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Celecoxib

Class: Cyclooxygenase-2 (COX-2) Inhibitors
- COX-2 Inhibitors
Chemical Name: 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
CAS Number: 184007-95-2
Brands: CeleBREX, Elyxyb

Medically reviewed by Drugs.com on Oct 18, 2021. Written by ASHP.

Warning

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

  • Contraindicated in the setting of CABG surgery.

    GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine). Serious GI events can occur at any time and may not be preceded by warning signs and symptoms. Geriatric individuals and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. (See GI Effects under Cautions.)

Introduction

NSAIA that is a selective inhibitor of cyclooxygenase-2 (COX-2); diaryl-substituted pyrazole derivative containing a sulfonamide substituent.

Uses for Celecoxib

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

Osteoarthritis

Symptomatic treatment of osteoarthritis. Effect comparable to that of prototypical NSAIAs (naproxen).

Lower incidence of endoscopically confirmed GI ulcer and serious adverse GI effects than prototypical NSAIAs.

Rheumatoid Arthritis in Adults

Symptomatic treatment of rheumatoid arthritis in adults. Effect comparable to that of prototypical NSAIAs (naproxen, diclofenac).

Lower incidence of endoscopically confirmed GI ulcer and serious adverse GI effects than prototypical NSAIAs.

Juvenile Arthritis

Symptomatic management of pauciarticular course, polyarticular course, or systemic onset juvenile rheumatoid arthritis in children ≥2 years of age. Effect comparable to that of naproxen.

Ankylosing Spondylitis

Management of the signs and symptoms of ankylosing spondylitis.

Colorectal Polyps

Has been used to reduce the number of adenomatous colorectal polyps (colorectal adenomas) in adults with familial adenomatous polyposis (FAP) as an adjunct to usual care. 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. Labeled indication was withdrawn because patient accrual in the study was slow and manufacturer was unable to provide confirmatory data. 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.

Has been investigated for the prevention of colorectal adenomas in patients without a history of FAP. Use of celecoxib reduces the risk of recurrent colorectal adenomas; not known whether celecoxib reduces the risk of colorectal cancer. Routine use not recommended because of the potential for serious cardiovascular events.

Pain

Management of acute pain, including postoperative (e.g., dental, orthopedic) pain, in adults.

Migraine

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

Dysmenorrhea

Symptomatic management of primary dysmenorrhea in adults.

Cardiovascular Risk Reduction

Not a substitute for aspirin in the prevention of adverse cardiovascular events (MI). (See Cardiovascular Thrombotic Effects under Cautions.)

Celecoxib Dosage and Administration

General

  • Consider potential benefits and risks of celecoxib therapy as well as alternative therapies before initiating therapy with the drug.

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.

Capsules

Administer dosages up to 200 mg twice daily without regard to meals; administer higher dosages (400 mg twice daily) with food.

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.

Celecoxib/Amlodipine Fixed-combination Tablets

For once-daily administration only.

Oral Solution

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

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. Consult manufacturer's instructions for use for additional information on administration.

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.

Attempt to titrate to the lowest effective dosage in adults with arthritis.

Pediatric Patients

Juvenile Arthritis
Oral

Children ≥2 years of age weighing 10–25 kg: 50 mg twice daily.

Children ≥2 years of age weighing >25 kg: 100 mg twice daily.

Adults

Osteoarthritis
Oral

200 mg daily as a single dose or in 2 equally divided doses.

No additional benefit from dosages >200 mg daily.

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

Rheumatoid Arthritis in Adults
Oral

100–200 mg twice daily.

No additional benefit from higher dosages (400 mg twice daily).

Ankylosing Spondylitis
Oral

Initially, 200 mg daily as a single dose or in 2 equally divided doses. If no response observed after 6 weeks, increase to 400 mg daily. If no response observed after 400 mg daily for 6 weeks, response is unlikely; consider alternative therapies.

Colorectal Polyps
Oral

400 mg twice daily.

Pain
Oral

400 mg initially as a single dose, followed by an additional dose of 200 mg, if necessary, on the first day. For continued relief, 200 mg twice daily as needed.

Migraine
Acute Treatment
Oral

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

Dysmenorrhea
Oral

400 mg initially as a single dose, followed by an additional dose of 200 mg, if necessary, on the first day. For continued relief, 200 mg twice daily as needed.

Prescribing Limits

Adults

Migraine
Acute Treatment
Oral

Maximum 120 mg per 24-hour period.

Special Populations

Hepatic Impairment

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

Severe hepatic impairment: Use not recommended.

Renal Impairment

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

Severe renal impairment: Use not recommended. (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.

