Mobic®
(meloxicam)
Tablets 7.5 mg and 15 mg
and
Mobic®
(meloxicam)
Oral Suspension 7.5 mg/5 mL

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).
  
  
• MOBIC tablets/oral suspension 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).

Meloxicam, an oxicam derivative, is a member of the enolic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each pastel yellow MOBIC tablet contains 7.5 mg or 15 mg meloxicam for oral administration. Each bottle of MOBIC oral suspension contains 7.5 mg meloxicam per 5 mL. Meloxicam is chemically designated as 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide. The molecular weight is 351.4. Its empirical formula is C₁₄H₁₃N₃O₄S₂ and it has the following structural formula.

Meloxicam is a pastel yellow solid, practically insoluble in water, with higher solubility observed in strong acids and bases. It is very slightly soluble in methanol. Meloxicam has an apparent partition coefficient (log P)_app = 0.1 in n-octanol/buffer pH 7.4. Meloxicam has pKa values of 1.1 and 4.2.

MOBIC is available as a tablet for oral administration containing 7.5 mg or 15 mg meloxicam, and as an oral suspension containing 7.5 mg meloxicam per 5 mL.

The inactive ingredients in Mobic^® (meloxicam) tablets include colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium citrate dihydrate.

The inactive ingredients in Mobic^® (meloxicam) oral suspension include colloidal silicon dioxide, hydroxyethylcellulose, sorbitol, glycerol, xylitol, monobasic sodium phosphate (dihydrate), saccharin sodium, sodium benzoate, citric acid (monohydrate), raspberry flavor, and purified water.

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of meloxicam, like that of other NSAIDs, may be related to prostaglandin synthetase (cyclo-oxygenase) inhibition.

The use of MOBIC for the treatment of the signs and symptoms of osteoarthritis of the knee and hip was evaluated in a 12-week double-blind controlled trial. MOBIC (3.75 mg, 7.5 mg and 15 mg daily) was compared to placebo. The four primary endpoints were investigator’s global assessment, patient global assessment, patient pain assessment, and total WOMAC score (a self-administered questionnaire addressing pain, function and stiffness). Patients on MOBIC 7.5 mg daily and MOBIC 15 mg daily showed significant improvement in each of these endpoints compared with placebo.

The use of MOBIC for the management of signs and symptoms of osteoarthritis was evaluated in six double-blind, active-controlled trials outside the U.S. ranging from 4 weeks to 6 months duration. In these trials, the efficacy of MOBIC, in doses of 7.5 mg/day and 15 mg/day, was comparable to piroxicam 20 mg/day and diclofenac SR 100 mg/day and consistent with the efficacy seen in the U.S. trial.

The use of MOBIC for the treatment of the signs and symptoms of rheumatoid arthritis was evaluated in a 12-week double-blind, controlled multinational trial. MOBIC (7.5 mg, 15 mg and 22.5 mg daily) was compared to placebo. The primary endpoint in this study was the ACR20 response rate, a composite measure of clinical, laboratory and functional measures of RA response. Patients receiving MOBIC 7.5 mg and 15 mg daily showed significant improvement in the primary endpoint compared with placebo. No incremental benefit was observed with the 22.5 mg dose compared to the 15 mg dose.

Higher doses of MOBIC (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore the daily dose of MOBIC should not exceed 15 mg.

The use of MOBIC for the treatment of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients 2 years of age and older was evaluated in two 12-week, double-blind, parallel-arm, active-controlled trials. Both studies included three arms: naproxen and two doses of meloxicam. In both studies, meloxicam dosing began at 0.125 mg/kg/day (7.5 mg maximum) or 0.25 mg/kg/day (15 mg maximum), and naproxen dosing began at 10 mg/kg/day. One study used these doses throughout the 12-week dosing period, while the other incorporated a titration after 4 weeks to doses of 0.25 mg/kg/day and 0.375 mg/kg/day (22.5 mg maximum) of meloxicam and 15 mg/kg/day of naproxen.

