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 ). FELDENE® is 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).
INDICATIONS AND USAGE Carefully consider the potential benefits and risks of FELDENE and other treatment options before deciding to use FELDENE. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). FELDENE is indicated: For relief of the signs and symptoms of osteoarthritis. For relief of the signs and symptoms of rheumatoid arthritis.
CONTRAINDICATIONS FELDENE is contraindicated in patients with known hypersensitivity to piroxicam. FELDENE should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS: Anaphylactoid Reactions and PRECAUTIONS: Preexisting Asthma ). FELDENE is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).
ADVERSE REACTIONS In patients taking FELDENE or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1–10% of 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, fluid retention. 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, glomerulonephritis. 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. Reproductive system and breast disorders: Female fertility decreased.
Drug Interactions Highly Protein Bound Drugs FELDENE is highly protein bound and, therefore, might be expected to displace other protein bound drugs. Physicians should closely monitor patients for a change in dosage requirements when administering FELDENE to patients on other highly protein bound drugs. Aspirin When FELDENE is administered with aspirin, its protein binding is reduced, although the clearance of free FELDENE is not altered. Plasma levels of piroxicam are depressed to approximately 80% of their normal values when FELDENE is administered (20 mg/day) in conjunction with aspirin (3900 mg/day). The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of piroxicam and aspirin is not generally recommended because of the potential for increased adverse effects. Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. ACE-Inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE- inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Diuretics Clinical studies, as well as postmarketing observations, have shown that FELDENE can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS: Renal Effects ), as well as to assure diuretic efficacy. Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Warfarin The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Special Populations Pediatric FELDENE has not been investigated in pediatric patients. Race Pharmacokinetic differences due to race have not been identified. Hepatic Insufficiency The effects of hepatic disease on FELDENE pharmacokinetics have not been established. However, a substantial portion of FELDENE elimination occurs by hepatic metabolism. Consequently, patients with hepatic disease may require reduced doses of FELDENE as compared to patients with normal hepatic function. Poor Metabolizers of CYP2C9 Substrates Patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin) should be administered piroxicam with caution as they may have abnormally high plasma levels due to reduced metabolic clearance. Renal Insufficiency FELDENE pharmacokinetics have been investigated in patients with renal insufficiency. Studies indicate patients with mild to moderate renal impairment may not require dosing adjustments. However, the pharmacokinetic properties of FELDENE in patients with severe renal insufficiency or those receiving hemodialysis are not known.