Celebrex

— THERAPEUTIC DISORDERS TREATED —
  • Arthritis/rheumatic disorders
  • Dysmenorrhea
  • Nonnarcotic analgesics
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Celebrex Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Celecoxib 50mg, 100mg, 200mg, 400mg; caps.

    Pharmacological Class

    NSAID (COX-2 inhibitor).

    How Supplied

    Caps 100mg, 200mg—100, 500; 50mg, 400mg—60

    How Supplied

    Celebrex 50mg are white, with reverse printed white on red band of body and cap with markings of 7767 on the cap and 50 on the body, supplied in a 60-count bottle.

    Celebrex 100mg are white, with reverse printed white on blue band of body and cap with markings of 7767 on the cap and 100 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 200mg are white, with reverse printed white on gold band with markings of 7767 on the cap and 200 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 400mg are white, with reverse printed white on green band with markings of 7767 on the cap and 400 on the body, supplied in 60-count bottles, and in a carton of 100 unit dose.

     

    Storage

    Store at room temperature 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    Celecoxib has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2.

    Celebrex Indications

    Indications

    Osteoarthritis (OA). Rheumatoid arthritis (RA). Ankylosing spondylitis (AS). Juvenile rheumatoid arthritis (JRA).

    Celebrex Dosage and Administration

    Adult

    Use lowest effective dose for shortest duration. ≥18yrs: OA: 200mg once daily or 100mg twice daily. RA: 100–200mg twice daily. AS: 200mg in 1–2 divided doses; if no response after 6 weeks, 400mg once daily may be tried. <50kg: start at lowest recommended dose. Moderate hepatic impairment, CYP2C9 poor metabolizers: reduce dose by 50%.

    Children

    <2yrs or <10kg: not studied. Use lowest effective dose for shortest duration. May sprinkle capsule contents into applesauce. See full labeling. JRA: ≥2yrs (≥10kg to ≤25kg): 50mg twice daily; (>25kg): 100mg twice daily. CYP2C9 poor metabolizers: consider alternatives.

    Renal Impairment

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Modifications

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Contraindications

    Contraindications

    Sulfonamide, aspirin or other NSAID allergy. Coronary artery bypass graft surgery.

    Celebrex Boxed Warnings

    Boxed Warning

    Risk of serious cardiovascular and gastrointestinal events.

    Boxed Warning

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, with NSAIDs which can be fatal. This risk may occur early in treatment and may increase with duration of use.

    • Celebrex is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. 

    • Greater risk for serious GI events in elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding. 

    Celebrex Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Hypertension; monitor BP closely. Discontinue if signs/symptoms of liver or renal disease develop, or if abnormal liver function tests persist or worsen. Severe hepatic or severe renal impairment: not recommended. Dehydration. Hypovolemia. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, renal, and ocular function in long-term therapy. Pre-existing asthma. Discontinue at 1st sign of skin rash or any other hypersensitivity. May mask signs of infection or fever. Elderly. Debilitated. Labor & delivery. May be associated with a reversible delay in ovulation in females of reproductive potential. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers.

    Warnings/Precautions

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Higher doses showed increased risk for CV thrombotic events. 

    • Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse CV event in NSAID-treated patients. Inform patients about the symptoms of serious CV events and the steps to take if they occur.

    • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as celecoxib, increases the risk of serious gastrointestinal (GI) events.

    • Status Post Coronary Artery Bypass Graft (CABG) Surgery: 

      • NSAIDs are contraindicated in the setting of CABG.

    • Post-MI Patients: 

      • Avoid the use of celecoxib in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. 

      • Monitor for signs of cardiac ischemia if celecoxib is used in patients with a recent MI.

    Gastrointestinal Bleeding, Ulceration, and Perforation 

    • NSAIDs, including celecoxib, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. 

    • Risk Factors for GI Bleeding, Ulceration, and Perforation: 

      • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. 

      • Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. 

      • Fatal GI events occurred mostly in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

    • Strategies to Minimize the GI Risks in NSAID-treated patients:

      • Use the lowest effective dosage for the shortest possible duration. 

      • Avoid administration of more than one NSAID at a time. 

      • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. 

      • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. 

      • Promptly initiate evaluation and treatment if a serious GI adverse event is suspected, and discontinue celecoxib until a serious GI adverse event is ruled out. 

      • Monitor closely for evidence of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. 

    • Inform about the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). 

    • Discontinue celecoxib immediately and perform a clinical evaluation if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.).

    Hypertension

    • NSAIDs, including celecoxib, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Concomitant use with angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may impair response to these therapies when taking NSAIDs. 

    • Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

    Heart Failure and Edema

    • Fluid retention and edema have been observed in some patients treated with NSAIDs. 

    • Celecoxib may blunt the CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).

    • Avoid use in severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. Monitor for signs of worsening heart failure if celecoxib is used in patients with severe heart failure.

    Renal Toxicity and Hyperkalemia

    • Renal Toxicity:

      • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. 

