Generic Name: Celecoxib
Class: Cyclooxygenase-2 (COX-2) Inhibitors
Chemical Name: 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
CAS Number: 184007-95-2
- Cardiovascular Risk
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.1
- GI Risk
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)
Introduction
NSAIA1 2 3 4 5 8 11 41 that is a selective inhibitor of cycloogenase-2 (COX-2);1 2 8 diaryl-substituted pyrazole derivative containing a sulfonamide substituent.1 2 3 4 5 8 11 41
Uses for Celebrex
Consider potential benefits and risks of celecoxib therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.1
Osteoarthritis
Symptomatic treatment of osteoarthritis.1 2 3 28 29 64 Effect comparable to that of prototypical NSAIAs (naproxen).1 2 3 28 29 64
Lower incidence of endoscopically confirmed GI ulcer and serious adverse GI effects than prototypical NSAIAs.1 28 29 33 79
Rheumatoid Arthritis in Adults
Symptomatic treatment of rheumatoid arthritis in adults.1 2 3 9 10 21 23 24 28 65 66 99 Effect comparable to that of prototypical NSAIAs (naproxen, diclofenac).1 2 3 9 10 21 23 24 28 65 66 99
Lower incidence of endoscopically confirmed GI ulcer and serious adverse GI effects than prototypical NSAIAs.1 3 9 10 21 23 24 28 33 65 66 79
Juvenile Arthritis
Symptomatic management of pauciarticular course, polyarticular course, or systemic onset juvenile rheumatoid arthritis in children ≥2 years of age.1 Effect comparable to that of naproxen.1
Ankylosing Spondylitis
Management of the signs and symptoms of ankylosing spondylitis.1 132
Colorectal Polyps
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
Pain
Management of acute pain, including postoperative (e.g., dental, orthopedic) pain, in adults.1 8 42 43
Dysmenorrhea
Symptomatic management of primary dysmenorrhea in adults.1 2
Cardiovascular Risk Reduction
Not a substitute for aspirin in the prevention of adverse cardiovascular events (MI).1 (See Cardiovascular Effects under Cautions.)
Celebrex Dosage and Administration
General
Administration
Oral Administration
Administer orally once or twice daily for osteoarthritis or ankylosing spondylitis; administer twice daily for rheumatoid arthritis, juvenile arthritis, colorectal polyps, pain, or dysmenorrhea.1 2
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
Dosage
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
Pediatric Patients
Juvenile Arthritis
Oral
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
Adults
Osteoarthritis
Oral
200 mg daily as a single dose or in 2 equally divided doses.1 2 3
No additional benefit from dosages >200 mg daily.1
Rheumatoid Arthritis in Adults
Oral
100–200 mg twice daily.1 78
No additional benefit from higher dosages (400 mg twice daily).1
Ankylosing Spondylitis
Oral
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
Colorectal Polyps
Oral
400 mg twice daily.1 60
Pain
Oral
400 mg initially as a single dose, followed by an additional dose of 200 mg, if necessary, on the first day.1 For continued relief, 200 mg twice daily as needed.1
Dysmenorrhea
Oral
400 mg initially as a single dose, followed by an additional dose of 200 mg, if necessary, on the first day.1 For continued relief, 200 mg twice daily as needed.1
Special Populations
Hepatic Impairment
Reduce dosage by 50% in patients with moderate hepatic impairment; not recommended in patients with severe impairment.1
Geriatric Patients
Dosage adjustment based solely on age is not necessary; initiate at lowest recommended dosage in geriatric patients weighing <50 kg.1
Cautions for Celebrex
Contraindications
Known hypersensitivity to celecoxib, sulfonamides, or any ingredient in the formulation.1
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1
Treatment of perioperative pain in the setting of CABG surgery.1
Warnings/Precautions
Warnings
Cardiovascular Effects
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.1 103 104 113 116 122 123 129 130 131 134 137 138 139 140 141 146 147 148 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.146 147 148 Current evidence suggests that use of celecoxib at dosages >200 mg daily is associated with increased cardiovascular risk, while the potential risk is less clear at dosages of ≤200 mg daily.146 148 157 158
Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).133
Not known whether long-term use in children is associated with increased cardiovascular risk.1
Use celecoxib with caution and careful monitoring (e.g., monitor for development of cardiovascular events).1 102 112 Until more data are available, a selective COX-2 inhibitor remains an appropriate choice for patients at low cardiovascular risk who have had serious GI events, especially while receiving a prototypical NSAIA.112 121 128 145 May be prudent to avoid use of selective COX-2 inhibitors in patients who have or are at risk for cardiovascular disease.112 121 124 128 142 143
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 103 133 134 135 139 141 (See Specific Drugs under Interactions.)
Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)
Fluid retention and edema reported.1 Caution in patients with fluid retention or heart failure.1
GI Effects
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
Lower risk of GI ulceration than prototypical NSAIAs.1 2 3 9 21 22 24 28 29 33 38 65 66
Renal Effects
Adverse renal effects similar to those of prototypical NSAIAs.1 2 58 59
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.)
FAP
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
Sensitivity Reactions
Hypersensitivity Reactions
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
Dermatologic Reactions
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
General Precautions
Hepatic Effects
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
Hematologic Effects
Anemia reported rarely.1 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia 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
CYP2D6 Phenotype
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
Other Precautions
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
Specific Populations
Pregnancy
Category C.1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1
Lactation
Distributed into milk in rats; not known whether distributed into milk in humans.1 Discontinue nursing or the drug.1
Pediatric Use
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
Geriatric Use
Efficacy similar to that in younger adults.1 However, fatal adverse GI effects and acute renal failure reported more frequently in geriatric patients than younger adults.1
Hepatic Impairment
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.)
