Important Safety Information and Indications

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in the 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

  • NSAIDs cause an 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. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious (GI) events

Use CELEBREX at the lowest dose for the shortest duration possible to minimize risk of CV, GI and hepatic adverse events.

Contraindications

  • Known hypersensitivity to celecoxib or any components of the drug product or sulfonamides
  • History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
  • In the setting of CABG surgery

Warnings and Precautions

Post-MI Patients: Avoid the use of CELEBREX in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If CELEBREX is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Hepatotoxicity: Elevations of ALT or AST have been reported in patients with NSAIDs. In addition, rare, sometimes fatal cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop.

Hypertension: NSAIDs, including CELEBREX, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure.

Heart Failure and Edema: Avoid the use of CELEBREX in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If CELEBREX is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Renal Toxicity: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury and may cause a dose-dependent reduction in prostaglandin formation, which may precipitate overt renal decompensation. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of CELEBREX in patients with advanced renal disease unless benefits are expected to outweigh the risk of worsening renal function. If CELEBREX is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.

Anaphylactic Reactions: Celecoxib has been associated with anaphylactic reactions in patients with and without known hypersensitivity to celecoxib and in patients with aspirin-sensitive asthma. CELEBREX is a sulfonamide and both NSAIDs and sulfonamides may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

Exacerbation of Asthma Related to Aspirin Sensitivity: CELEBREX is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity).

Serious Skin Reactions: Serious skin reactions have occurred following treatment with CELEBREX, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). These serious events may occur without warning and can be fatal. Discontinue CELEBREX at first appearance of skin rash or other signs of hypersensitivity.

Premature Closure of Fetal Ductus Arteriosus: Celecoxib may cause premature closure of the ductus arteriosus. Avoid use of NSAIDs, including CELEBREX, in pregnant women starting at 30 weeks of gestation (third trimester).

Hematologic Toxicity: Anemia has occurred in NSAID treatment patients. Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia. NSAIDs, including CELEBREX, may increase the risk of bleeding events. Monitor patients for signs of bleeding.

Disseminated Intravascular Coagulation (DIC): Because of the risk of disseminated intravascular coagulation with use of CELEBREX in pediatric patients with systemic onset JRA, monitor patients for signs and symptoms of abnormal clotting or bleeding, and inform patients and their caregivers to report symptoms as soon as possible.

Drug Interactions

Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking CELEBREX with drugs that interfere with hemostasis. Concomitant use of CELEBREX and analgesic dose of aspirin is not generally recommended.

ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers: Concomitant use with CELEBREX may diminish the antihypertensive effect of these drugs. Monitor blood pressure.

ACE Inhibitors and ARBs: Concomitant use with CELEBREX in the elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high risk patients, monitor for signs of worsening renal function.

Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects.

Digoxin: Concomitant use with CELEBREX can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels.

Adverse Reactions: The most common adverse reactions in arthritis trials (>2% and >placebo) are: abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, rash.

Use in Specific Populations

Pregnancy: Use of NSAIDs during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs in pregnant women starting at 30 weeks of gestation.

Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of CELEBREX in women who have difficulties conceiving.

Please see Full Prescribing Information including BOXED WARNING and Medication Guide.

Indications

CELEBREX is indicated for the management of the signs and symptoms of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis in patients 2 years and older, and ankylosing spondylitis; for the management of acute pain in adults, and for the management of primary dysmenorrhea.

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Acute Pain

See data about CELEBREX and the Oxford Knee Score, an overall measure of knee pain and function

In the same study,

CELEBREX helped improve Oxford Knee Score,* an overall measure of pain and function, at week 61,2

*Oxford Knee Score is a 12-item questionnaire which provides an overall measure (score 12-60) of patient's assessment of pain and function post-TKA.2
References: 1. Schroer WC, Diesfeld PJ, LeMarr AR, Reedy ME. Benefits of prolonged postoperative cyclooxygenase-2 inhibitor administration on total knee arthroplasty recovery: a double-blind, placebo-controlled study. J Arthroplasty. 2011;26(6 suppl):2-7. 2. Dawson J, Fitzpatrick R, Murray D, Carr A. Questionnaire on the perceptions of patients about total knee replacement. J Bone Joint Surg. 1998;80-B(1):63-69.

