FDA label 6e5b8c85-b0c4-4864-b7e6-e6c63b144009

PRESCRIBING INFORMATION 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 and CLINICAL TRIALS). Meloxicam 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)

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 (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation ). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ). Hypertension NSAIDs, including meloxicam, can lead to onset of new hypertension or worsening of pre-existing 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 meloxicam, 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. Meloxicam should be used with caution in patients with fluid retention, hypertension, or heart failure. Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation NSAIDs, including meloxicam, 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 3-6 months, and in about 2-4% of 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 for 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 ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse 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 meloxicam in patients with advanced renal disease. Therefore, treatment with meloxicam is not recommended in these patients with advanced renal disease. If meloxicam therapy must be initiated, close monitoring of the patient’s renal function is advisable. Anaphylactoid Reactions As with other NSAIDS, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam. Meloxicam 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 CONTRAINDICATIONS and PRECAUTIONS, Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including meloxicam, 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. Pregnancy In late pregnancy, as with other NSAIDs, meloxicam should be avoided because it may cause premature closure of the ductus arteriosus.

ADVERSE REACTIONS Adults Osteoarthritis and Rheumatoid Arthritis The meloxicam Phase 2/3 clinical trial database includes 10,122 OA patients and 1012 RA patients treated with meloxicam, 7.5 mg/day, and 3,505 OA patients and 1351 RA patients treated with meloxicam, 15 mg/day. Meloxicam at these doses was administered to 661 patients for at least 6 months and to 312 patients for at least one year. Approximately 10,500 of these patients were treated in ten placebo and/or active-controlled osteoarthritis trials and 2363 of these patients were treated in ten placebo and/or active-controlled rheumatoid arthritis trials. Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across meloxicam trials. A 12-week multicenter, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of meloxicam with placebo and with an active control. Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of meloxicam with placebo. Table 2a depicts adverse events that occurred in ≥ 2% of the meloxicam treatment groups in a 12-week placebo and active-controlled osteoarthritis trial. Table 2a Adverse Events (%) Occurring in greater than or equal to 2% of MELOXICAM Patients in a 12-Week Osteoarthritis Placebo and Active-Controlled Trial Placebo Meloxicam 7.5 mg daily Meloxicam 15 mg daily Diclofenac 100 mg daily No. of Patients 157 154 156 153 Gastrointestinal 17.2 20.1 17.3 28.1 Abdominal Pain 2.5 1.9 2.6 1.3 Diarrhea 3.8 7.8 3.2 9.2 Dyspepsia 4.5 4.5 4.5 6.5 Flatulence 4.5 3.2 3.2 3.9 Nausea 3.2 3.9 3.8 7.2 Body as a Whole Accident Household 1.9 4.5 3.2 2.6 Edema1 2.5 1.9 4.5 3.3 Fall 0.6 2.6 0.0 1.3 Influenza-like Symptoms 5.1 4.5 5.8 2.6 Central and Peripheral Nervous System Dizziness 3.2 2.6 3.8 2.0 Headache 10.2 7.8 8.3 5.9 Respiratory Pharyingitis 1.3 0.6 3.2 1.3 Upper Respiratory Tract Infection 1.9 3.2 1.9 3.3 Skin Rash2 2.5 2.6 0.6 2.0 1 WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined Table 2b Adverse Events (%) Occurring in ≥2% of MELOXICAM Patients in two 12-Week Rheumatoid Arthritis Placebo Controlled Trials Placebo Meloxicam 7.5 mg daily Meloxicam 15 mg daily No. of Patients 469 481 477 Gastrointestinal disorders 14.1 18.9 16.8 Abdominal Pans NOS2 0.6 2.9 2.3 Diarrhea NOS2 5.1 4.8 3.4 Dyspeptic signs and symptoms1 3.8 5.8 4.0 Nausea2 2.6 3.3 3.8 General Disorders and administration site conditions Influenza like illness2 2.1 2.9 2.3 Infection and Infestations Upper respiratory tract infections-pathogen class unspecified1 4.1 7.0 6.5 Musculoskeletal and connective tissue disorders