Renal Impairment
Use with caution in patients with renal disease.1 No experience in patients with advanced renal disease; use not recommended in such patients; close monitoring of renal function advised if used.1
Common Adverse Effects
Adults: Abdominal pain, diarrhea, dyspepsia, headache, nausea, sinusitis, upper respiratory tract infection.1
Children: Headache, fever, abdominal pain, cough, nasopharyngitis, nausea, arthralgia, diarrhea, vomiting.1
Interactions for Celebrex
Metabolized by CYP2C9.77
Inhibits CYP2D6; does not inhibit CYP2C9, CYP2C19, or CYP3A4.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Potential pharmacokinetic interaction (increased plasma celecoxib concentrations) with drugs that inhibit CYP2C9.1 Caution is advised.1
Potential pharmacokinetic interaction (increased plasma concentrations of CYP2D6 substrate) with drugs metabolized by CYP2D6.1 3 6 44
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
ACE inhibitors
|
Reduced BP response to ACE inhibitor1
|
Monitor BP1
|
Angiotensin II receptor antagonists
|
Reduced BP response to angiotensin II receptor antagonists153
|
Monitor BP153
|
Antacids (magnesium- or aluminum-containing)
|
Decreased plasma concentration and AUC of celecoxib1 50
|
Not considered clinically important1 50
|
Aspirin
|
Increased risk of GI ulceration and other complications1 33 79
No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs1 103 133 134 139 141
|
|
Diuretics (furosemide, thiazides)
|
Reduced natriuretic effects1
|
|
Fluconazole
|
Increased plasma celecoxib concentrations1
|
Initiate celecoxib at lowest recommended dosage1
|
Glyburide
|
Pharmacokinetic interaction unlikely1
|
|
Ketoconazole
|
Pharmacokinetic interaction unlikely1
|
|
Lithium
|
Increased plasma lithium concentrations1
|
Monitor for lithium toxicity when initiating or discontinuing celecoxib1
|
Methotrexate
|
Pharmacokinetics of methotrexate not altered1
|
|
Phenytoin
|
Pharmacokinetic interaction unlikely1
|
|
Tolbutamide
|
Pharmacokinetic interaction unlikely1
|
|
Warfarin
|
Reports of bleeding complications and increases in PT in some (mainly geriatric) patients1 56 57
|
Monitor anticoagulant activity, especially when initiating or changing celecoxib therapy1 56 57
|
Celebrex Pharmacokinetics
Absorption
Bioavailability
Well absorbed following oral administration; peak plasma concentration usually attained within 3 hours in fasting individuals.1 2 23
Onset
Single doses provide pain relief within 60 minutes.1
Food
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
Special Populations
In geriatric patients, peak plasma concentration and AUC increased by 40 and 50%, respectively.1 2
In patients with mild or moderate hepatic impairment, AUC increased by 40 or 180%, respectively.1 2
In patients with chronic renal impairment (GFR 35–60 mL/minute), AUC decreased by 40%; pharmacokinetics not studied in patients with severe renal impairment.1 2
Distribution
Extent
Not well characterized.1
Plasma Protein Binding
97% (principally albumin; α1-acid glycoprotein to a lesser extent).1 2 23
Elimination
Metabolism
Metabolized in the liver to inactive metabolites, mainly by CYP2C9.1 2 23
Elimination Route
Excreted in urine and feces principally as metabolites.1 2 23
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
Half-life
11 hours under fasting conditions.1
Stability
Storage
Oral
Capsules
25°C (may be exposed to 15–30°C).1
Mixture of capsule contents in applesauce is stable for 6 hours when refrigerated.1
ActionsActions
Selective inhibitor of COX-2.1 2 3 4 5 7 8 10 48 52 53
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
Anti-inflammatory, analgesic, and antipyretic actions; no effect on platelets at usual therapeutic doses; may reduce risk of colon cancer.1 2 3 9 15 20 38 53 60 61 75 76 77
Lower risk of GI ulceration than prototypical NSAIAs.1 2 3 9 21 22 24 28 29 33 38 65 66
Advice to Patients
Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1
Risk of serious cardiovascular events with long-term use.1
Risk of GI bleeding and ulceration.1
Risk of serious skin reactions.1 Risk of anaphylactoid and other sensitivity reactions.1
Risk of hepatotoxicity.1
Not a substitute for aspirin in the prevention of adverse cardiovascular events.1
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1
Importance of discontinuing celecoxib and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of avoiding celecoxib use in late pregnancy (third trimester).1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
For patients with FAP, importance of continuing usual care.1
Importance of informing patients of other important precautionary information. (See Cautions.)1
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Celecoxib
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Capsules
|
50 mg
|
Celebrex (with povidone)
|
Pfizer
|
|
|
100 mg
|
Celebrex (with povidone)
|
Pfizer
|
|
|
200 mg
|
Celebrex (with povidone)
|
Pfizer
|
|
|
400mg
|
Celebrex (with povidone)
|
Pfizer
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
CeleBREX 100MG Capsules (PFIZER U.S.): 30/$90.99 or 90/$249.97
CeleBREX 200MG Capsules (PFIZER U.S.): 30/$140.99 or 90/$404.97
CeleBREX 400MG Capsules (PFIZER U.S.): 30/$208.98 or 90/$601.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
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