      • Greatest risk seen in patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. 

      • Prior to initiating, correct volume status in dehydrated or hypovolemic patients. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of celecoxib. 

      • Avoid the use of celecoxib in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. 

      • Monitor for signs of worsening renal function if celecoxib is used in patients with advanced renal disease.

    • Hyperkalemia:

      • Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

    Anaphylactic Reactions 

    • Seek emergency help if an anaphylactic reaction occurs. 

    Exacerbation of Asthma Related to Aspirin Sensitivity

    • May have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs.

    • Celecoxib is contraindicated in patients with this form of aspirin sensitivity due to the cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients. 

    • Monitor for changes in the signs and symptoms of asthma when celecoxib is used in patients with preexisting asthma (without known aspirin sensitivity).  

    Serious Skin Reactions

    • NSAIDs, including celecoxib, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. 

    • Discontinue the use of celecoxib at the first appearance of skin rash or any other sign of hypersensitivity. 

    • Celecoxib is contraindicated in patients with previous serious skin reactions to NSAIDs.

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 

    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as celecoxib. Some of these events have been fatal or life-threatening.

    • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. 

    • Discontinue and evaluate the patient immediately if such signs or symptoms are present.

    Fetal Toxicity

    • Premature Closure of Fetal Ductus Arteriosus: 

      • Avoid use of NSAIDS, including celecoxib, in pregnant women at about 30 weeks of gestation and later. NSAIDs, including celecoxib, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. 

    • Oligohydramnios/Neonatal Renal Impairment: 

      • Use of NSAIDs, including celecoxib, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

      • If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit celecoxib use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if celecoxib treatment extends beyond 48 hours. Discontinue celecoxib if oligohydramnios occurs and follow up according to clinical practice.

    Hematologic Toxicity

    • Monitor hemoglobin or hematocrit if signs or symptoms of anemia develop.

    • May increase risk of bleeding events with comorbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor for signs of bleeding.

    Masking of Inflammation and Fever

    • May diminish the utility of diagnostic signs in detecting infections. 

    Laboratory Monitoring

    • Consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically due to serious GI bleeding, hepatotoxicity, and renal injury which may occur without warning symptoms or signs. 

    Disseminated Intravascular Coagulation (DIC)

    • Monitor for signs and symptoms of abnormal clotting or bleeding, and inform patients to report symptoms immediately.

    Pregnancy Considerations

    Risk Summary

    • Use of NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of celecoxib use between about 20 and 30 weeks of gestation, and avoid celecoxib use at about 30 weeks of gestation and later in pregnancy.

    • Premature Closure of Fetal Ductus Arteriosus: Use of NSAIDS, including celecoxib, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

    Clinical Considerations

    • Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If celecoxib treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue celecoxib and follow up according to clinical practice.

    Nursing Mother Considerations

    Risk Summary 

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for celecoxib and any potential adverse effects on the breastfed infant from celecoxib or from the underlying maternal condition.

    Pediatric Considerations

    • Celebrex is approved for the relief of signs/symptoms of Juvenile rheumatoid arthritis in patients 2 years of age and older. The safety and efficacy has not been established beyond 6 months in children. The long-term cardiovascular toxicity in children exposed to Celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex or other COX-2 selective and nonselective NSAIDs.

    • Not studied in patients under 2 years of age, in patients weighing less than 10kg (22lbs), and in patients with active systemic features.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Geriatric Considerations

    • Increased risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. 

    • If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.

    Renal Impairment Considerations

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment Considerations

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Considerations for Specific Populations

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Pharmacokinetics

    Absorption

    • Peak plasma levels: ~3 hours after an oral dose.

    Distribution

    • ~97% protein bound primarily to albumin.

    • Volume of distribution: ~400 L.

    Metabolism

    Hepatic (CYP2C9). 

    Elimination

    • Half-life: 11.2 hours.

    • Eliminated predominantly by hepatic metabolism.

    • Fecal (57%), renal (27%).

    • Plasma clearance: ~500 mL/min.

    Celebrex Interactions

    Interactions

    Avoid concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazide), ACE inhibitors (eg, captopril), ARBs (eg, losartan), or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Caution with CYP2C9 inhibitors (eg, fluconazole), CYP2C9 inducers (eg, rifampin), or drugs that are metabolized by CYP2D6 (eg, atomoxetine).

    Celebrex Adverse Reactions

    Adverse Reactions

    Abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper RTI; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, hypertension, anaphylaxis, anemia, serious skin reactions (eg, erythema multiforme, exfoliative dermatitis, SJS, TEN, DRESS, AGEP); also children: headache, fever, cough.

    Celebrex Clinical Trials

    Clinical Trials

    Osteoarthritis (OA)

    • The efficacy of Celebrex was evaluated for the treatment of the signs/symptoms of OA of the knee and hip in placebo- and active-controlled trial of up to 12 weeks duration. Celebrex 100mg twice daily or 200mg once daily achieved improvement in WOMAC osteoarthritis index, a composite of pain, stiffness, and functional measures in OA.

