Piroxicam

Piroxicam Capsules are indicated: For relief of the signs and symptoms of osteoarthritis. For relief of the signs and symptoms of rheumatoid arthritis.

Carefully consider the potential benefits and risks of Piroxicam Capsules and other treatment options before deciding to use Piroxicam Capsules. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)]. After observing the response to initial therapy with Piroxicam Capsules, the dose and frequency should be adjusted to suit an individual patient's needs. For the relief of rheumatoid arthritis and osteoarthritis, the dosage is 20 mg given orally once per day. If desired, the daily dose may be divided. Because of the long half-life of Piroxicam Capsules, steady-state blood levels are not reached for 7 to 12 days. Therefore, although the therapeutic effects of Piroxicam Capsules are evident early in treatment, there is a progressive increase in response over several weeks and the effect of therapy should not be assessed for two weeks.

5.1 Cardiovascular Thrombotic Events Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, 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. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed 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 piroxicam, increases the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications (4)]. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of Piroxicam Capsules in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Piroxicam Capsules are used in patients with a recent MI, monitor patients for signs of cardiac ischemia. 5.2 Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs, including piroxicam capsules, 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. 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 occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. However, even short-term NSAID therapy is not without risk. 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…

Piroxicam Capsules are contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to piroxicam or any components of the drug product [see Warnings and Precautions (5.7, 5.9)] History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.8)] In the setting of CABG surgery [see Warnings and Precautions (5.1)]

See Table 1 for clinically significant drug interactions with piroxicam. Table 1: Clinically Significant Drug Interactions with Piroxicam Drugs That Interfere with Hemostasis Clinical Impact: • Piroxicam and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of piroxicam and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. • Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of Piroxicam Capsules with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see Warnings and Precautions (5.12)]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions (5.2)]. Intervention: Concomitant use of Piroxicam Capsules and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions (5.12)]. Piroxicam Capsules are not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: • NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers (including propranolol). • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention: • During concomitant use of Piroxicam Capsules and ACE inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. • During concomitant use of Piroxicam Capsules and ACE inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions (5.6)]. • When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of Piroxicam Capsules with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6)]. Digoxin Clinical Impact: The concomitant use of piroxicam with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention: During concomitant use of Piroxicam Capsules and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of Piroxicam Capsules and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinica…

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)] Hepatotoxicity [see Warnings and Precautions (5.3)] Hypertension [see Warnings and Precautions (5.4)] Heart Failure and Edema [see Warnings and Precautions (5.5)] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)] Anaphylactic Reactions [see Warnings and Precautions (5.7)] Serious Skin Reactions [see Warnings and Precautions (5.9)] Hematologic Toxicity [see Warnings and Precautions (5.12)] 6.1 Clinical Trials Experience 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. In patients taking Piroxicam Capsules or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1% to 10% of patients are: Cardiovascular System: Edema Digestive System: Anorexia, abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting Nervous System: Dizziness, headache, vertigo Skin and Appendages: Pruritus, rash Special Senses: Tinnitus Additional adverse experiences reported occasionally include: Cardiovascular System: Palpitations Digestive System: Stomatitis Nervous System: Drowsiness Special Senses: Blurred vision 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Piroxicam Capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: Fever, infection, sepsis, anaphylactic reactions, appetite changes, death, flu-like syndrome, pain (colic), serum sickness Cardiovascular System: Congestive heart failure, hypertension, tachycardia, syncope, arrhythmia, exacerbation of angina, hypotension, myocardial infarction, vasculitis Digestive System: Dyspepsia, elevated liver enzymes, gross bleeding/perforation, heartburn, ulcers (gastric/duodenal), dry mouth, esophagitis, gastritis, glossitis, hematemesis, hepatitis, jaundice, melena, rectal bleeding, eructation, liver failure, pancreatitis Hemic and Lymphatic System: Anemia, increased bleeding time, ecchymosis, eosinophilia, epistaxis, leukopenia, purpura, petechial rash, thrombocytopenia, agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia Hypersensitivity: Positive ANA Metabolic and Nutritional: Weight changes, Fluid retention, hyperglycemia, hypoglycemia Nervous System: Anxiety, asthenia, confusion, depression, dream abnormalities, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, akathisia, convulsions, coma, hallucinations, meningitis, mood alterations Respiratory System: Asthma, dyspnea, respiratory depression, pneumonia Skin and Appendages: Alopecia, bruising, desquamation, erythema, photosensitivity, sweat, angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, onycholysis, Stevens Johnson Syndrome, urticaria, vesiculobullous reaction Special Senses: Conjunctivitis, hearing impairment, swollen eyes Urogenital System: Abnormal renal function, cystitis, dysuria, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, oliguria/polyuria, proteinuria, renal failure, glomerulonephritis Reproductive System and Breast Disorders: Female fertility decreased