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

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Nonsteroidal anti-inflammatory agent (NSAIA);^{1 3 4 5 8 11 41} selective inhibitor of cyclooxygenase-2 (COX-2).^{1 8}

Uses for Celecoxib

Osteoarthritis

Symptomatic treatment of osteoarthritis.^{1 3 9 28 29 64 1999}

The American College of Rheumatology (ACR) recommends topical/oral NSAIAs for treatment of osteoarthritis, among other interventions.³² Therapy selection is patient-specific; factors to consider include patient values and preferences, risk factors for serious adverse GI effects, existing comorbidities (e.g., hypertension, heart failure, other cardiovascular disease, chronic kidney disease), injuries, disease severity, surgical history, and access to and availability of interventions.³²

Rheumatoid Arthritis in Adults

Symptomatic treatment of rheumatoid arthritis in adults.^{1 3 9 10 21 22 23 24 28 65 66 2000}

ACR guidelines recommend initiation of a disease-modifying antirheumatic drug (DMARD) for most patients with rheumatoid arthritis; role of NSAIAs not discussed.²⁰⁰¹

Juvenile Rheumatoid Arthritis

Symptomatic management of juvenile rheumatoid arthritis in children ≥2 years of age.^{1 2002}

ACR and the Arthritis Foundation recommend initial therapy with a DMARD (e.g., methotrexate) over NSAIA monotherapy for children and adolescents with juvenile idiopathic arthritis and polyarthritis; NSAIAs may be used adjunctively, particularly during initiation or escalation of therapy with DMARDs or biologics.²⁰⁰³ For patients with active sacroiliitis or enthesitis, initial treatment with an NSAIA is recommended; no particular NSAIA is preferred.²⁰⁰³

Ankylosing Spondylitis

Management of the signs and symptoms of ankylosing spondylitis in adults.^{1 132 2007}

ACR guidelines recommend NSAIAs as one of several treatment options for ankylosing spondylitis.²⁰⁰⁸ Specific agents are selected according to current disease activity, prior therapies, and presence of comorbidities.²⁰⁰⁸

Acute Pain

Management of acute pain in adults.^{1 8 2009}

Current guidelines on postoperative pain management recommend a multimodal approach to analgesia.²⁰¹³ NSAIAs and/or acetaminophen are recommended as part of multimodal analgesia in patients without contraindications.²⁰¹³ When selecting therapy, consider potential risks associated with NSAIAs; celecoxib may carry a lower risk of GI bleeding/ulceration compared with other NSAIAs.²⁰¹³ If no contraindications exist, the guidelines state to consider a preoperative dose of celecoxib (200–400 mg given 30–60 minutes prior to surgery) in adults undergoing major surgery.²⁰¹³

Primary Dysmenorrhea

Symptomatic management of primary dysmenorrhea in adults.^{1 2014}

First-line treatment options for primary dysmenorrhea include combined oral contraceptives, progesterone-only contraceptives, and NSAIAs; treatment selection should be based on patient-specific considerations (e.g., comorbidities, desire/need for contraception).^{2012 2015} The American College of Obstetricians and Gynecologists includes celecoxib as a potential NSAIA for use in patients ≥18 years of age with primary dysmenorrhea, but does not recommend one NSAIA over another.²⁰¹²

Migraine

Acute treatment of migraine with or without aura; oral solution specifically FDA-labeled for this use.^{161 2021 2022 2023}

Should not be used for prevention of migraine.¹⁶¹

The American Headache Society (AHS) guidelines include NSAIAs (aspirin, celecoxib oral solution, diclofenac, ibuprofen, naproxen) as one of several drug classes with established efficacy in the acute treatment of migraine.²⁰²⁴ Nonspecific analgesic therapies such as NSAIAs are used for mild-to-moderate attacks, while migraine-specific therapies (e.g., triptans, ergotamine derivatives, small-molecule calcitonin gene-related peptide [CGRP] receptor antagonists [gepants], lasmiditan) are used for moderate-to-severe attacks or mild-to-moderate attacks that respond poorly to nonspecific therapy.²⁰²⁴ Selection of an agent should be based on patient-specific factors such as comorbid disease states, individual treatment history, and concomitant medications.²⁰²⁴

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 2017} 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; not known whether celecoxib reduces the risk of colorectal cancer.^{149 150} Routine use not recommended because of potential for serious cardiovascular events.¹⁴⁹

