 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 poor CYP2C9 metabolizers (eg, CYP2C9*3/*3): Consider reducing initial dose by 50%; consider alternative treatment in patients with JIA who are poor CYP2C9 metabolizers.
Canadian labeling: Recommended maximum dose: 100 mg/day
Dosing adjustment in renal impairment:
Advanced renal disease: Use is not recommended; however, if celecoxib treatment cannot be avoided, monitor renal function closely
Severe renal insufficiency: Use is not recommended.
Canadian labeling: Clcr <30 mL/minute: Use is contraindicated.
Abnormal renal function tests (persistent or worsening): Discontinue use
Dosing adjustment in hepatic impairment:
Moderate hepatic impairment (Child-Pugh class B): Reduce dose by 50%
Severe hepatic impairment (Child-Pugh class C): Use is not recommended
Canadian labeling: Use is contraindicated.
Abnormal liver function tests (persistent or worsening): Discontinue use
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
May be administered without regard to meals. 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; blood pressure (baseline and during treatment); observe for weight gain, edema; observe for bleeding, bruising; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia)
JIA: Monitor for development of abnormal coagulation tests with systemic onset JIA
Dietary Considerations
May be taken without regard to meals.
Patient Education
May be taken with food to reduce GI upset. Avoid alcohol. You may experience dizziness, confusion, blurred vision, anorexia, nausea, vomiting, taste disturbance, or gastric distress; GI bleeding, ulceration, or perforation can occur with or without pain. 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 skin rash, unusual fatigue, flu-like symptoms, jaundice, weakness, sudden weight gain or edema, changes in hearing (ringing in ears) or vision, changes in urination pattern, or respiratory difficulty.
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
Clinical Pearls/Comments: Celecoxib does not inhibit platelets or prolong bleeding time.
Cardiovascular Considerations
An increased risk of cardiovascular events during an interim analysis of one clinical trial has been demonstrated. This trial evaluated use in patients at risk of colon cancer which is now an unapproved use. This information prompted early termination of the study.
These 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. 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 it is determined that continued use is appropriate, the lowest effective dose of celecoxib should be prescribed for the shortest duration of treatment based upon goals.
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.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
The product labeling for all prescription nonsteroidal anti-inflammatory agents (NSAIDs) now include boxed warnings regarding an increased risk of cardiovascular (CV) events and gastrointestinal (GI) bleeding associated with their use and a contraindication for use in patients who have recently undergone coronary artery bypass graft (CABG) surgery. Medication guides are also now required for these products. Manufacturers of over-the-counter products are to include warnings about potential skin reactions, which are already included in prescription labeling.
The FDA encourages physicians to consider this information in risk-to-benefit evaluations while considering the use of the COX-2 selective celecoxib (CeleBREX®) in patients. Similar COX-2 selective drugs, including rofecoxib (Vioxx®) and valdecoxib (Bextra®), were pulled from the market due to increased risks of adverse CV events associated with their use. 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.
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 re-evaluated 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.
Cross-reactivity, including bronchospasm, is a concern with aspirin and other NSAIDs, 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 2-5 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 allergy history (aspirin, NSAIDs, salicylates). Monitor blood pressure at the beginning of therapy and periodically during use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
CeleBREX®: 50 mg, 100 mg, 200 mg, 400 mg
Pricing: U.S. (www.drugstore.com)
Capsules (CeleBREX)
50 mg (30): $49.99
100 mg (30): $90.99
200 mg (30): $142.99
400 mg (30): $208.98
References
Bell AD, Roussin A, Cartier R, et al, “The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” Can J Cardiol, 2011, 27(Suppl A):1-59.
Bhatt DL, Scheiman J, Abraham NS, et al, “ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risk of Antiplatelet Therapy and NSAID Use. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” J Am Coll Cardiol, 2008, 52(18):1502-17.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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