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Celecoxib (Monograph)

Brand name: CeleBREX
Drug class: Cyclooxygenase-2 (COX-2) Inhibitors
- COX-2 Inhibitors

Medically reviewed by Drugs.com on Aug 25, 2023. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for the fixed combination of celecoxib and tramadol hydrochloride under a shared REMS system (Opioid Analgesic REMS) to ensure that the benefits outweigh the risks. The REMS consists of the following: medication guide and elements to assure safe use. See the FDA REMS page [Web]

Warning

    Cardiovascular Risk

  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 500 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.1 508

    GI Risk

  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals and patients with history of peptic ulcer disease and/or GI bleeding 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 cyclooxygenase-2 (COX-2);1 2 8 diaryl-substituted pyrazole derivative containing a sulfonamide substituent.1 2 3 4 5 8 11 41

Uses for Celecoxib

Consider potential benefits and risks of celecoxib therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1

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

Has been used to reduce the number of adenomatous colorectal polyps (colorectal adenomas) in adults with familial adenomatous polyposis† [off-label] (FAP) as an adjunct to usual care.60 162 Previously FDA-labeled for this use; however, approval was granted under FDA's accelerated approval regulations, and a postapproval study was required to verify clinical benefit.169 Labeled indication was withdrawn because patient accrual in the study was slow and manufacturer was unable to provide confirmatory data.169 170 Because celecoxib therapy in patients with FAP has involved high-dose, long-term use, there is concern that potential risks (e.g., GI, cardiovascular) of celecoxib might not be outweighed by the uncertain benefit.170 171

Has been investigated for the prevention of colorectal adenomas in patients without a history of FAP† [off-label].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

Celecoxib/tramadol tablets: Management of acute pain in adults that is severe enough to require an opioid analgesic and for which alternative treatment options (e.g., nonopiate analgesics) have not been, or are not expected to be, adequate or tolerated.172

Migraine

Acute treatment of attacks of migraine with or without aura.161 165 Should not be used for prophylaxis of migraine.161

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 Thrombotic Effects under Cautions.)

Celecoxib 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, pain, or dysmenorrhea.1 2

Capsules

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

Celecoxib/Amlodipine Fixed-combination Tablets

For once-daily administration only.1201

Oral Solution

For acute treatment of migraine attack, administer oral solution without regard to food.161 Patient may drink up to 240 mL of water after administering oral solution.161

When intended dose of the oral solution is less than the entire contents of the single-dose bottle (120 mg in 4.8 mL [25 mg/mL]), use a calibrated measuring device to accurately measure and deliver the dose; discard any remaining solution.161 Consult manufacturer's instructions for use for additional information on administration.161

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

Celecoxib/amlodipine fixed combination: Administer once daily in patients requiring celecoxib for symptomatic treatment of osteoarthritis and amlodipine for management of hypertension.1201 Fixed-combination tablets are available in only one strength of celecoxib (200 mg); do not use in patients requiring lower doses of the drug.1201

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

Fixed-combination of celecoxib and tramadol hydrochloride: 2 tablets (56 mg of celecoxib and 44 mg of tramadol hydrochloride each) every 12 hours as needed.172

Migraine
Acute Treatment
Oral

Single 120-mg dose (as oral solution).161 Efficacy and safety of administering a second dose within a 24-hour period is not established.161 Use on as-needed basis for the fewest possible number of days per month.161

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

Prescribing Limits

Adults

Migraine
Acute Treatment
Oral

Maximum 120 mg per 24-hour period.161

Special Populations

Hepatic Impairment

Moderate hepatic impairment: Reduce dosage by 50%;1 recommended and maximum dosage for acute treatment of migraine attacks is 60 mg.161

Severe hepatic impairment: Use not recommended.1 161

Renal Impairment

Mild or moderate renal impairment: For acute treatment of migraine attacks, no adjustment of usual recommended dosage is required.161 Manufacturer makes no specific recommendations for dosage modification for other indications.1

Severe renal impairment: Use not recommended.1 161 (See Renal Effects and Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustment based solely on age is not necessary; initiate at lowest recommended dosage in geriatric patients weighing <50 kg.1

CYP2C9 Poor or Intermediate Metabolizers

Known or suspected CYP2C9 poor metabolizers with CYP2C9*3/*3 diplotype: Manufacturer recommends reducing initial dosage by 50%.1 Recommended and maximum dosage for acute treatment of migraine attacks is 60 mg.161 (See Elimination: Special Populations, under Pharmacokinetics.)