CYP2C9 Poor or Intermediate Metabolizers

Known or suspected CYP2C9 poor metabolizers with CYP2C9*3/*3 diplotype: Manufacturer recommends reducing initial dosage by 50%. Recommended and maximum dosage for acute treatment of migraine attacks is 60 mg. (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.

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. Do not increase dosage until steady-state concentrations are attained (≥8 days after initial dose). Alternatively, consider a drug that is not metabolized by CYP2C9 or is not substantially affected by CYP2C9 genetic variants in vivo. (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.

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

Cautions for Celecoxib

Contraindications

  • Known hypersensitivity (e.g., anaphylaxis, serious dermatologic reactions) to celecoxib, sulfonamides, or any ingredient in the formulation.

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.

  • In the setting of CABG surgery.

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. Current evidence suggests cardiovascular risk with celecoxib may be dose related, with dosages >200 mg daily associated with greater risk.

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

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.

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

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.

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

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; 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.

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. FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.

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. Increase in risk mainly due to increased incidence of MI.

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. Data inadequate to assess risk at higher celecoxib dosage.

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.

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.

Some clinicians state that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease. 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. Contraindicated in the setting of CABG surgery.

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs. (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.

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.

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.

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

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.

Lower risk of GI ulceration with celecoxib than with prototypical NSAIAs.

Use at lowest effective dosage for the shortest duration necessary.

Avoid use of more than one NSAIA at a time. (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.

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

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

Other Warnings and Precautions

Hepatic Effects

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

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

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

Hypertension

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

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

Heart Failure and Edema

Fluid retention and edema reported.

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema. (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.

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

Renal Effects

Adverse renal effects similar to those of prototypical NSAIAs.

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.

Potential for overt renal decompensation. 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. (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.

Hyperkalemia

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

Hypersensitivity Reactions

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

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.

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. 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). Symptoms may resemble those of acute viral infection. Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash. If signs or symptoms of DRESS develop, discontinue celecoxib and immediately evaluate the patient.

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. Discontinue at first appearance of rash or any other sign of hypersensitivity (blisters, fever, pruritus).

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. Detoxification, including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often include transient worsening of headaches), may be necessary. (See Advice to Patients.)

Hematologic Effects

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

NSAIAs may increase the risk of bleeding. 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. (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. Use with caution in these children; monitor coagulation tests and monitor for abnormal clotting or bleeding.

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. (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. Higher plasma celecoxib concentrations in intermediate metabolizers with AS of 1 may increase likelihood of adverse effects. Presence of other factors affecting celecoxib clearance (e.g., hepatic impairment, advanced age) also may increase risk of adverse effects in intermediate metabolizers.

Dosage reduction may be required based on CYP2C9 phenotype. (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.

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.

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.

Other Precautions

May mask certain signs of infection.

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

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.

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.

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. (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. Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios. Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis). Deaths associated with neonatal renal failure also reported. 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. Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.

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

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.

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

Lactation

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

Not known whether celecoxib affects milk production.

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.

Fertility

NSAIAs may be associated with reversible infertility in some women. 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.

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

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. Safety and efficacy not established in children <2 years of age, those weighing <10 kg, or children with active systemic disease. Not studied beyond 6 months.

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

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

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

Children with systemic onset juvenile rheumatoid arthritis: Risk of abnormal coagulation test results; modest prolongation of aPTT reported. Risk of disseminated intravascular coagulation. Monitor coagulation tests and monitor clinically for clotting abnormalities or bleeding.

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

Geriatric Use

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

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

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

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment.

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

Renal Impairment

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

No experience in patients with advanced renal disease; use not recommended in such patients; close monitoring of renal function advised if used.

Common Adverse Effects

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

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

Interactions for Celecoxib

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

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

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

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

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

CYP2D6 substrates: Possible increased exposure to and toxicity of CYP2D6 substrate drugs. Dosage adjustments may be required. 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).