    • In three 12-week studies of pain accompanying OA flare, Celebrex 100mg twice daily and 200mg twice daily achieved pain reduction within 24 to 48 hours of initiation.

    • Celebrex 100mg twice daily or 200mg twice daily was similar in efficacy to that of naproxen 500mg twice daily. There was no benefit seen with Celebrex 200mg twice daily compared to 100mg twice daily.

    Rheumatoid Arthritis

    • In placebo- and active-controlled trials of up to 24 weeks duration, Celebrex achieved significant reduction in joint tenderness/pain and joint swelling compared with placebo using the ACR20 Responder Index. Celebrex 100mg twice daily or 200mg twice daily was similar in efficacy to that of naproxen 500mg twice daily. Overall efficacy was similar between Celebrex 100mg twice daily and 200mg twice daily, but some patients had additional benefit from the 200mg twice daily dose.

    Juvenile Rheumatoid Arthritis (NCT00652925)

    • The efficacy of Celebrex was evaluated in a 12-week, randomized, double-blind active-controlled, parallel-group, multicenter, non-inferiority study in patients 2 to 17 years of age with pauciarticular, polyarticular course JRA or systemic onset JRA.

    • Patients received either: celecoxib 3 mg/kg (to a maximum of 150 mg) twice daily; celecoxib 6 mg/kg (to a maximum of 300 mg) twice daily; or naproxen 7.5 mg/kg (to a maximum of 500 mg) twice daily.

    • The JRA DOI 30 response rates at week 12 were: 69% for celecoxib 3mg/kg twice daily; 80% for celecoxib 6mg/kg twice daily; and 67% for naproxen 7.5mg/kg twice daily.

    • The safety and efficacy has not been established beyond 6 months in children. The long-term cardiovascular toxicity in children exposed to Celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex or other COX-2 selective and nonselective NSAIDs.

    Ankylosing Spondylitis

    • The efficacy of Celebrex was evaluated in 2 placebo- and active-controlled trials of 6 and 12 weeks duration. 

    • Celebrex 100mg twice daily, 200mg once daily, and 400mg once daily achieved superiority to placebo in these studies for all 3 co-primary efficacy measures assessing global pain intensity (Visual Analogue Scale), global disease activity (Visual Analogue Scale) and functional impairment (Bath Ankylosing Spondylitis Functional Index).

    • There was no difference in improvement between the 200mg and 400mg Celebrex doses in the 12-week study, but a greater proportion of patients treated with Celebrex 400mg responded vs 200mg using the ASAS 20 (53% vs 44%, respectively).

    • Responder analysis also showed no change in the responder rates beyond 6 weeks.

    Cardiovascular Outcomes Trial: Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION; NCT00346216)

    • PRECISION was a long-term non-inferiority trial of 24,081 OA and RA patients designed to assess the cardiovascular safety of celecoxib vs. prescription strength doses of ibuprofen and naproxen. 

    • Results showed that the primary endpoint of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke occurred in 2.3% of celecoxib (100–200mg twice daily) treated individuals compared to 2.5% of the naproxen (375–500mg twice daily) and 2.7% of ibuprofen (600–800mg three times a day) treated individuals. Additionally, the celecoxib group had less serious gastrointestinal events (1.1%) compared to the naproxen (1.5%) and ibuprofen (1.6%) group. 

    Celebrex Note

    Not Applicable

    Celebrex Patient Counseling

    Patient Counseling

    Cardiovascular Thrombotic Events 

    • Be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. 

    • Inform patients of the increased risk for and the signs and symptoms of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms).  Stop taking celecoxib and seek immediate medical therapy if these occur.

    Heart Failure and Edema

    • Be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.

    Anaphylactic Reactions

    • Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Seek immediate emergency help if these occur.

    Serious Skin Reactions, including DRESS 

    • Stop taking celecoxib immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

    Female Fertility

    • Advise females of reproductive potential who desire pregnancy that NSAIDs, including celecoxib, may be associated with a reversible delay in ovulation.

    Fetal Toxicity

    • Avoid use of celecoxib and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with celecoxib is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours.

    Avoid Concomitant Use of NSAIDs

    • Not recommended to use celecoxib with other NSAIDs or salicylates (e.g., diflunisal, salsalate) due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

    Use of NSAIDs and Low-Dose Aspirin

    • Do not use low-dose aspirin concomitantly with celecoxib until they talk to their healthcare provider.

    Cost Savings Program

    Celebrex Savings Card

    Celebrex Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Celecoxib 50mg, 100mg, 200mg, 400mg; caps.

    Pharmacological Class

    NSAID (COX-2 inhibitor).

    How Supplied

    Caps 100mg, 200mg—100, 500; 50mg, 400mg—60

    How Supplied

    Celebrex 50mg are white, with reverse printed white on red band of body and cap with markings of 7767 on the cap and 50 on the body, supplied in a 60-count bottle.

