Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have a CBC and a chemistry profile checked periodically. If abnormal liver tests or renal tests persist or worsen, CELEBREX should be discontinued.
In controlled clinical trials, elevated BUN occurred more frequently in patients receiving CELEBREX compared with patients on placebo. This laboratory abnormality was also seen in patients who received comparator NSAIDs in these studies. The clinical significance of this abnormality has not been established.
The pharmacological activity of CELEBREX in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting infectious complications of presumed noninfectious, painful conditions.
The concomitant use of CELEBREX with any dose of a non-aspirin NSAID should be avoided due to the potential for increased risk of adverse reactions.
Of the CELEBREX-treated patients in the pre-marketing controlled clinical trials, approximately 4,250 were patients with OA, approximately 2,100 were patients with RA, and approximately 1,050 were patients with post-surgical pain. More than 8,500 patients received a total daily dose of CELEBREX of 200 mg (100 mg twice daily or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg twice daily). Approximately 3,900 patients received CELEBREX at these doses for 6 months or more; approximately 2,300 of these have received it for 1 year or more and 124 of these have received it for 2 years or more.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Table 1 lists all adverse events, regardless of causality, occurring in ≥2% of patients receiving CELEBREX from 12 controlled studies conducted in patients with OA or RA that included a placebo and/or a positive control group. Since these 12 trials were of different durations, and patients in the trials may not have been exposed for the same duration of time, these percentages do not capture cumulative rates of occurrence.
|CBX = CELEBREX 100 – 200 mg twice daily or 200 mg once daily;NAP = Naproxen 500 mg twice daily;DCF = Diclofenac 75 mg twice daily;IBU = Ibuprofen 800 mg three times daily.|
|Body as a whole|
|Central, Peripheral Nervous system|
|Upper Respiratory Infection||8.1%||6.7%||9.9%||9.8%||9.9%|
In placebo- or active-controlled clinical trials, the discontinuation rate due to adverse events was 7.1% for patients receiving CELEBREX and 6.1% for patients receiving placebo. Among the most common reasons for discontinuation due to adverse events in the CELEBREX treatment groups were dyspepsia and abdominal pain (cited as reasons for discontinuation in 0.8% and 0.7% of CELEBREX patients, respectively). Among patients receiving placebo, 0.6% discontinued due to dyspepsia and 0.6% withdrew due to abdominal pain.
The following adverse reactions occurred in 0.1 – 1.9% of patients treated with CELEBREX (100 – 200 mg twice daily or 200 mg once daily):
|Gastrointestinal :||Constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, dry mouth, stomatitis, tenesmus, vomiting|
|Cardiovascular:||Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction|
|General :||Allergy aggravated, allergic reaction, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain|
|Central, peripheral nervous system:||Leg cramps, hypertonia, hypoesthesia, migraine, paresthesia, vertigo|
|Hearing and vestibular :||Deafness, tinnitus|
|Heart rate and rhythm :||Palpitation, tachycardia|
|Liver and biliary :||Hepatic function abnormal, SGOT increased, SGPT increased|
|Metabolic and nutritional :||BUN increased, CPK increased, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increased, creatinine increased, alkaline phosphatase increased, weight increased|
|Musculoskeletal :||Arthralgia, arthrosis, myalgia, synovitis, tendinitis|
|Platelets (bleeding or clotting) :||Ecchymosis, epistaxis, thrombocythemia|
|Psychiatric :||Anorexia, anxiety, appetite increased, depression, nervousness, somnolence|
|Respiratory :||Bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea, laryngitis, pneumonia|
|Skin and appendages :||Alopecia, dermatitis, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, urticaria|
|Application site disorders :||Cellulitis, dermatitis contact|
|Urinary :||Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus|
The following serious adverse events (causality not evaluated) occurred in <0.1% of patients (cases reported only in post-marketing experience are indicated in italics):
|Cardiovascular :||Syncope, congestive heart failure, ventricular fibrillation, pulmonary embolism, cerebrovascular accident, peripheral gangrene, thrombophlebitis, vasculitis, deep venous thrombosis|
|Gastrointestinal :||Intestinal obstruction, intestinal perforation, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, pancreatitis, ileus|
|Liver and biliary :||Cholelithiasis, hepatitis, jaundice, liver failure|
|Hemic and lymphatic :||Thrombocytopenia, agranulocytosis,aplastic anemia, pancytopenia, leucopenia|
|Nervous :||Ataxia, suicide, aseptic meningitis, ageusia, anosmia, fatal intracranial hemorrhage [see Drug Interactions (7.1)]|
|Renal :||Acute renal failure, interstitial nephritis|
|Skin:||Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis|
|General :||Sepsis, sudden death, anaphylactoid reaction, angioedema|
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