FDA label 1bb99d19-6a3d-4187-b1df-b6a4db5da510

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 onselective, 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 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 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/orgastrointestinal 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 The meloxicam Phase 2/3 clinical trial database includes 10,122 OA patients treated with meloxicam 7.5 mg/day and 3505 OA 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. 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. Table 2 depicts adverse events that occurred in ≥ 2% of the meloxicam treatment groups in a 12-week placebo and active-controlled osteoarthritis trial. Table 2: Adverse Events (%) Occurring in ≥ 2% of Meloxicam Patients in a 12-Week Osteoarthritis Placebo and Active-Controlled Trial No. of Patients Placebo Meloxicam 7.5mg daily Meloxicam 15 mg daily Diclofenac 100 mg daily 157 154 156 153 Gastrointestinal Abdominal Pain 17.2 20.1 17.3 28.1 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 Edema 1 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 Pharyngitis 1.3 0.6 3.2 1.3 Upper Respiratory Tract Infection 1.9 3.2 1.9 3.3 Skin Rash 2 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 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 (%) Occurring in ≥ 2% of Meloxicam Patients in 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 Abdominal Pain 11.8 18.0 26.6 24.2 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 Vomiting 0.6 0.8 1.8 2.6 Body as a Whole Edema 1 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 Tract Infection 0.2 0.0 8.3 7.5 Skin Pruritus 0.4 1.2 2.4 0.0 Rash 2 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 <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 (<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, 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 albuminuria, BUN increased, creatinine increased, hematuria, interstitial nephritis, renal failure

<table ID="_RefID_4DB717BF-2F88-4004-96F5-DCC38927A" width="100%"> <caption>Table 2: Adverse Events (%) Occurring in &#x2265; 2% of Meloxicam Patients in a 12-Week Osteoarthritis Placebo and Active-Controlled Trial</caption> <col width="22%"/> <col width="21%"/> <col width="20%"/> <col width="18%"/> <col width="20%"/> <tbody> <tr> <td rowspan="2" styleCode="Botrule Lrule Toprule " valign="top"> <paragraph> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">No. of Patients</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Placebo</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam</content> </content> <content styleCode="emphasis"> <content styleCode="bold">7.5mg daily</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam</content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">15 mg daily</content> </content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Diclofenac </content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">100 mg daily</content> </content> </paragraph> </td> </tr> <tr> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">157</content> </content> </paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">154</content> </content> </paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">156</content> </content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">153</content> </content> </paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Gastrointestinal</content> </content> </paragraph> <paragraph> Abdominal Pain</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>17.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>20.1</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>17.3</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>28.1</paragraph> </td> </tr> <tr> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>2.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Diarrhea</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.8</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>7.8</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>9.2</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Dyspepsia</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>6.5</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Flatulence</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>3.9</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Nausea</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.9</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.8</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>7.2</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Body as a Whole</content> </content> </paragraph> <paragraph> Accident Household</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Edema¹ </paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>2.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>3.3</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Fall</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>0.6</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>0.0</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Influenza-Like Symptoms</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>5.1</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>4.5</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>5.8</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Central and Peripheral Nervous System</content> </content> </paragraph> <paragraph> Dizziness</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.8</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>2.0</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> Headache</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>10.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>7.8</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>8.3</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>5.9</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Respiratory</content> </content> </paragraph> <paragraph> Pharyngitis</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.3</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>0.6</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph>Upper Respiratory Tract Infection</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> <td align="center" styleCode="Lrule Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>3.3</paragraph> </td> </tr> <tr> <td styleCode="Botrule Lrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Skin</content> </content> </paragraph> <paragraph> Rash² </paragraph> </td> <td align="center" styleCode="Botrule Lrule " valign="top"> <paragraph>2.5</paragraph> </td> <td align="center" styleCode="Botrule Lrule " valign="top"> <paragraph>2.6</paragraph> </td> <td align="center" styleCode="Botrule Lrule " valign="top"> <paragraph>0.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>2.0</paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID_388061AE-D11D-4797-9D19-B959C6F8C" width="100%"> <caption>Table 3: Adverse Events (%) Occurring in &#x2265; 2% of Meloxicam Patients in 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials</caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tbody> <tr> <td colspan="3" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">4-6 Weeks Controlled Trials </content> </content> </paragraph> </td> <td colspan="2" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">6 Month Controlled Trials</content> </content> </paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"/> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam </content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">7.5 mg daily</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam</content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">15 mg daily</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam </content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">7.5 mg daily</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Meloxicam</content> </content> </paragraph> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">15 mg daily</content> </content> </paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">No. of Patients</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">8955</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">256</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">169</content> </content> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">306</content> </content> </paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Gastrointestinal</content> </content> </paragraph> <paragraph> Abdominal Pain</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>11.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>18.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>26.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>24.2</paragraph> </td> </tr> <tr> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.3</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.9</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Constipation</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.2</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Diarrhea</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.9</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>5.9</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Dyspepsia</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>7.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>8.9</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>9.5</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Flatulence</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Nausea</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>7.2</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Vomiting</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Body as a Whole</content> </content> </paragraph> <paragraph> Edema¹ </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Pain</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.9</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>5.2</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Central and Peripheral Nervous System</content> </content> </paragraph> <paragraph> Dizziness</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.1</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Headache</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Hematologic</content> </content> </paragraph> <paragraph> Anemia</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.1</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.1</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.9</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Musculoskeletal</content> </content> </paragraph> <paragraph> Arthralgia</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>5.3</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Back Pain</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.7</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Psychiatric</content> </content> </paragraph> <paragraph> Insomnia</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.6</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.6</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Respiratory</content> </content> </paragraph> <paragraph> Coughing</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.2</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.8</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.0</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Upper Respiratory</paragraph> <paragraph> Tract Infection</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.2</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>8.3</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>7.5</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold"> Skin</content> </content> </paragraph> <paragraph> Pruritus</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.2</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.0</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Rash² </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.3</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.2</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>3.0</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Urinary</content> </content> </paragraph> <paragraph> Micturition</paragraph> <paragraph> Frequency</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.1</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>2.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> Urinary Tract </paragraph> <paragraph> Infection</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.3</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>0.4</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.7</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>6.9</paragraph> </td> </tr> </tbody> </table>