Celecoxib Dosage and Administration

General

Patient Monitoring

• Monitor blood pressure during initiation of celecoxib and throughout therapy.^{1 161}

• Monitor patients (including those without previous symptoms of cardiovascular disease) for the possible development of cardiovascular events throughout therapy.^{1 161}

• Monitor for signs and symptoms of GI bleeding or ulceration.^{1 161}

• Monitor for signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritis, jaundice, right upper quadrant tenderness, flu-like symptoms).^{1 161}

• Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.^{1 161}

• Monitor for changes in asthma signs and symptoms when using celecoxib in patients with preexisting asthma.^{1 161}

• Perform periodic CBC and chemistry profiles in patients receiving long-term celecoxib therapy.^{1 161}

• Monitor hemoglobin or hematocrit if signs and/or symptoms of anemia occur during therapy with celecoxib.^{1 161}

• Monitor pediatric patients with systemic onset juvenile rheumatoid arthritis receiving celecoxib for clinical signs and symptoms of abnormal clotting or bleeding.^{1 161}

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Celebrex (celecoxib), Celexa (citalopram hydrobromide), and Cerebyx (fosphenytoin sodium) on their ISMP List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs.³⁴

Other General Considerations

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.¹

• When used for migraine, use for the fewest number of days per month, as needed.¹⁶¹

Administration

Oral Administration

Administer orally.^{1 161}

Available as capsules and oral solution; oral solution is FDA-labeled for treatment of migraine only.^{1 161}

Capsules

Administer without regard to meals.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

Oral Solution

Administer 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.¹⁶¹

Dosage

Pediatric Patients

Juvenile Rheumatoid Arthritis

Oral

Children ≥2 years of age weighing >10 kg to <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

No additional benefit from dosages >200 mg daily.¹

Rheumatoid Arthritis

Oral

100–200 mg twice daily.¹

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

Acute 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

Primary 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, may administer 200 mg twice daily as needed.¹

Migraine

Acute Treatment

Oral

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

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment of oral solution necessary for acute treatment of migraine attacks.¹⁶¹

Moderate hepatic impairment (Child-Pugh Class B): Reduce dosage of oral capsules by 50%;¹ recommended and maximum dosage of oral solution for acute treatment of migraine attacks is 60 mg.¹⁶¹

Severe hepatic impairment (Child-Pugh Class C): Use not recommended.^{1 161}

Renal Impairment

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

Severe renal impairment: Use not recommended.^{1 161}

Geriatric Patients

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

Pharmacogenomic Considerations in Dosing

Known or suspected CYP2C9 poor metabolizers with CYP2C9*3/*3 diplotype: Manufacturer of celecoxib capsules recommends reducing initial dosage by 50%.¹ Recommended and maximum dosage of oral solution for acute treatment of migraine attacks is 60 mg.¹⁶¹

Manufacturer of capsules states to 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

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

Cautions for Celecoxib

Contraindications

• Known hypersensitivity (e.g., anaphylaxis, serious dermatologic reactions) to the drug, sulfonamides, or any ingredient in the formulation.^{1 161}

• History of asthma, urticaria, or other sensitivity reactions after taking aspirin or other NSAIAs.^{1 161}

• Contraindicated in the setting of CABG surgery.^{1 161}

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

Increased risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) (see Boxed Warning).^{1 161} All NSAIAs potentially associated with increased cardiovascular risk; unknown if risk differs across NSAIAs.^{1 161}

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of elevated baseline risk.^{1 161}

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.^{1 161}

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.^{1 161}

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.^{1 161}

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; 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.^{1 161}

Use NSAIAs at lowest effective dosage for shortest duration necessary.^{1 161} In patients receiving celecoxib for migraine, use as needed for the fewest possible number of days per month.¹⁶¹

Monitor patients for cardiovascular events throughout therapy.^{1 161} Avoid celecoxib use in patients with recent MI unless benefits are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.^{1 161}

Contraindicated in the setting of CABG surgery.^{1 161 161}

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.^{1 161} Concomitant use of aspirin and celecoxib increases risk of serious GI events.^{1 161}

GI Bleeding, Ulceration, and Perforation

Serious, sometimes fatal, GI toxicity (e.g., bleeding, ulceration, perforation of stomach, or small or large intestine) can occur with or without warning symptoms (see Boxed Warning).^{1 161}