The efficacy analysis used the ACR Pediatric 30 responder definition, a composite of parent and investigator assessments, counts of swollen active joints and joints with limited range of motion, and erythrocyte sedimentation rate. The proportion of responders were similar in all three groups in both studies, and no difference was observed between the meloxicam dose groups.

Carefully consider the potential benefits and risks of Mobic^® (meloxicam) tablets/oral suspension and other treatment options before deciding to use MOBIC tablets/oral suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

MOBIC tablets/oral suspension is indicated for relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis.

MOBIC tablets/oral suspension is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients 2 years of age and older.

MOBIC tablets/oral suspension is contraindicated in patients with known hypersensitivity to meloxicam.

MOBIC tablets/oral suspension 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, Pre-existing Asthma).

MOBIC tablets/oral suspension is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Long-term administration of NSAIDs, including Mobic® (meloxicam) tablets/oral suspension, can result in renal papillary necrosis, renal insufficiency, acute renal failure, 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, ACE inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

No information is available from controlled clinical studies regarding the use of MOBIC tablets/oral suspension in patients with advanced renal disease. Therefore, treatment with MOBIC tablets/oral suspension is not recommended in these patients with advanced renal disease. If MOBIC tablets/oral suspension therapy must be initiated, close monitoring of the patient's renal function is advisable.

As with other NSAIDS, anaphylactoid reactions have occurred in patients without known prior exposure to MOBIC tablets/oral suspension. MOBIC tablets/oral suspension 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.

NSAIDs, including MOBIC tablets/oral suspension, 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.

In late pregnancy, as with other NSAIDs, MOBIC tablets/oral suspension should be avoided because it may cause premature closure of the ductus arteriosus.

Mobic^® (meloxicam) tablets/oral suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of MOBIC tablets/oral suspension in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including MOBIC tablets/oral suspension. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with MOBIC tablets/oral suspension. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), MOBIC tablets/oral suspension should be discontinued.

Caution should be used when initiating treatment with MOBIC tablets/oral suspension in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with MOBIC tablets/oral suspension. Caution is also recommended in patients with pre-existing kidney disease (see WARNINGS, Renal Effects and Advanced Renal Disease).

The extent to which metabolites may accumulate in patients with renal failure has not been studied with MOBIC tablets/oral suspension. Because some MOBIC tablets/oral suspension metabolites are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.

Anemia is sometimes seen in patients receiving NSAIDs, including MOBIC tablets/oral suspension. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including MOBIC tablets/oral suspension, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

Drugs which inhibit the biosynthesis of prostaglandins may interfere to some extent with platelet function and vascular responses to bleeding.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Mobic^® (meloxicam) tablets/oral suspension who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, MOBIC tablets/oral suspension should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

• MOBIC tablets/oral suspension, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
  
  
• MOBIC tablets/oral suspension, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation).
  
  
• MOBIC tablets/oral suspension, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and bulers, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
  
  
• Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
  
  
• Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
  
  
• Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
  
  
• In late pregnancy, as with other NSAIDs, Mobic^® (meloxicam) tablets/oral suspension should be avoided because it may cause premature closure of the ductus arteriosus.

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, MOBIC tablets/oral suspension should be discontinued.

No carcinogenic effect of meloxicam was observed in rats given oral doses up to 0.8 mg/kg/day (approximately 0.4-fold the human dose at 15 mg/day for a 50 kg adult based on body surface area conversion) for 104 weeks or in mice given oral doses up to 8.0 mg/kg/day (approximately 2.2-fold the human dose, as noted above) for 99 weeks.

Meloxicam was not mutagenic in an Ames assay, or clastogenic in a chromosome aberration assay with human lymphocytes and an in vivo micronucleus test in mouse bone marrow.

Meloxicam did not impair male and female fertility in rats at oral doses up to 9 and 5 mg/kg/day, respectively (4.9-fold and 2.5-fold the human dose, as noted above). However, an increased incidence of embryolethality at oral doses ≥ 1 mg/kg/day (0.5-fold the human dose, as noted above) was observed in rats when dams were given meloxicam 2 weeks prior to mating and during early embryonic development.