Manufacturer states consider alternatives to celecoxib for treatment of juvenile rheumatoid arthritis in pediatric patients who are known or suspected CYP2C9 poor metabolizers.1

For CYP2C9 poor metabolizers (i.e., diplotype functional activity score [AS] of 0.5 or 0 [e.g., CYP2C9*2/*3, CYP2C9*3/*3]), Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend initiating celecoxib at a dosage that is 25–50% of the lowest recommended initial dosage (i.e., 50–75% dosage reduction) and cautiously titrating to a clinically effective dosage, up to a dosage that is 25–50% of the maximum recommended dosage.520 Do not increase dosage until steady-state concentrations are attained (≥8 days after initial dose).520 Alternatively, consider a drug that is not metabolized by CYP2C9 or is not substantially affected by CYP2C9 genetic variants in vivo.520 (See Pharmacogenomic Considerations under Cautions.)

For CYP2C9 intermediate metabolizers with AS of 1, CPIC guidelines recommend initiating celecoxib at the lowest recommended initial dosage and cautiously titrating to a clinically effective dosage, up to the maximum recommended dosage.520

Intermediate metabolizers with AS of 1.5 may receive dosages recommended for normal metabolizers.520

Detailed Celecoxib dosage information

Cautions for Celecoxib

Contraindications

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.1 103 104 113 116 122 123 129 130 131 134 137 138 139 140 141 146 147 148 500 502 508 Current evidence suggests cardiovascular risk with celecoxib may be dose related, with dosages >200 mg daily associated with greater risk.147 157 158 512

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.146 147 148 151 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Approximate threefold increase in risk of cardiovascular events (composite of cardiovascular death, MI, or stroke) observed with celecoxib 200 or 400 mg twice daily compared with placebo in the Adenoma Prevention with Celecoxib (APC) trial.1 508 Increase in risk mainly due to increased incidence of MI.1 508

Celecoxib 100 mg twice daily was not inferior to naproxen 375–500 mg twice daily or ibuprofen 600–800 mg 3 times daily with respect to risk of cardiovascular events (composite of cardiovascular death [including hemorrhagic death], MI, and stroke) in the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial.1 168 Data inadequate to assess risk at higher celecoxib dosage.1

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.1 102 112 500 508

Until more data are available, a selective COX-2 inhibitor remains an appropriate choice for patients at low cardiovascular risk who have had serious GI events, especially while receiving a prototypical NSAIA.112 121 128 145

Some clinicians state that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.1 508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 103 133 134 135 139 141 502 508 (See Specific Drugs under Interactions.)

GI Effects

Serious, sometimes fatal, GI toxicity (e.g., bleeding, ulceration, perforation of esophagus, stomach, or small or large intestine) can occur with or without warning symptoms.1 54

Risk for GI bleeding increased more than tenfold in patients with a history of peptic ulcer disease and/or GI bleeding who are receiving NSAIAs compared with patients without these risk factors.1 54 87

Other risk factors for GI bleeding include concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, or SSRIs; longer duration of NSAIA therapy (however, short-term therapy is not without risk); smoking; alcohol use; older age; poor general health status; and advanced liver disease and/or coagulopathy.1 54 87

Most spontaneous reports of fatal adverse GI effects involve geriatric or debilitated patients.1

Frequency of NSAIA-associated upper GI ulcers, gross bleeding, or perforation is approximately 1% in patients receiving NSAIAs for 3–6 months and 2–4% at one year.1

Lower risk of GI ulceration with celecoxib than with prototypical NSAIAs.1 2 3 9 21 22 24 28 29 33 38 65 66

Use at lowest effective dosage for the shortest duration necessary.1

Avoid use of more than one NSAIA at a time.1 (See Specific Drugs under Interactions.)