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor

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

Monitor BP

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

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

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonists

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

Monitor BP

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

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

Antacids (magnesium- or aluminum-containing)

Decreased plasma concentration and AUC of celecoxib

Not considered clinically important

Anticoagulants

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

Warfarin: Reports of bleeding complications and increases in PT in some (mainly geriatric) patients

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

Monitor anticoagulant activity, especially when initiating or changing celecoxib therapy

Monitor for bleeding

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

β-Adrenergic blocking agents

Reduced BP response to β-blocker

Monitor BP

Corticosteroids

Possible increased risk of GI ulceration or bleeding

Monitor for bleeding

Cyclosporine

Possible increased cyclosporine-associated nephrotoxicity

Monitor for worsening renal function

Digoxin

Increased serum concentrations and prolonged half-life of digoxin

Monitor serum digoxin concentrations

Diuretics (furosemide, thiazides)

Reduced natriuretic effects

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

Fluconazole

Increased plasma celecoxib concentrations (due to CYP2C9 inhibition)

Celecoxib dosage adjustment may be required

Glyburide

No clinically important pharmacokinetic or pharmacodynamic interaction

Ketoconazole

No clinically important pharmacokinetic or pharmacodynamic interaction

Lithium

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

Monitor for lithium toxicity

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 studies

Monitor for methotrexate toxicity

NSAIAs

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

Concomitant NSAIAs and aspirin: Increased risk for bleeding and serious GI ulceration

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs

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

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

Pemetrexed

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

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

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 administration

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

Phenytoin

No clinically important pharmacokinetic or pharmacodynamic interaction

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

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

Monitor for bleeding

Tolbutamide

No clinically important pharmacokinetic or pharmacodynamic interaction

Celecoxib Pharmacokinetics

Absorption

Bioavailability

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

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

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

Onset

Single doses provide pain relief within 60 minutes.

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. Administration of dosages of 400 mg twice daily with food improves absorption.

Administration of capsule contents as mixture in applesauce does not alter AUC, peak plasma concentration, or time to peak plasma concentration.

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. However, oral solution was administered without regard to food in the principal clinical trials establishing efficacy for acute treatment of migraine.

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

Special Populations

In geriatric patients, peak plasma concentration and AUC increased by 40 and 50%, respectively.

In patients with mild or moderate hepatic impairment, AUC increased by 40 or 180%, respectively.

In patients with chronic renal impairment (GFR 35–60 mL/minute), AUC decreased by 40%; pharmacokinetics not studied in patients with severe renal impairment.

Distribution

Extent

Not well characterized.

Plasma Protein Binding

97% (principally albumin; α1-acid glycoprotein to a lesser extent).

Elimination

Metabolism

Metabolized in the liver to inactive metabolites, mainly by CYP2C9.

Elimination Route

Excreted in urine and feces principally as metabolites.

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.

Half-life

11 hours under fasting conditions.

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.

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. Data lacking on other CYP2C9 polymorphisms.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Mixture of capsule contents in applesauce is stable for 6 hours when refrigerated.

Solution

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

Tablets Containing Celecoxib and Amlodipine

20–25°C.

Actions

  • Selective inhibitor of COX-2.

  • 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.

  • Anti-inflammatory, analgesic, and antipyretic actions; no effect on platelets at usual therapeutic doses; may reduce risk of colon cancer.

  • Lower risk of GI ulceration than prototypical NSAIAs.

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.

  • Risk of serious cardiovascular events (e.g., MI, stroke). Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (e.g., chest pain, dyspnea, weakness, slurred speech) occur.

  • Risk of GI bleeding and ulceration. Inform patients receiving concomitant low-dose aspirin of increased risk of GI bleeding. Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding develop.

  • Risk of serious skin reactions, DRESS, and anaphylactic and other sensitivity reactions. Advise patients to stop taking celecoxib immediately if they develop any type of rash or fever and to promptly contact their clinician. Importance of seeking immediate medical attention if an anaphylactic reaction occurs.

  • Risk of hepatotoxicity. Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.

  • Not a substitute for aspirin in the prevention of adverse cardiovascular events.

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of avoiding NSAIA use beginning at 20 weeks’ gestation unless otherwise advised by a clinician; importance of avoiding NSAIAs beginning at 30 weeks’ gestation because of risk of premature closure of the fetal ductus arteriosus; monitoring for oligohydramnios may be necessary if NSAIA therapy required for >48 hours’ duration between about 20 and 30 weeks’ gestation.

  • Advise women who are trying to conceive that NSAIAs may be associated with a reversible delay in ovulation.

  • Advise patients with migraine headaches that overuse of drugs intended for acute treatment of migraine attacks (e.g., use on ≥10 days per month) may exacerbate headaches; encourage patients to record the frequency of migraine headaches and medication use and to contact their clinician if the frequency of migraine attacks increases.

  • Importance of advising patients on appropriate administration of celecoxib oral solution for acute treatment of migraine attacks.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. Advise patients that concomitant use of other NSAIAs with celecoxib provides little or no increase in efficacy but increases risk of GI toxicity, and is not recommended. Advise patients not to use concomitant low-dose aspirin without consulting their clinician. Alert patients to the presence of NSAIAs in many OTC drugs.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

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

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 18, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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