Risk of GI bleeding increased more than 10-fold in patients with a history of peptic ulcer disease and/or GI bleeding.^{1 161}

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.^{1 161}

Most spontaneous reports of fatal adverse GI effects involve geriatric or debilitated patients.^{1 161}

Use lowest effective dosage for shortest duration necessary.^{1 161}

Avoid use of more than one NSAIA at a time.^{1 161}

Avoid use 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.^{1 161}

Monitor for GI ulceration and bleeding; closer monitoring for GI bleeding recommended in those receiving concomitant low-dose aspirin for cardiac prophylaxis.^{1 161}

If serious adverse GI event suspected, promptly evaluate and discontinue celecoxib until serious adverse GI event ruled out.^{1 161}

Other Warnings and Precautions

Hepatotoxicity

Severe, sometimes fatal, reactions, including fulminant hepatitis, liver necrosis, and hepatic failure, reported rarely with NSAIAs.^{1 161}

Elevations of serum ALT or AST reported with NSAIAs, including celecoxib.^{1 161}

Monitor for symptoms and/or signs suggesting liver dysfunction.^{1 161} Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur^{1 161}

Monitor for signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritis, jaundice, right upper quadrant tenderness, flu-like symptoms).^{1 161}

Hypertension

Onset or worsening of hypertension reported; may contribute to increased incidence of cardiovascular events.^{1 161} Monitor BP during initiation of celecoxib and throughout therapy.^{1 161}

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.^{1 161}

Heart Failure and Edema

Fluid retention and edema reported.^{1 161}

NSAIAs (selective COX-2 inhibitors or nonselective NSAIAs) are associated with increased risk of death, MI, and hospitalization for heart failure in patients with heart failure.^{1 161}

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.^{1 161}

Avoid use in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.^{1 161}

Renal Toxicity and Hyperkalemia

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.^{1 161}

Potential for overt renal decompensation.^{1 161} 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.^{1 161}

Correct fluid depletion prior to initiating celecoxib; monitor renal function during therapy in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.^{1 161}

Use of celecoxib not recommended in patients with advanced renal disease unless the benefits of therapy are expected to outweigh the potential risk of worsening renal function.^{1 161} If used in patients with advanced renal disease, monitor for signs of worsening renal function.¹

Hyperkalemia reported with NSAIAs, even in some patients without renal impairment; in such patients, effects attributed to a hyporenin-hypoaldosterone state.^{1 161}

Anaphylactic Reactions

Anaphylactic reactions reported.^{1 161} Celecoxib is a sulfonamide; both NSAIAs and sulfonamides may cause allergic-type reactions, including anaphylactic symptoms.^{1 161}

Contraindicated in patients with known hypersensitivity to celecoxib or any components of the formulation, as well as patients with known sulfonamide allergy or history of asthma, urticaria, or other allergic-type reactions to aspirin or other NSAIAs.^{1 161}

Seek emergency medical assistance if any anaphylactic reaction occurs.¹

Exacerbations of Asthma Related to Aspirin Sensitivity

Contraindicated in patients with aspirin-sensitive asthma because cross-reactivity between aspirin and other NSAIAs has been reported in aspirin-sensitive patients; in patients with asthma but without known aspirin sensitivity, monitor for changes in manifestations of asthma.^{1 161}

Serious Skin Reactions

Serious skin reactions (e.g., erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis) reported; can occur without warning and may be fatal.^{1 161}

Contraindicated in patients with previous serious skin reactions to NSAIAs.^{1 161} Discontinue at first appearance of rash or any other sign of hypersensitivity.^{1 161}

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Potentially fatal or life-threatening drug reaction with eosinophilia and systemic symptoms (DRESS) reported in patients receiving NSAIAs.^{1 161} 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).^{1 161}

Symptoms may resemble those of acute viral infection.^{1 161} Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.^{1 161}

If signs or symptoms of DRESS develop, discontinue celecoxib and immediately evaluate patient.^{1 161}

Hematologic Toxicity

Anemia reported.^{1 161} May be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.^{1 161}

Check hemoglobin and hematocrit if signs or symptoms of anemia or blood loss occur.^{1 161}

NSAIAs may increase risk of bleeding.^{1 161} Patients with certain coexisting conditions (e.g., coagulation disorders) or receiving concomitant therapy with anticoagulants, antiplatelet agents, SSRIs, or SNRIs may be at increased risk; monitor such patients for bleeding.^{1 161}