Joint related signs and symptoms1 1.9 1.5 2.3 Musculoskeletal and connective tissue signs and symptoms NEC1 3.8 1.7 2.9 Nervous system disorders Headache NOS2 6.4 6.4 5.5 Dizziness (excl vertigo)2 3.0 2.3 0.4 Skin and subcutaneous tissue disorders Rash NOS2 1.7 1.0 2.1 1 MedDRA high level term (preferred terms): dyspeptic signs and symptoms (dyspepsia, dyspepsia aggravated, eructation, gastrointestinal irritation), upper respiratory tract infections-pathogen unspecified (laryngitis NOS, pharyngitis NOS, sinusitis NOS), joint related signs and symptoms (arthralgia, arthralgia aggravated, joint crepitation, joint effusion, joint swelling), and musculoskeletal and connective tissue signs and symptoms NEC (back pain, back pain aggravated, muscle spasms, musculoskeletal pain) 2 MedDRA preferred term: diarrhea NOS, nausea, abdominal pain NOS, influenza like illness, headaches NOS, dizziness (excl vertigo), and rash NOS The adverse events that occurred with MELOXICAM in ≥ 2% of patients treated short-term (4-6 weeks) and long-term (6 months) in active controlled osteoarthritis trials are presented in Table 3. Table 3 Adverse Events (percent) Occurring in grater than or equal to 2% of MELOXICAM Patients in a 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials 4 - 6 Weeks Controlled Trials 6 Month Controlled Trials Meloxicam 7.5 mg daily Meloxicam 15 mg daily Meloxicam 7.5 mg daily Meloxicam 15 mg daily No. of Patients 8955 256 169 306 Gastrointestinal 11.8 18.0 26.6 24.2 Abdominal Pain 2.7 2.3 4.7 2.9 Constipation 0.8 1.2 1.8 2.6 Diarrhea 1.9 2.7 5.9 2.6 Dyspepsia 3.8 7.4 8.9 9.5 Flatulence 0.5 0.4 3.0 2.6 Nausea 2.4 4.7 4.7 7.2 Vomitting 0.6 0.8 1.8 2.6 Body as a Whole Edema1 0.6 2.0 2.4 1.6 Pain 0.9 2.0 3.6 5.2 Central and Peripheral Nervous System Dizziness 1.1 1.6 2.4 2.6 Headache 2.4 2.7 3.6 2.6 Hematologic Anemia 0.1 0.0 4.1 2.9 Musculoskeletal Arthralgia 0.5 0.0 5.3 1.3 Back Pain 0.5 0.4 3.0 0.7 Psychiatric Insomnia 0.4 0.0 3.6 1.6 Respiratory Coughing 0.2 0.8 2.4 1.0 Upper Respiratory Track Infection 0.2 0.0 .3 7.5 Skin Pruritis 0.4 1.2 2.4 0.0 Rash2 0.3 1.2 3.0 1.3 Urinary Micturition Frequency 0.1 0.4 2.4 1.3 Urinary Tract Infection 0.3 0.4 4.7 6.9 1 WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined Higher doses of meloxicam (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore the daily dose of meloxicam should not exceed 15 mg. The following is a list of adverse drug reactions occurring in less than 2% of patients receiving meloxicam in clinical trials involving approximately 16,200 patients. Adverse reactions reported only in worldwide post-marketing experience or the literature are shown in italics and are considered rare (less than 0.1%). Body as a Whole allergic reaction, anaphylactoid reactions including shock, face edema, fatigue, fever, hot flushes, malaise, syncope, weight decrease, weight increase Cardiovascular angina pectoris, cardiac failure, hypertension, hypotension, myocardial infarction, vasculitis Central and Peripheral Nervous System convulsions, paresthesia, tremor, vertigo Gastrointestinal colitis, dry mouth, duodenal ulcer, eructation, esophagitis, gastric ulcer, gastritis, gastroesophageal reflux, gastrointestinal hemorrhage, hematemesis, hemorrhagic duodenal ulcer,hemorrhagic gastric ulcer, intestinal perforation, melena, pancreatitis, perforated duodenal ulcer, perforated gastric ulcer, stomatitis ulcerative Heart Rate and Rhythm arrhythmia, palpitation, tachycardia Hematologic agranulocytosis, leukopenia, purpura, thrombocytopenia Liver and Biliary System ALT increased, AST increased, bilirubinemia, GGT increased, hepatitis, jaundice, liver failure Metabolic and Nutritional dehydration Psychiatric Disorders abnormal dreaming, alterations in mood (such as mood elevation) anxiety, appetite increased, confusion, depression, nervousness, somnolence Respiratory asthma, bronchospasm, dyspnea Skin and Appendages alopecia, angioedema, bullous eruption, erythema multiforme, photosensitivity reaction, pruritus, exfoliative dermatitis, Stevens-Johnson syndrome, sweating increased, toxic epidermal necrolysis, urticaria Special Senses abnormal vision, conjunctivitis, taste perversion, tinnitus Urinary System Acute urinary retention, albuminuria, BUN increased, creatinine increased, hematuria, interstitial nephritis, renal failure