Avoid use of NSAIAs in patients at higher risk for GI toxicity unless expected benefits outweigh increased risk of bleeding; consider alternate therapies in high-risk patients and those with active GI bleeding.1

Monitor for GI ulceration and bleeding; even closer monitoring for GI bleeding recommended in those receiving concomitant low-dose aspirin for cardiac prophylaxis.1

If serious adverse GI event suspected, promptly initiate evaluation and discontinue celecoxib until serious adverse GI event ruled out.1

Other Warnings and Precautions

Hepatic Effects

Severe, sometimes fatal, reactions including fulminant hepatitis, liver necrosis, and hepatic failure reported rarely with NSAIAs.1

Elevations of serum ALT or AST reported with NSAIAs, including celecoxib.1

Monitor for symptoms and/or signs suggesting liver dysfunction.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur and evaluate the patient.1

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Monitor BP during initiation of celecoxib and throughout therapy.1

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.1 508 (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.1 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.1 500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

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.)

Correct fluid depletion prior to initiating celecoxib; monitor renal function during therapy in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.1

Hyperkalemia

Hyperkalemia reported with NSAIAs, even in some patients without renal impairment; in such patients, effects attributed to a hyporenin-hypoaldosterone state.1

Hypersensitivity Reactions

Anaphylactic reactions reported.1 Immediate medical intervention and discontinuance for anaphylaxis.1

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); in patients with asthma but without known aspirin sensitivity, monitor for changes in manifestations of asthma.1

Potentially fatal or life-threatening syndrome of multi-organ hypersensitivity (i.e., drug reaction with eosinophilia and systemic symptoms [DRESS]) reported in patients receiving NSAIAs.1201 Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy, and/or facial swelling, possibly associated with other organ system involvement (e.g., hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis).1201 Symptoms may resemble those of acute viral infection.1201 Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.1201 If signs or symptoms of DRESS develop, discontinue celecoxib and immediately evaluate the patient.1201

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis) 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

Medication Overuse Headache

Excessive use of drugs indicated for the management of acute migraine attacks (e.g., use of celecoxib, 5-HT1 receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for 10 or more days per month) may result in migraine-like daily headaches or a marked increase in the frequency of migraine attacks.161 Detoxification, including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often include transient worsening of headaches), may be necessary.161 (See Advice to Patients.)

Hematologic Effects

Anemia reported rarely.1 May be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.1 Determine hemoglobin concentration or hematocrit if signs or symptoms of anemia or blood loss occur.1

NSAIAs may increase the risk of bleeding.1 Patients with certain coexisting conditions (e.g., coagulation disorders) or receiving concomitant therapy with anticoagulants, antiplatelet agents, or serotonin-reuptake inhibitors may be at increased risk; monitor such patients for bleeding.1 (See Specific Drugs under Interactions.)

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 in these children; monitor coagulation tests and monitor for abnormal clotting or bleeding.1

Pharmacogenomic Considerations

CYP2C9 poor metabolizers: Celecoxib metabolism may be decreased substantially, half-life may be prolonged, and higher plasma concentrations of the drug may increase likelihood and/or severity of adverse effects.1 520 (See Elimination: Special Populations, under Pharmacokinetics.)

CYP2C9 intermediate metabolizers: Celecoxib metabolism may be moderately or mildly reduced in those with AS of 1 or 1.5, respectively.520 Higher plasma celecoxib concentrations in intermediate metabolizers with AS of 1 may increase likelihood of adverse effects.520 Presence of other factors affecting celecoxib clearance (e.g., hepatic impairment, advanced age) also may increase risk of adverse effects in intermediate metabolizers.520

Dosage reduction may be required based on CYP2C9 phenotype.520 (See CYP2C9 Poor or Intermediate Metabolizers under Dosage and Administration.)

