FDA label 442fbcd2-0756-39d6-e054-00144ff88e88

BOXED WARNING Cardiovascular Risk NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS). FELDENEis contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events (see WARNINGS).

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or 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 does increase the risk of serious GI events (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation). Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS). Hypertension NSAIDs, including FELDENE, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including FELDENE, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs. FELDENE should be used with caution in patients with fluid retention or heart failure. Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation NSAIDs, including FELDENE, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3months, and in about 2of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and, therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of FELDENE in patients with advanced renal disease. Therefore, treatment with FELDENE is not recommended in these patients with advanced renal disease. If FELDENE therapy must be initiated, close monitoring of the patient's renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to FELDENE. FELDENE should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONSand PRECAUTIONS: Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including FELDENE, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Other Hypersensitivity Reactions A combination of dermatological and/or allergic signs and symptoms suggestive of serum sickness have occasionally occurred in conjunction with the use of FELDENE. These include arthralgias, pruritus, fever, fatigue, and rash including vesiculobullous reactions and exfoliative dermatitis. Pregnancy In late pregnancy, as with other NSAIDs, FELDENE should be avoided because it may cause premature closure of the ductus arteriosus.

ADVERSE REACTIONS In patients taking FELDENE or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1of patients are: Cardiovascular System:Edema. Digestive System:Anorexia, abdominal pain, constipation, diarrhea, dyspepsia, elevated liver enzymes, flatulence, gross bleeding/perforation, heartburn, nausea, ulcers (gastric/duodenal), vomiting. Hemic and Lymphatic System:Anemia, increased bleeding time. Nervous System:Dizziness, headache. Skin and Appendages:Pruritus, rash. Special Senses:Tinnitus. Urogenital System:Abnormal renal function. Additional adverse experiences reported occasionally include: Body As a Whole:Fever, infection, sepsis. Cardiovascular System:Congestive heart failure, hypertension, tachycardia, syncope. Digestive System:Dry mouth, esophagitis, gastritis, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding, stomatitis. Hemic and Lymphatic System:Ecchymosis, eosinophilia, epistaxis, leukopenia, purpura, petechial rash, thrombocytopenia. Metabolic and Nutritional:Weight changes. Nervous System:Anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo. Respiratory System:Asthma, dyspnea. Skin and Appendages:Alopecia, bruising, desquamation, erythema, photosensitivity, sweat. Special Senses:Blurred vision. Urogenital System:Cystitis, dysuria, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, oliguria/polyuria, proteinuria, renal failure. Other adverse reactions which occur rarely are: Body As a Whole:Anaphylactic reactions, appetite changes, death, flu-like syndrome, pain (colic), serum sickness. Cardiovascular System:Arrhythmia, exacerbation of angina, hypotension, myocardial infarction, palpitations, vasculitis. Digestive System:Eructation, liver failure, pancreatitis. Hemic and Lymphatic System:Agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia. Hypersensitivity:Positive ANA. Metabolic and Nutritional:Hyperglycemia, hypoglycemia. Nervous System:Akathisia, convulsions, coma, hallucinations, meningitis, mood alterations. Respiratory:Respiratory depression, pneumonia. Skin and Appendages:Angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, onycholysis, Stevens-Johnson Syndrome, urticaria, vesiculobullous reaction. Special Senses:Conjunctivitis, hearing impairment, swollen eyes.