Disseminated Intravascular Coagulation (DIC)

Risk of DIC in children with systemic onset juvenile rheumatoid arthritis.^{1 161} Monitor for abnormal clotting or bleeding, and inform the patients and their caregivers to report symptoms as soon as possible.^{1 161}

Laboratory Monitoring

Obtain CBC and chemistry profile periodically during long-term use.^{1 161}

Masking of Inflammation and Fever

Anti-inflammatory and anti-pyretic effects may mask certain signs of infection.^{1 161}

Medication Overuse Headache

Excessive use of drugs indicated for the management of acute migraine attacks (e.g., use of NSAIAs, 5-HT₁ receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 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

Fetal/Neonatal Morbidity and Mortality

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.^{1 161}

Fetal renal dysfunction observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.^{1 161} Oligohydramnios often, but not always, reversible following NSAIA discontinuance.^{1 161} Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.^{1 161} In rare cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.^{1 161} Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).^{1 161}

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.^{1 161} In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.^{1 161}

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.^{1 161}

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.^{1 161}

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.^{1 161}

Fetal renal dysfunction observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.^{1 161} Oligohydramnios often, but not always, reversible following NSAIA discontinuance.^{1 161} Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.^{1 161} In rare cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.^{1 161} Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).^{1 161}

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.^{1 161} In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.^{1 161}

Effects of celecoxib on labor and delivery not known.^{1 161} In animal studies, NSAIAs delayed parturition and increased stillbirth.^{1 161}

Lactation

Distributes into milk in small amounts.^{1 161} Calculated average daily infant exposure is <1% of the weight-based therapeutic dosage for a 2-year-old child.^{1 161} 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.¹⁶¹

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}

Females and Males of Reproductive Potential

NSAIAs may be associated with reversible infertility in some women.^{1 161} Reversible delays in ovulation observed in limited studies in women receiving NSAIAs.^{1 161}

Consider withdrawal of celecoxib in women experiencing difficulty conceiving or undergoing evaluation of infertility.^{1 161}

Pediatric Use

Safety and efficacy in pediatric patients 2–17 years of age with pauciarticular course, polyarticular course, or systemic onset juvenile rheumatoid arthritis supported by evidence from a clinical study.¹ Safety and efficacy not established in pediatric patients <2 years of age, those weighing <10 kg, or those 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

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

Pediatric patients with systemic onset juvenile rheumatoid arthritis are at risk of DIC.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.¹

Geriatric Use

NSAIAs increased risk for serious adverse cardiovascular, GI, and renal effects.^{1 161}

Efficacy of celecoxib 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 In geriatric patients weighing <50 kg, initiate celecoxib therapy at the lowest recommended dosage.¹

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment (Child-Pugh Class C).^{1 161}

Reduced dosage recommended in patients with moderate hepatic impairment (Child-Pugh Class B).^{1 161}

Renal Impairment

May hasten the progression of renal dysfunction in patients with preexisting renal disease.^{1 161}

No experience in patients with advanced renal disease; use not recommended in such patients unless benefits are expected to outweigh risk; close monitoring of renal function advised if used.^{1 161}

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}

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

Consult CPIC guideline for additional information on interpretation of CYP2C9 genotype testing.⁵²⁰

Common Adverse Effects

Adverse effects (>2%) in adult patients receiving celecoxib for arthritis: abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, rash.¹ Adverse events in adult patients receiving celecoxib for ankylosing spondylitis, analgesia, and dysmenorrhea in clinical trials were similar to those reported in the osteoarthritis and rheumatoid arthritis trials.¹

Adverse events (≥5%) in pediatric patients receiving celecoxib for juvenile rheumatoid arthritis: headache, pyrexia, upper abdominal pain, cough, nasopharyngitis, abdominal pain, nausea, arthralgia, diarrhea, vomiting.¹

Most common adverse effect (≥3%) in adult patients receiving celecoxib for migraine: dysgeusia.¹⁶¹

Drug Interactions

Primarily metabolized by CYP2C9.¹

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

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP2C9 inhibitors (e.g., fluconazole): Possible increased celecoxib exposure and toxicity.^{1 161} Celecoxib dosage adjustment may be required.^{1 161}

CYP2C9 inducers (e.g., rifampin): Possible reduced efficacy of celecoxib.^{1 161} Celecoxib dosage adjustment may be required.^{1 161}