Studies in rats with meloxicam, as with other drugs known to inhibit prostaglandin synthesis, showed an increased incidence of stillbirths, prolonged delivery, and delayed parturition at oral dosages ≥ 1 mg/kg/day (approximately 0.5-fold the human dose at 15 mg/day for a 50 kg adult based on body surface area conversion), and decreased pup survival at an oral dose of 4 mg/kg/day (approximately 2.1-fold the human dose, as noted above) throughout organogenesis. Similar findings were observed in rats receiving oral dosages ≥ 0.125 mg/kg/day (approximately 0.07-fold the human dose, as noted above) during late gestation and the lactation period.

The effects of MOBIC tablets/oral suspension on labor and delivery in pregnant women are unknown.

It is not known whether this drug is excreted in human milk however, meloxicam was excreted in the milk of lactating rats at concentrations higher than those in plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MOBIC tablets/oral suspension, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The safety and effectiveness of meloxicam in pediatric JRA patients from 2 to 17 years of age has been evaluated in three clinical trials (see CLINICAL TRIALS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections).

As with any NSAID, caution should be exercised in treating the elderly (65 years and older).

There is limited experience with meloxicam overdose. Four cases have taken 6 to 11 times the highest recommended dose; all recovered. Cholestyramine is known to accelerate the clearance of meloxicam.

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.

Patients should be managed with symptomatic and supportive care following an NSAID overdose. In cases of acute overdose, gastric lavage followed by activated charcoal is recommended. Gastric lavage performed more than one hour after overdose has little benefit in the treatment of overdose. Administration of activated charcoal is recommended for patients who present 1-2 hours after overdose. For substantial overdose or severely symptomatic patients, activated charcoal may be administered repeatedly. Accelerated removal of meloxicam by 4 gm oral doses of cholestyramine given three times a day was demonstrated in a clinical trial. Administration of cholestyramine may be useful following an overdose. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

Carefully consider the potential benefits and risks of Mobic^® (meloxicam) tablets/oral suspension and other treatment options before deciding to use MOBIC tablets/oral suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with MOBIC tablets/oral suspension, the dose should be adjusted to suit an individual patient's needs.

For the relief of the signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of MOBIC is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily. For the relief of the signs and symptoms of rheumatoid arthritis, the recommended starting and maintenance oral dose of MOBIC is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily.

MOBIC oral suspension 7.5 mg/5 mL or 15 mg/10 mL may be substituted for MOBIC tablets 7.5 mg or 15 mg, respectively.

The maximum recommended daily oral dose of MOBIC is 15 mg regardless of formulation.

MOBIC oral suspension is available in the strength of 7.5 mg/5 mL. To improve dosing accuracy in smaller weight children, the use of the MOBIC oral suspension is recommended. For the treatment of juvenile rheumatoid arthritis, the recommended oral dose of MOBIC is 0.125 mg/kg once daily up to a maximum of 7.5mg. There was no additional benefit demonstrated by increasing the dose above 0.125 mg/kg once daily in these clinical trials.

Juvenile Rheumatoid Arthritis dosing using the oral suspension should be individualized based on the weight of the child:

Shake the oral suspension gently before using.

Mobic^® (meloxicam) tablets/oral suspension may be taken without regard to timing of meals.

MOBIC is available as a pastel yellow, round, biconvex, uncoated tablet containing meloxicam 7.5 mg or as a pastel yellow, oblong, biconvex, uncoated tablet containing meloxicam 15 mg. The 7.5 mg tablet is impressed with the Boehringer Ingelheim logo on one side, and on the other side, the letter “M”. The 15 mg tablet is impressed with the tablet code “15” on one side and the letter “M” on the other. MOBIC is also available as a yellowish green tinged viscous oral suspension containing 7.5 mg meloxicam in 5 mL.

MOBIC tablets 7.5 mg is available as follows:
    NDC 0597-0029-01; Bottles of 100

MOBIC tablets 15 mg is available as follows:
    NDC 0597-0030-01; Bottles of 100

MOBIC oral suspension 7.5mg/5mL is available as follows:
    NDC 0597-0034-01; Bottles of 100 mL