    Celebrex 100mg are white, with reverse printed white on blue band of body and cap with markings of 7767 on the cap and 100 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 200mg are white, with reverse printed white on gold band with markings of 7767 on the cap and 200 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 400mg are white, with reverse printed white on green band with markings of 7767 on the cap and 400 on the body, supplied in 60-count bottles, and in a carton of 100 unit dose.

     

    Storage

    Store at room temperature 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    Celecoxib has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2.

    Celebrex Indications

    Indications

    Dysmenorrhea.

    Celebrex Dosage and Administration

    Adult

    Use lowest effective dose for shortest duration. ≥18yrs: 400mg once then 200mg more on 1st day if needed, then 200mg twice daily. <50kg: start at lowest recommended dose. Moderate hepatic impairment, CYP2C9 poor metabolizers: reduce dose by 50%.

    Children

    <18yrs: not recommended.

    Renal Impairment

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Modifications

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Contraindications

    Contraindications

    Sulfonamide, aspirin or other NSAID allergy. Coronary artery bypass graft surgery.

    Celebrex Boxed Warnings

    Boxed Warning

    Risk of serious cardiovascular and gastrointestinal events.

    Boxed Warning

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, with NSAIDs which can be fatal. This risk may occur early in treatment and may increase with duration of use.

    • Celebrex is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. 

    • Greater risk for serious GI events in elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding. 

    Celebrex Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Hypertension; monitor BP closely. Discontinue if signs/symptoms of liver or renal disease develop, or if abnormal liver function tests persist or worsen. Severe hepatic or severe renal impairment: not recommended. Dehydration. Hypovolemia. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, renal, and ocular function in long-term therapy. Pre-existing asthma. Discontinue at 1st sign of skin rash or any other hypersensitivity. May mask signs of infection or fever. Elderly. Debilitated. Labor & delivery. May be associated with a reversible delay in ovulation in females of reproductive potential. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers.

    Warnings/Precautions

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Higher doses showed increased risk for CV thrombotic events. 

    • Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse CV event in NSAID-treated patients. Inform patients about the symptoms of serious CV events and the steps to take if they occur.

    • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as celecoxib, increases the risk of serious gastrointestinal (GI) events.

    • Status Post Coronary Artery Bypass Graft (CABG) Surgery: 

      • NSAIDs are contraindicated in the setting of CABG.

    • Post-MI Patients: 

      • Avoid the use of celecoxib in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. 

      • Monitor for signs of cardiac ischemia if celecoxib is used in patients with a recent MI.

    Gastrointestinal Bleeding, Ulceration, and Perforation 

    • NSAIDs, including celecoxib, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. 

    • Risk Factors for GI Bleeding, Ulceration, and Perforation: 

      • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. 

      • Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. 

      • Fatal GI events occurred mostly in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

    • Strategies to Minimize the GI Risks in NSAID-treated patients:

      • Use the lowest effective dosage for the shortest possible duration. 

      • Avoid administration of more than one NSAID at a time. 

      • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. 

      • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. 

      • Promptly initiate evaluation and treatment if a serious GI adverse event is suspected, and discontinue celecoxib until a serious GI adverse event is ruled out. 

      • Monitor closely for evidence of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. 

    • Inform about the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). 

    • Discontinue celecoxib immediately and perform a clinical evaluation if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.).

    Hypertension

    • NSAIDs, including celecoxib, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Concomitant use with angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may impair response to these therapies when taking NSAIDs. 

    • Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

    Heart Failure and Edema

    • Fluid retention and edema have been observed in some patients treated with NSAIDs. 

    • Celecoxib may blunt the CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).

    • Avoid use in severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. Monitor for signs of worsening heart failure if celecoxib is used in patients with severe heart failure.

    Renal Toxicity and Hyperkalemia

    • Renal Toxicity:

      • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. 

      • Greatest risk seen in patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. 

      • Prior to initiating, correct volume status in dehydrated or hypovolemic patients. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of celecoxib. 

      • Avoid the use of celecoxib in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. 

      • Monitor for signs of worsening renal function if celecoxib is used in patients with advanced renal disease.

    • Hyperkalemia:

      • Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

    Anaphylactic Reactions 

    • Seek emergency help if an anaphylactic reaction occurs. 

    Exacerbation of Asthma Related to Aspirin Sensitivity

    • May have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs.

    • Celecoxib is contraindicated in patients with this form of aspirin sensitivity due to the cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients. 

    • Monitor for changes in the signs and symptoms of asthma when celecoxib is used in patients with preexisting asthma (without known aspirin sensitivity).  

    Serious Skin Reactions

    • NSAIDs, including celecoxib, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. 

    • Discontinue the use of celecoxib at the first appearance of skin rash or any other sign of hypersensitivity. 

    • Celecoxib is contraindicated in patients with previous serious skin reactions to NSAIDs.

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 

    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as celecoxib. Some of these events have been fatal or life-threatening.

    • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. 

    • Discontinue and evaluate the patient immediately if such signs or symptoms are present.