CYP2D6 substrates (e.g., atomoxetine): Possible increased exposure to and toxicity of CYP2D6 substrate drugs.^{1 161} Dosage adjustments may be required.¹

Specific Drugs

Celecoxib Pharmacokinetics

Absorption

Bioavailability

Celecoxib capsules: Well absorbed following oral administration; peak plasma concentration usually attained within 3 hours in fasting individuals.¹ Steady-state plasma concentrations achieved within 5 days.¹

Celecoxib oral solution: In fasting individuals, median time to peak plasma concentrations was 1 hour.¹⁶¹

Onset

Single doses of the capsules 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

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

Special Populations

In geriatric patients, peak plasma concentration and AUC increased by 40 and 50%, respectively, after administration as capsules.^{1 161} Peak plasma concentration and AUC were higher in geriatric women than geriatric men, predominantly because of the lower body weight of these women.^{1 161}

In patients with mild or moderate hepatic impairment (Child Pugh Class A or B), AUC of oral capsules increased by 40 or 180%, respectively.^{1 161}

In patients with chronic renal impairment (GFR 35–60 mL/minute), AUC of oral capsules decreased by 40%; pharmacokinetics not studied in patients with severe renal impairment.^{1 161}

AUC of celecoxib is approximately 40% higher in Blacks compared to Caucasians.¹

Distribution

Extent

Distributes into human milk at low levels.^{1 161}

Plasma Protein Binding

97% (principally albumin; α₁-acid glycoprotein to a lesser extent).^{1 161}

Elimination

Metabolism

Metabolized in the liver to inactive metabolites, mainly by CYP2C9.^{1 161}

Elimination Route

Excreted in urine and feces principally as metabolites.^{1 161}

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

Capsules: 11 hours under fasting conditions.¹

Oral solution: Mean apparent elimination half-life approximately 6 hours, independent of dosing conditions; 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

20-25°C (excursions permitted between 15–30°C).¹

Mixture of capsule contents in applesauce is stable for 6 hours when refrigerated.¹

Solution

20–25°C (excursions permitted between 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

Actions

• Selective inhibitor of COX-2.^{1 3 4 5 7 8 10 48 53}

• Differs from nonselective NSAIAs, which inhibit COX-1 and COX-2.^{1 3 4 5 8 11 41}

• Anti-inflammatory, analgesic, and antipyretic actions.^{1 3 9 38 53 60}

• Potential lower risk of GI ulceration than nonselective NSAIAs.^{1 3 9 21 22 24 28 29 38 65 66}

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).^{1 161}

• Advise patients to be alert for symptoms of serious cardiovascular thrombotic events (e.g., MI, stroke).^{1 161} Advise patients to seek immediate medical attention if signs and symptoms of a cardiovascular event (e.g., chest pain, dyspnea, weakness, slurred speech) occur.^{1 161}

• Advise patients to report symptoms of GI ulcerations and bleeding (e.g., epigastric pain, dyspepsia, melena, hematemesis) to their healthcare provider.^{1 161} Inform patients receiving concomitant low-dose aspirin of the increased risk of GI bleeding.^{1 161}

• Inform patients to stop taking celecoxib immediately if they develop any type of rash or fever and to promptly contact their clinician.^{1 161}

• Advise patients to seek emergency medical attention if signs of an anaphylactic reaction occur (e.g., difficulty breathing, swelling of the face or throat).^{1 161}

• Inform patients of the signs and symptoms of hepatotoxicity.^{1 161} Advise patients to discontinue therapy and contact their clinician immediately if signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.^{1 161}

• Inform patients of the risk of heart failure or edema and the importance of reporting dyspnea, unexplained weight gain, or edema.^{1 161}

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.^{1 161} Advise pregnant women to avoid 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.^{1 161}

• Inform women who are trying to conceive that NSAIAs may be associated with a reversible delay in ovulation.^{1 161}

• 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.¹⁶¹

• Advise patients on appropriate administration of celecoxib oral solution for acute treatment of migraine attacks.¹⁶¹

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.^{1 161} 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.^{1 161} Advise patients not to use concomitant low-dose aspirin without consulting their clinician.^{1 161} Alert patients to the presence of NSAIAs in many OTC drugs.^{1 161}

• Advise patients of other important precautionary information.^{1 161}

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

Frequently asked questions

• Is meloxicam very similar to Celebrex?

Medical Disclaimer