Consult Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs for additional information on interpretation of CYP2C9 genotype testing.520

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

Use of Fixed Combinations

When the fixed combination of celecoxib and amlodipine is used, consider the cautions, precautions, contraindications, and drug interactions associated with both drugs.1201

Other Precautions

May mask certain signs of infection.1

Obtain CBC and chemistry profile periodically during long-term use.1

Specific Populations

Pregnancy

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.1200 1201

Effects of NSAIAs on the human fetus during third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.1202

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment, and consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.1200 1201 (See Advice to Patients.)

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.1200 1201 Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance.1200 1201 Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.1200 1201 In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.1200 1201 Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).1200 1201 Deaths associated with neonatal renal failure also reported.1200 Limitations of available data (lack of control group; limited information regarding dosage, duration, and timing of drug exposure; concomitant use of other drugs) preclude a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use.1201 Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.1201

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.1201 In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.1201

Adverse embryofetal effects (e.g., ventricular septal defects, sternebral fusion or abnormality, rib fusion, diaphragmatic hernias, pre- and post-implantation losses, reduced embryonic/fetal survival) observed in animal studies with celecoxib.1

Effects of celecoxib on labor and delivery not known.1 In animal studies, NSAIAs increased incidence of dystocia, delayed parturition, and decreased pup survival.1

Lactation

Distributes into milk in small amounts.1 161 1201 Calculated average daily infant exposure is <1% of the weight-based therapeutic dosage for a 2-year-old child.1 161 1201 Maternal use of celecoxib not associated with adverse effects in 2 breast-fed infants 17 and 22 months of age.1 161 1201

Not known whether celecoxib affects milk production.161 1201

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for celecoxib and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.1 161

Fertility

NSAIAs may be associated with reversible infertility in some women.1 Reversible delays in ovulation observed in limited studies in women receiving NSAIAs; animal studies indicate that inhibitors of prostaglandin synthesis can disrupt prostaglandin-mediated follicular rupture required for ovulation.1

Consider withdrawal of NSAIAs in women experiencing difficulty conceiving or undergoing evaluation of infertility.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

Consider alternatives to celecoxib in pediatric patients with juvenile rheumatoid arthritis who are known to be CYP2C9 poor metabolizers.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Safety and efficacy for acute treatment of migraine attacks not established in pediatric patients.161

Safety and efficacy of celecoxib in fixed combination with amlodipine not established in pediatric patients.1201

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 Monitor coagulation tests and monitor clinically for clotting abnormalities or bleeding.1

Not known whether long-term cardiovascular risks in children exposed to celecoxib are similar to those observed in adults receiving celecoxib or other NSAIAs.508 (See Cardiovascular Thrombotic Effects under Cautions.)

Geriatric Use

Increased risk for serious adverse cardiovascular, GI, and renal effects.1 161

Efficacy similar to that in younger adults.1 161 However, fatal adverse GI effects and acute renal failure reported more frequently in geriatric patients than younger adults.1

If anticipated benefits of celecoxib therapy outweigh potential risks, initiate celecoxib at lower end of the dosing range and monitor for adverse effects;1 if used for acute treatment of migraine attacks, use for the fewest possible number of days per month.161

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment.1 161

Reduced dosage recommended in patients with moderate hepatic impairment.1 161 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

May hasten the progression of renal dysfunction in patients with preexisting 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.1 161

Common Adverse Effects

Adults: Abdominal pain, diarrhea, dyspepsia, headache, nausea, sinusitis, upper respiratory tract infection.1 Dysgeusia in those receiving celecoxib oral solution for migraine attack.161

Children: Headache, fever, abdominal pain, cough, nasopharyngitis, nausea, arthralgia, diarrhea, vomiting.1

Drug Interactions

Metabolized by CYP2C9.77 Not a substrate for CYP2D6 in vitro.1

Inhibits CYP2D6; does not inhibit CYP2C9, CYP2C19, or CYP3A4.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP2C9 inhibitors: Possible increased celecoxib exposure and toxicity.1 3 44 Celecoxib dosage adjustment may be required.1 Examples include, but are not limited to, fluconazole, fluvastatin, and zafirlukast.1 3 44

CYP2C9 inducers: Possible reduced efficacy of celecoxib.1 Celecoxib dosage adjustment may be required.1 Examples include, but are not limited to, rifampin.1