    Fetal Toxicity

    • Premature Closure of Fetal Ductus Arteriosus: 

      • Avoid use of NSAIDS, including celecoxib, in pregnant women at about 30 weeks of gestation and later. NSAIDs, including celecoxib, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. 

    • Oligohydramnios/Neonatal Renal Impairment: 

      • Use of NSAIDs, including celecoxib, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

      • If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit celecoxib use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if celecoxib treatment extends beyond 48 hours. Discontinue celecoxib if oligohydramnios occurs and follow up according to clinical practice.

    Hematologic Toxicity

    • Monitor hemoglobin or hematocrit if signs or symptoms of anemia develop.

    • May increase risk of bleeding events with comorbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor for signs of bleeding.

    Masking of Inflammation and Fever

    • May diminish the utility of diagnostic signs in detecting infections. 

    Laboratory Monitoring

    • Consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically due to serious GI bleeding, hepatotoxicity, and renal injury which may occur without warning symptoms or signs. 

    Disseminated Intravascular Coagulation (DIC)

    • Monitor for signs and symptoms of abnormal clotting or bleeding, and inform patients to report symptoms immediately.

    Pregnancy Considerations

    Risk Summary

    • Use of NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of celecoxib use between about 20 and 30 weeks of gestation, and avoid celecoxib use at about 30 weeks of gestation and later in pregnancy.

    • Premature Closure of Fetal Ductus Arteriosus: Use of NSAIDS, including celecoxib, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

    Clinical Considerations

    • Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If celecoxib treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue celecoxib and follow up according to clinical practice.

    Nursing Mother Considerations

    Risk Summary 

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for celecoxib and any potential adverse effects on the breastfed infant from celecoxib or from the underlying maternal condition.

    Pediatric Considerations

    • Celebrex is approved for the relief of signs/symptoms of Juvenile rheumatoid arthritis in patients 2 years of age and older. The safety and efficacy has not been established beyond 6 months in children. The long-term cardiovascular toxicity in children exposed to Celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex or other COX-2 selective and nonselective NSAIDs.

    • Not studied in patients under 2 years of age, in patients weighing less than 10kg (22lbs), and in patients with active systemic features.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Geriatric Considerations

    • Increased risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. 

    • If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.

    Renal Impairment Considerations

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment Considerations

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Considerations for Specific Populations

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Pharmacokinetics

    Absorption

    • Peak plasma levels: ~3 hours after an oral dose.

    Distribution

    • ~97% protein bound primarily to albumin.

    • Volume of distribution: ~400 L.

    Metabolism

    Hepatic (CYP2C9). 

    Elimination

    • Half-life: 11.2 hours.

    • Eliminated predominantly by hepatic metabolism.

    • Fecal (57%), renal (27%).

    • Plasma clearance: ~500 mL/min.

    Celebrex Interactions

    Interactions

    Avoid concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazide), ACE inhibitors (eg, captopril), ARBs (eg, losartan), or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Caution with CYP2C9 inhibitors (eg, fluconazole), CYP2C9 inducers (eg, rifampin), or drugs that are metabolized by CYP2D6 (eg, atomoxetine).

    Celebrex Adverse Reactions

    Adverse Reactions

    Abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper RTI; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, hypertension, anaphylaxis, anemia, serious skin reactions (eg, erythema multiforme, exfoliative dermatitis, SJS, TEN, DRESS, AGEP).

    Celebrex Clinical Trials

    Clinical Trials

    Analgesia, including Primary Dysmenorrhea

    • Celebrex achieved pain relief in acute analgesic models of post-oral surgery pain, post-orthopedic surgical pain, and primary dysmenorrhea.

    • Single doses of Celebrex achieved pain relief within 60 minutes.

    Celebrex Note

    Not Applicable

    Celebrex Patient Counseling

    Patient Counseling

    Cardiovascular Thrombotic Events 

    • Be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. 

    • Inform patients of the increased risk for and the signs and symptoms of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms).  Stop taking celecoxib and seek immediate medical therapy if these occur.

    Heart Failure and Edema

    • Be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.

    Anaphylactic Reactions

    • Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Seek immediate emergency help if these occur.

    Serious Skin Reactions, including DRESS 

    • Stop taking celecoxib immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

    Female Fertility

    • Advise females of reproductive potential who desire pregnancy that NSAIDs, including celecoxib, may be associated with a reversible delay in ovulation.

    Fetal Toxicity

    • Avoid use of celecoxib and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with celecoxib is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours.

    Avoid Concomitant Use of NSAIDs

    • Not recommended to use celecoxib with other NSAIDs or salicylates (e.g., diflunisal, salsalate) due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

    Use of NSAIDs and Low-Dose Aspirin

    • Do not use low-dose aspirin concomitantly with celecoxib until they talk to their healthcare provider.

    Cost Savings Program

    Celebrex Savings Card

    Celebrex Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Celecoxib 50mg, 100mg, 200mg, 400mg; caps.