Study Descriptions

Schroer et al was a randomized, double-blind, placebo-controlled study in patients undergoing elective unilateral total knee arthroplasty (TKA) to evaluate any rehabilitation benefits of CELEBREX therapy for 6 weeks after the TKA (N=107). CELEBREX 400 mg was given to each patient before surgery and daily throughout their hospitalization with as needed morphine through a patient-controlled analgesia system on the night of surgery. All patients were placed on oral narcotics the morning after surgery. At hospital discharge, patients were randomized to either CELEBREX 200 mg BID or placebo for 6 weeks. All patients had a prescription for oral narcotics as needed. Primary end point was narcotic use (total pill count), and secondary measures included knee pain during activity and at rest, as measured by a visual analog scale (VAS), and Oxford Knee Score.

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Ekman et al (2006) was a 36-hour, randomized, parallel-group, double-blind, placebo-controlled study to compare total opioid analgesic use at 24 hours after arthroscopic meniscectomy of the knee (primary end point). Patients received CELEBREX 400 mg administered approximately 1 hour before surgery and CELEBREX 200 mg administered at the first request for pain medication after surgery, or placebo. Postsurgery patients were allowed to take 1 to 2 hydrocodone/acetaminophen (APAP) tablets every 4 to 6 hours as rescue medication. Secondary end points included patients' assessment of pain at rest and at 90° flexion using a 0- to 100-mm visual analog scale (VAS). Improvement in patients' assessment of pain at 90° flexion at 8, 10, and 12 hours confirmed in a replicate study. CELEBREX significantly reduced postsurgical knee pain at rest at 10 and 12 hours in the same 2 studies.

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Ekman et al (2002) was a 10-day, multicenter, double-blind, randomized, parallel-group, placebo-controlled trial to evaluate the efficacy and tolerability of CELEBREX, ibuprofen, or placebo in the treatment of moderate-to-severe acute pain (at least 45 mm on a 100-mm VAS) in 445 adult patients with grade 1 or grade 2 ankle sprain. Patients were randomized to CELEBREX 200 mg BID, ibuprofen 800 mg TID, or placebo. The first dose of study medication was taken as soon as possible after randomization and within 48 hours of injury. Treatment with rest, ice, compression, and elevation (RICE) and physical therapy was permitted; analgesia other than the study medication was not. The study was powered to detect differences between CELEBREX and placebo and to establish noninferiority vs ibuprofen. Primary end points (evaluated on day 4) were pain rating using the patient's assessment of ankle pain on a visual analog scale (VAS) and severity based on the patient's global assessment of ankle injury. Secondary end points included: pain rating using the patient's assessment of ankle pain on a VAS on days 8 and 11; severity based on the patient's global assessment of ankle injury on days 8 and 11; median time to return to normal function/activity or to improve by at least 2 grades.

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*Eligibility required. Terms and conditions apply. Card will be accepted only at participating pharmacies. Card is not health insurance. No membership fee. Savings of up to $125 per fill for a maximum savings of up to $1,750 per year. For more information, visit www.Celebrex.com, call 1-855-612-1956, or write: CELEBREX Savings Card, 2250 Perimeter Park Drive, Suite 300, Morrisville, NC 27560.

References:

1. Schroer WC, Diesfeld PJ, LeMarr AR, Reedy ME. Benefits of prolonged postoperative cyclooxygenase-2 inhibitor administration on total knee arthroplasty recovery: a double-blind, placebo-controlled study. J Arthroplasty. 2011;26(6 suppl):2-7.

2. Ekman EF, Wahba M, Ancona F. Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery: a double-blind, placebo-controlled study. Arthroscopy. 2006;22(6):635-642.

3. Data on file. Pfizer Inc, New York, NY.

4. Ekman EF, Fiechtner JJ, Levy S, Fort JG. Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain. Am J Orthop. 2002;31(8):445-451.

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