<table> <caption>Table 2a Adverse Events (%) Occurring in greater than or equal to 2% of MELOXICAM Patients in a 12-Week Osteoarthritis Placebo and Active-Controlled Trial</caption> <col/> <col/> <col/> <col/> <col/> <thead> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> Placebo</td> <td styleCode=" Botrule Toprule Lrule Rrule "> Meloxicam 7.5 mg daily</td> <td styleCode=" Botrule Toprule Lrule Rrule "> Meloxicam 15 mg daily</td> <td styleCode=" Botrule Toprule Lrule Rrule "> Diclofenac 100 mg daily</td> </tr> <tr> <th styleCode=" Botrule Toprule Lrule Rrule ">No. of Patients </th> <th styleCode=" Botrule Toprule Lrule Rrule ">157 </th> <th styleCode=" Botrule Toprule Lrule Rrule ">154 </th> <th styleCode=" Botrule Toprule Lrule Rrule ">156 </th> <th styleCode=" Botrule Toprule Lrule Rrule ">153 </th> </tr> </thead> <tbody> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Gastrointestinal</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 17.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 20.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 17.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 28.1 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Abdominal Pain </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Diarrhea </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 9.2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dyspepsia </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6.5 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Flatulence </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Nausea </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Body as a Whole</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Accident Household </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Edema1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Fall </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Influenza-like Symptoms </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Central and Peripheral Nervous System</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dizziness </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.0 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Headache </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 10.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 8.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Respiratory</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Pharyingitis </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Upper Respiratory Tract Infection </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Skin</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Rash2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.0</td> </tr> </tbody> </table>

<table> <caption>Table 2b Adverse Events (%) Occurring in &#x2265;2% of MELOXICAM Patients in two 12-Week Rheumatoid Arthritis Placebo Controlled Trials</caption> <col/> <col/> <col/> <col/> <thead> <tr> <th styleCode=" Botrule Toprule Lrule Rrule "> </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Placebo </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 7.5 mg daily </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 15 mg daily </th> </tr> </thead> <tbody> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> No. of Patients</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 469</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 481</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 477</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Gastrointestinal disorders</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 14.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 18.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 16.8 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Abdominal Pans NOS2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Diarrhea NOS2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.4 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dyspeptic signs and symptoms1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.0 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Nausea2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> General Disorders and administration site conditions</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Influenza like illness2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Infection and Infestations </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Upper respiratory tract infections-pathogen class unspecified1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6.5 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Musculoskeletal and connective tissue disorders</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Joint related signs and symptoms1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Musculoskeletal and connective tissue signs and symptoms NEC1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Nervous system disorders </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Headache NOS2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.5 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dizziness (excl vertigo)2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Skin and subcutaneous tissue disorders</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Rash NOS2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.1</td> </tr> </tbody> </table>

<table> <caption>Table 3 Adverse Events (percent) Occurring in grater than or equal to 2% of MELOXICAM Patients in a 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials</caption> <col/> <col/> <col/> <col/> <col/> <thead> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4 - 6 Weeks Controlled Trials</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6 Month Controlled Trials</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <th styleCode=" Botrule Toprule Lrule Rrule "> </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 7.5 mg daily </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 15 mg daily </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 7.5 mg daily </th> <th styleCode=" Botrule Toprule Lrule Rrule ">Meloxicam 15 mg daily </th> </tr> </thead> <tbody> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> No. of Patients</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 8955</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 256</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 169</td> <td styleCode=" Botrule Toprule Lrule Rrule "> 306</td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Gastrointestinal </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 11.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 18.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 26.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 24.2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Abdominal Pain </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Constipation </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Diarrhea </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dyspepsia </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 8.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 9.5 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Flatulence </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Nausea </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Vomitting </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Body as a Whole</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Edema1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Pain </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.9 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.2 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Central and Peripheral Nervous System</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Dizziness </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Headache </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Hematologic</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Anemia </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.9 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Musculoskeletal</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Arthralgia </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 5.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Back Pain </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.5 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.7 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Psychiatric</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Insomnia </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.6 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.6 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Respiratory</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Coughing </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.8 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.0 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Upper Respiratory Track Infection </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> .3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 7.5 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Skin</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Pruritis </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.0 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Rash2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.2 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 3.0 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Urinary</td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> <td styleCode=" Botrule Toprule Lrule Rrule "> </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Micturition Frequency </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.1 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 2.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 1.3 </td> </tr> <tr> <td styleCode=" Botrule Toprule Lrule Rrule "> Urinary Tract Infection </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.3 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 0.4 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 4.7 </td> <td styleCode=" Botrule Toprule Lrule Rrule "> 6.9</td> </tr> </tbody> </table>