    Pharmacological Class

    NSAID (COX-2 inhibitor).

    How Supplied

    Caps 100mg, 200mg—100, 500; 50mg, 400mg—60

    How Supplied

    Celebrex 50mg are white, with reverse printed white on red band of body and cap with markings of 7767 on the cap and 50 on the body, supplied in a 60-count bottle.

    Celebrex 100mg are white, with reverse printed white on blue band of body and cap with markings of 7767 on the cap and 100 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 200mg are white, with reverse printed white on gold band with markings of 7767 on the cap and 200 on the body, supplied in 100- and 500-count bottles, and in a carton of 100 unit dose.

    Celebrex 400mg are white, with reverse printed white on green band with markings of 7767 on the cap and 400 on the body, supplied in 60-count bottles, and in a carton of 100 unit dose.

     

    Storage

    Store at room temperature 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    Celecoxib has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2.

    Celebrex Indications

    Indications

    Acute pain.

    Celebrex Dosage and Administration

    Adult

    Use lowest effective dose for shortest duration. ≥18yrs: 400mg once then 200mg more on 1st day if needed, then 200mg twice daily. <50kg: start at lowest recommended dose. Moderate hepatic impairment, CYP2C9 poor metabolizers: reduce dose by 50%.

    Children

    <18yrs: not recommended.

    Renal Impairment

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Modifications

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Contraindications

    Contraindications

    Sulfonamide, aspirin or other NSAID allergy. Coronary artery bypass graft surgery.

    Celebrex Boxed Warnings

    Boxed Warning

    Risk of serious cardiovascular and gastrointestinal events.

    Boxed Warning

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, with NSAIDs which can be fatal. This risk may occur early in treatment and may increase with duration of use.

    • Celebrex is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. 

    • Greater risk for serious GI events in elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding. 

    Celebrex Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Hypertension; monitor BP closely. Discontinue if signs/symptoms of liver or renal disease develop, or if abnormal liver function tests persist or worsen. Severe hepatic or severe renal impairment: not recommended. Dehydration. Hypovolemia. Hyperkalemia. Coagulation disorders. Monitor CBCs, blood chemistry, hepatic, renal, and ocular function in long-term therapy. Pre-existing asthma. Discontinue at 1st sign of skin rash or any other hypersensitivity. May mask signs of infection or fever. Elderly. Debilitated. Labor & delivery. May be associated with a reversible delay in ovulation in females of reproductive potential. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers.

    Warnings/Precautions

    Cardiovascular Thrombotic Events 

    • Increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Higher doses showed increased risk for CV thrombotic events. 

    • Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse CV event in NSAID-treated patients. Inform patients about the symptoms of serious CV events and the steps to take if they occur.

    • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as celecoxib, increases the risk of serious gastrointestinal (GI) events.

    • Status Post Coronary Artery Bypass Graft (CABG) Surgery: 

      • NSAIDs are contraindicated in the setting of CABG.

    • Post-MI Patients: 

      • Avoid the use of celecoxib in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. 

      • Monitor for signs of cardiac ischemia if celecoxib is used in patients with a recent MI.

    Gastrointestinal Bleeding, Ulceration, and Perforation 

    • NSAIDs, including celecoxib, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. 

    • Risk Factors for GI Bleeding, Ulceration, and Perforation: 

      • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. 

      • Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. 

      • Fatal GI events occurred mostly in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

    • Strategies to Minimize the GI Risks in NSAID-treated patients:

      • Use the lowest effective dosage for the shortest possible duration. 

      • Avoid administration of more than one NSAID at a time. 

      • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. 

      • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. 

      • Promptly initiate evaluation and treatment if a serious GI adverse event is suspected, and discontinue celecoxib until a serious GI adverse event is ruled out. 

      • Monitor closely for evidence of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. 

    • Inform about the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). 

    • Discontinue celecoxib immediately and perform a clinical evaluation if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.).

    Hypertension

    • NSAIDs, including celecoxib, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Concomitant use with angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may impair response to these therapies when taking NSAIDs. 

    • Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

    Heart Failure and Edema

    • Fluid retention and edema have been observed in some patients treated with NSAIDs. 

    • Celecoxib may blunt the CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).

    • Avoid use in severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. Monitor for signs of worsening heart failure if celecoxib is used in patients with severe heart failure.

    Renal Toxicity and Hyperkalemia

    • Renal Toxicity:

      • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. 

      • Greatest risk seen in patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. 

      • Prior to initiating, correct volume status in dehydrated or hypovolemic patients. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of celecoxib. 

      • Avoid the use of celecoxib in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. 

      • Monitor for signs of worsening renal function if celecoxib is used in patients with advanced renal disease.

    • Hyperkalemia:

      • Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

    Anaphylactic Reactions 

    • Seek emergency help if an anaphylactic reaction occurs. 

    Exacerbation of Asthma Related to Aspirin Sensitivity

    • May have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs.

    • Celecoxib is contraindicated in patients with this form of aspirin sensitivity due to the cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients. 