<table width="100%"> <col width="36%"/> <col width="64%"/> <tbody> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Body as a Whole</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>allergic reaction, <content styleCode="italics">anaphylactoid reactions including shock, </content>face edema, fatigue, fever, hot flushes, malaise, syncope, weight decrease, weight increase</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Cardiovascular</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>angina pectoris, cardiac failure, hypertension, hypotension, myocardial infarction, vasculitis</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Central and Peripheral Nervous System</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>convulsions, paresthesia, tremor, vertigo</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Gastrointestinal</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>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</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Heart Rate and Rhythm</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>arrhythmia, palpitation, tachycardia</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Hematologic</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="italics">agranulocytosis, </content>leukopenia, purpura, thrombocytopenia</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Liver and Biliary System</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>ALT increased, AST increased, bilirubinemia, GGT increased, hepatitis,<content styleCode="italics"> jaundice, liver failure</content> </paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Metabolic and Nutritional</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>dehydration</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Psychiatric Disorders</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>abnormal dreaming, anxiety, appetite increased, confusion, depression, nervousness, somnolence</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Respiratory</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>asthma, bronchospasm, dyspnea</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Skin and Appendages</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>alopecia, angioedema, bullous eruption, <content styleCode="italics">erythema multiforme, </content>photosensitivity reaction, pruritus, <content styleCode="italics">exfoliative dermatitis</content>, <content styleCode="italics">Stevens-Johnson syndrome, </content>sweating increased, <content styleCode="italics">toxic epidermal necrolysis, </content>urticaria</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Special Senses</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>abnormal vision, conjunctivitis, taste perversion, tinnitus</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph> <content styleCode="emphasis"> <content styleCode="bold">Urinary System</content> </content> </paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>albuminuria, BUN increased, creatinine increased, hematuria, <content styleCode="italics">interstitial nephritis, </content>renal failure</paragraph> </td> </tr> </tbody> </table>