CYP2D6 substrates: Possible increased exposure to and toxicity of CYP2D6 substrate drugs.1 3 6 44 Dosage adjustments may be required.1 Examples include, but are not limited to, various β-adrenergic blocking agents, many tricyclic and other antidepressants, various antipsychotic agents, atomoxetine, and some antiarrhythmics (e.g., encainide, flecainide).1 3 6 44

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor1

Possible reversible deterioration of renal function, including acute renal failure, in geriatric patients and patients with volume depletion or renal impairment1

Monitor BP1

Ensure adequate hydration; assess renal function when initiating concomitant therapy and periodically thereafter1

Monitor geriatric patients and patients with volume depletion or renal impairment for worsening renal function1

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonists1 153

Possible reversible deterioration of renal function, including acute renal failure, in geriatric patients and patients with volume depletion or renal impairment1

Monitor BP1 153

Ensure adequate hydration; assess renal function when initiating concomitant therapy and periodically thereafter1

Monitor geriatric patients and patients with volume depletion or renal impairment for worsening renal function1

Antacids (magnesium- or aluminum-containing)

Decreased plasma concentration and AUC of celecoxib1 50

Not considered clinically important1 50

Anticoagulants

Synergistic effects on GI bleeding; higher risk of serious bleeding compared with either agent alone1

Warfarin: Reports of bleeding complications and increases in PT in some (mainly geriatric) patients1 56 57

Increased risk of major bleeding or supratherapeutic INRs in patients with reduced CYP2C9 function receiving concomitant warfarin (CYP2C9 substrate) and NSAIAs520

Monitor anticoagulant activity, especially when initiating or changing celecoxib therapy1 56 57

Monitor for bleeding1

Some experts recommend avoiding concomitant use of warfarin and NSAIAs in CYP2C9 intermediate or poor metabolizers520

β-Adrenergic blocking agents

Reduced BP response to β-blocker1

Monitor BP1

Corticosteroids

Possible increased risk of GI ulceration or bleeding1

Monitor for bleeding1

Cyclosporine

Possible increased cyclosporine-associated nephrotoxicity1

Monitor for worsening renal function1

Digoxin

Increased serum concentrations and prolonged half-life of digoxin1

Monitor serum digoxin concentrations1

Diuretics (furosemide, thiazides)

Reduced natriuretic effects1

Monitor for worsening renal function and for adequacy of diuretic and antihypertensive effects1

Fluconazole

Increased plasma celecoxib concentrations (due to CYP2C9 inhibition)1

Celecoxib dosage adjustment may be required1

Glyburide

No clinically important pharmacokinetic or pharmacodynamic interaction1

Ketoconazole

No clinically important pharmacokinetic or pharmacodynamic interaction1

Lithium

Decreased renal clearance of lithium, resulting in increased serum or plasma lithium concentrations1 36

Monitor for lithium toxicity1

Methotrexate

Possible increased risk of methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction) with concomitant NSAIA and methotrexate use; however, pharmacokinetics of methotrexate not altered by celecoxib in clinical studies1

Monitor for methotrexate toxicity1

NSAIAs

Concomitant NSAIAs and aspirin (analgesic dosages): Therapeutic effect not greater than that of NSAIAs alone1

Concomitant NSAIAs and aspirin: Increased risk for bleeding and serious GI ulceration1 33 79

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs1 103 133 134 139 141 502 508

Concomitant use of celecoxib with other NSAIAs or analgesic dosages of aspirin generally not recommended1

Advise patients not to take low-dose aspirin without consulting clinician;1 closely monitor patients receiving concomitant antiplatelet agents (e.g., aspirin) for bleeding1

Pemetrexed

Possible increased risk of pemetrexed-associated myelosuppression, renal toxicity, and GI toxicity1

Short half-life NSAIAs (e. g., diclofenac, indomethacin): Avoid administration beginning 2 days before and continuing through 2 days after pemetrexed administration1

Longer half-life NSAIAs (e.g., meloxicam, nabumetone): In the absence of data, avoid administration beginning at least 5 days before and continuing through 2 days after pemetrexed administration1