    • Monitor for changes in the signs and symptoms of asthma when celecoxib is used in patients with preexisting asthma (without known aspirin sensitivity).  

    Serious Skin Reactions

    • NSAIDs, including celecoxib, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. 

    • Discontinue the use of celecoxib at the first appearance of skin rash or any other sign of hypersensitivity. 

    • Celecoxib is contraindicated in patients with previous serious skin reactions to NSAIDs.

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 

    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as celecoxib. Some of these events have been fatal or life-threatening.

    • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. 

    • Discontinue and evaluate the patient immediately if such signs or symptoms are present.

    Fetal Toxicity

    • Premature Closure of Fetal Ductus Arteriosus: 

      • Avoid use of NSAIDS, including celecoxib, in pregnant women at about 30 weeks of gestation and later. NSAIDs, including celecoxib, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. 

    • Oligohydramnios/Neonatal Renal Impairment: 

      • Use of NSAIDs, including celecoxib, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

      • If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit celecoxib use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if celecoxib treatment extends beyond 48 hours. Discontinue celecoxib if oligohydramnios occurs and follow up according to clinical practice.

    Hematologic Toxicity

    • Monitor hemoglobin or hematocrit if signs or symptoms of anemia develop.

    • May increase risk of bleeding events with comorbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor for signs of bleeding.

    Masking of Inflammation and Fever

    • May diminish the utility of diagnostic signs in detecting infections. 

    Laboratory Monitoring

    • Consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically due to serious GI bleeding, hepatotoxicity, and renal injury which may occur without warning symptoms or signs. 

    Disseminated Intravascular Coagulation (DIC)

    • Monitor for signs and symptoms of abnormal clotting or bleeding, and inform patients to report symptoms immediately.

    Pregnancy Considerations

    Risk Summary

    • Use of NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of celecoxib use between about 20 and 30 weeks of gestation, and avoid celecoxib use at about 30 weeks of gestation and later in pregnancy.

    • Premature Closure of Fetal Ductus Arteriosus: Use of NSAIDS, including celecoxib, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

    Clinical Considerations

    • Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including celecoxib, can cause premature closure of the fetal ductus arteriosus.

    • Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If celecoxib treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue celecoxib and follow up according to clinical practice.

    Nursing Mother Considerations

    Risk Summary 

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for celecoxib and any potential adverse effects on the breastfed infant from celecoxib or from the underlying maternal condition.

    Pediatric Considerations

    • Celebrex is approved for the relief of signs/symptoms of Juvenile rheumatoid arthritis in patients 2 years of age and older. The safety and efficacy has not been established beyond 6 months in children. The long-term cardiovascular toxicity in children exposed to Celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex or other COX-2 selective and nonselective NSAIDs.

    • Not studied in patients under 2 years of age, in patients weighing less than 10kg (22lbs), and in patients with active systemic features.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Geriatric Considerations

    • Increased risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. 

    • If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.

    Renal Impairment Considerations

    • Severe renal insufficiency: not recommended.

    Hepatic Impairment Considerations

    • Moderate hepatic impairment (Child-Pugh B): reduce dose by 50%.

    • Severe hepatic impairment: not recommended.

    Other Considerations for Specific Populations

    Females and Males of Reproductive Potential

    • Infertility for Females: May delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawal of NSAIDs, including celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility.

     Poor Metabolizers of CYP2C9 Substrates

    • Known or suspected poor CYP2C19 metabolizers: give Celebrex starting with half the lowest recommended dose.

    • Consider alternative therapies for the treatment of JRA in pediatric patients who are CYP2C19 poor metabolizers.

    Celebrex Pharmacokinetics

    Absorption

    • Peak plasma levels: ~3 hours after an oral dose.

    Distribution

    • ~97% protein bound primarily to albumin.

    • Volume of distribution: ~400 L.

    Metabolism

    Hepatic (CYP2C9). 

    Elimination

    • Half-life: 11.2 hours.

    • Eliminated predominantly by hepatic metabolism.

    • Fecal (57%), renal (27%).

    • Plasma clearance: ~500 mL/min.

    Celebrex Interactions

    Interactions

    Avoid concomitant aspirin, salicylates (eg, diflunisal, salsalate) or other NSAIDs. Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazide), ACE inhibitors (eg, captopril), ARBs (eg, losartan), or β-blockers; monitor closely. Potentiates digoxin; monitor levels. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity. Caution with CYP2C9 inhibitors (eg, fluconazole), CYP2C9 inducers (eg, rifampin), or drugs that are metabolized by CYP2D6 (eg, atomoxetine).

    Celebrex Adverse Reactions

    Adverse Reactions

    Abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper RTI; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, hypertension, anaphylaxis, anemia, serious skin reactions (eg, erythema multiforme, exfoliative dermatitis, SJS, TEN, DRESS, AGEP).

    Celebrex Clinical Trials

    Clinical Trials

    Osteoarthritis (OA)

    • The efficacy of Celebrex was evaluated for the treatment of the signs/symptoms of OA of the knee and hip in placebo- and active-controlled trial of up to 12 weeks duration. Celebrex 100mg twice daily or 200mg once daily achieved improvement in WOMAC osteoarthritis index, a composite of pain, stiffness, and functional measures in OA.

    • In three 12-week studies of pain accompanying OA flare, Celebrex 100mg twice daily and 200mg twice daily achieved pain reduction within 24 to 48 hours of initiation.

    • Celebrex 100mg twice daily or 200mg twice daily was similar in efficacy to that of naproxen 500mg twice daily. There was no benefit seen with Celebrex 200mg twice daily compared to 100mg twice daily.

    Rheumatoid Arthritis

    • In placebo- and active-controlled trials of up to 24 weeks duration, Celebrex achieved significant reduction in joint tenderness/pain and joint swelling compared with placebo using the ACR20 Responder Index. Celebrex 100mg twice daily or 200mg twice daily was similar in efficacy to that of naproxen 500mg twice daily. Overall efficacy was similar between Celebrex 100mg twice daily and 200mg twice daily, but some patients had additional benefit from the 200mg twice daily dose.

    Juvenile Rheumatoid Arthritis (NCT00652925)

    • The efficacy of Celebrex was evaluated in a 12-week, randomized, double-blind active-controlled, parallel-group, multicenter, non-inferiority study in patients 2 to 17 years of age with pauciarticular, polyarticular course JRA or systemic onset JRA.

    • Patients received either: celecoxib 3 mg/kg (to a maximum of 150 mg) twice daily; celecoxib 6 mg/kg (to a maximum of 300 mg) twice daily; or naproxen 7.5 mg/kg (to a maximum of 500 mg) twice daily.

    • The JRA DOI 30 response rates at week 12 were: 69% for celecoxib 3mg/kg twice daily; 80% for celecoxib 6mg/kg twice daily; and 67% for naproxen 7.5mg/kg twice daily.

    • The safety and efficacy has not been established beyond 6 months in children. The long-term cardiovascular toxicity in children exposed to Celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to Celebrex or other COX-2 selective and nonselective NSAIDs.

    Ankylosing Spondylitis

    • The efficacy of Celebrex was evaluated in 2 placebo- and active-controlled trials of 6 and 12 weeks duration. 

    • Celebrex 100mg twice daily, 200mg once daily, and 400mg once daily achieved superiority to placebo in these studies for all 3 co-primary efficacy measures assessing global pain intensity (Visual Analogue Scale), global disease activity (Visual Analogue Scale) and functional impairment (Bath Ankylosing Spondylitis Functional Index).

    • There was no difference in improvement between the 200mg and 400mg Celebrex doses in the 12-week study, but a greater proportion of patients treated with Celebrex 400mg responded vs 200mg using the ASAS 20 (53% vs 44%, respectively).

    • Responder analysis also showed no change in the responder rates beyond 6 weeks.

    Cardiovascular Outcomes Trial: Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION; NCT00346216)

    • PRECISION was a long-term non-inferiority trial of 24,081 OA and RA patients designed to assess the cardiovascular safety of celecoxib vs. prescription strength doses of ibuprofen and naproxen. 

    • Results showed that the primary endpoint of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke occurred in 2.3% of celecoxib (100–200mg twice daily) treated individuals compared to 2.5% of the naproxen (375–500mg twice daily) and 2.7% of ibuprofen (600–800mg three times a day) treated individuals. Additionally, the celecoxib group had less serious gastrointestinal events (1.1%) compared to the naproxen (1.5%) and ibuprofen (1.6%) group. 

    Celebrex Note

    Not Applicable

    Celebrex Patient Counseling

    Patient Counseling

    Cardiovascular Thrombotic Events 

    • Be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately.

    Gastrointestinal Bleeding, Ulceration, and Perforation

    • Report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. 

    • Inform patients of the increased risk for and the signs and symptoms of GI bleeding in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis.

    Hepatotoxicity

    • Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms).  Stop taking celecoxib and seek immediate medical therapy if these occur.

    Heart Failure and Edema

    • Be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.

    Anaphylactic Reactions

    • Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Seek immediate emergency help if these occur.

    Serious Skin Reactions, including DRESS 

    • Stop taking celecoxib immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible.

    Female Fertility

    • Advise females of reproductive potential who desire pregnancy that NSAIDs, including celecoxib, may be associated with a reversible delay in ovulation.

    Fetal Toxicity

    • Avoid use of celecoxib and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with celecoxib is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours.

    Avoid Concomitant Use of NSAIDs

    • Not recommended to use celecoxib with other NSAIDs or salicylates (e.g., diflunisal, salsalate) due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

    Use of NSAIDs and Low-Dose Aspirin

    • Do not use low-dose aspirin concomitantly with celecoxib until they talk to their healthcare provider.

    Cost Savings Program

    Celebrex Savings Card

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