Patients with Clcr 45–79 mL/minute: Monitor for myelosuppression, renal toxicity, and GI toxicity1

Phenytoin

No clinically important pharmacokinetic or pharmacodynamic interaction1

Serotonin-reuptake inhibitors (e.g., SSRIs, SNRIs)

Possible increased risk of bleeding due to importance of serotonin release by platelets in hemostasis1

Monitor for bleeding1

Tolbutamide

No clinically important pharmacokinetic or pharmacodynamic interaction1
Celecoxib drug interactions (more detail)

Celecoxib Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentration usually attained within 3 hours in fasting individuals.1 2 23

Celecoxib/amlodipine fixed-combination tablets: Peak celecoxib concentrations attained within 2 hours.1201

Celecoxib oral solution: Faster rate of absorption and increased bioavailability compared with oral capsules.166 In fasting individuals, median time to peak plasma concentrations was 1 hour.161 166

Onset

Single doses provide pain relief within 60 minutes.1

Food

Celecoxib capsules: 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 of capsule contents as mixture in applesauce does not alter AUC, peak plasma concentration, or time to peak plasma concentration.1

Celecoxib oral solution: Peak plasma concentration delayed by 2 hours and decreased by approximately 50% when administered with a high-fat meal; no change in AUC.161 However, oral solution was administered without regard to food in the principal clinical trials establishing efficacy for acute treatment of migraine.161

Celecoxib/amlodipine fixed-combination tablets: Rate and extent of celecoxib absorption similar under fed and fasting conditions.1201

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

Mean apparent elimination half-life approximately 6 hours, independent of dosing conditions, when administered as oral solution; half-life similar to that observed for celecoxib capsules under fed conditions.161

Special Populations

CYP2C9 poor metabolizers with CYP2C9*3/*3 diplotype: Limited data indicate celecoxib concentrations are increased threefold to sevenfold compared with individuals with CYP2C9*1/*1 or CYP2C9*1/*3 diplotypes.1 Data lacking on other CYP2C9 polymorphisms.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

Solution

20–25°C (may be exposed to 15–30°C); do not refrigerate or freeze.161 Discard any unused portion remaining in the disposable unit-dose glass bottle immediately after use.161

Tablets Containing Celecoxib and Amlodipine

20–25°C.1201

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Celecoxib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

50 mg*

CeleBREX

Pfizer

Celecoxib Capsules

100 mg*

CeleBREX

Pfizer

Celecoxib Capsules

200 mg*

CeleBREX

Pfizer

Celecoxib Capsules

400mg*

CeleBREX

Pfizer

Celecoxib Capsules

Solution

120 mg/4.8 mL

Elyxyb

Dr. Reddy's
Celecoxib Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

200 mg with Amlodipine Besylate 2.5 mg (of amlodipine)

Consensi

Burke

200 mg with Amlodipine Besylate 5 mg (of amlodipine)

Consensi

Burke

200 mg with Amlodipine Besylate 10 mg (of amlodipine)

Consensi

Burke

56 mg with tramadol hydrochloride 44 mg

Seglentis (C-V)

Kowa

AHFS DI Essentials™. © Copyright 2024, Selected Revisions August 25, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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99. Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomized controlled trials. BMJ; 325:619-23.

100. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10. http://www.ncbi.nlm.nih.gov/pubmed/12501222?dopt=AbstractPlus

101. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. http://www.ncbi.nlm.nih.gov/pubmed/12501230?dopt=AbstractPlus

102. Clark DWJ, Layton D, Shakir SAW. Do some inhibitors of COX-2 increase the risk of thromboembolic events? Drug Safety. 2004; 27:427-56.

103. Bresalier RS, Sandler RS, Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005; 352:1092-102. http://www.ncbi.nlm.nih.gov/pubmed/15713943?dopt=AbstractPlus

104. Merck. Merck announces voluntary worldwide withdrawal of Vioxx. Whitehouse Station, NJ; 2004 Sep 30. Press release.

105. Couzin J. Drug safety: withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science. 2004; 306:384-5. http://www.ncbi.nlm.nih.gov/pubmed/15486258?dopt=AbstractPlus

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