No data are available.

No data are available.

MOBICOX should not be used in patients with known or suspected hypersensitivity to meloxicam or any other component of MOBICOX (meloxicam) tablets. MOBICOX should not be used in patients in whom acute asthmatic attacks or symptoms of asthma, urticaria, nasal polyps, anaphylaxis, rhinitis, angioedema or other allergic manifestations are precipitated by ASA or other nonsteroidal anti-inflammatory agents since cross-sensitivity may exist. Fatal anaphylactoid reactions may occur in such individuals. Individuals with the above medical problem are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction. (see Warnings and Precautions, Anaphylactoid Reactions and Hypersensitivity Reactions).

MOBICOX is also contraindicated in:

• significant liver impairment or active liver disease;

  
  

• active or recent gastro-intestinal/gastric/duodenal/peptic ulceration/perforation, active GI bleeding,

  
  

• recent cerebrovascular bleeding or other bleeding disorders;

  
  

• severe uncontrolled heart failure;

  
  

• inflammatory bowel disease (Crohn's Disease or Ulcerative Colitis);

  
  

• severe renal impairment (creatinine clearance <30 mL/min) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored) (see Warnings and Precautions, Renal);

  
  

• known hyperkalemia;

  
  

• children and adolescents aged less than 18 years.

  
  

MOBICOX is not recommended for use with other NSAIDs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive side effects.

In case of rare hereditary conditions that may be incompatible with an excipient of the product (see Warnings and Precautions) the use of the product is contraindicated.

Caution should be exercised in prescribing MOBICOX to patients with risk factors for cardiovascular disease, cerebrovascular disease or renal disease, such as any of the following (not an exhaustive list):

• Hypertension

  
  

• Dyslipidemia/Hyperlipidemia

  
  

• Diabetes Mellitus

  
  

• Congestive Heart Failure (NYHA I)

  
  

• Coronary Artery Disease (Atherosclerosis)

  
  

• Peripheral Arterial Disease

  
  

• Smoking

  
  

• Creatinine Clearance <1 mL/s (<60 mL/min)

  
  

For relevant drug interactions that require particular attention, see Drug Interactions.

Frail or debilitated patients may tolerate side effects less well and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse event, the lowest effective dose should be used for the shortest possible duration. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

MOBICOX tablets 7.5 mg contains 47 mg lactose per maximum recommended daily dose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.

MOBICOX tablets 15 mg contains 20 mg lactose per maximum recommended daily dose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.

In rare cases, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissues diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the health care provider must be vigilant to the development of this complication.

Meloxicam was not mutagenic in the Ames test, the host- mediated assay and a mammalian gene mutation assay (V79/HPRT), nor clastogenic in a chromosome aberration assay in human lymphocytes and an in vivo micronucleus test in mouse bone marrow.

Carcinogenicity studies in rats and mice did not show any carcinogenic potential up to a dose level of 0.8 mg/kg in rats and 8 mg/kg in mice.

Risk of Cardiovascular Events: MOBICOX is a NSAID. Use of some NSAIDs is associated with an increased incidence of cardiovascular adverse events (such as myocardial infarction, stroke or thrombotic events) which can be fatal. The risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

Randomized clinical trials with MOBICOX have not been designed to detect differences in cardiovascular events in a chronic setting. Therefore, caution should be exercised when prescribing MOBICOX.

Use of NSAIDs, such as MOBICOX, can lead to new hypertension or can worsen pre-existing hypertension, either of which may increase the risk of cardiovascular events as described above. Thus blood pressure should be monitored regularly. Consideration should be given to discontinuing MOBICOX should hypertension either develop or worsen with its use.

Use of NSAIDs, such as MOBICOX, can induce fluid retention and edema, and may exacerbate congestive heart failure, through a renally-mediated mechanism.

For patients with a high risk of developing an adverse CV event, other management strategies that do not include the use of NSAIDs should be considered first. To minimize the potential risk for an adverse CV event, the lowest effective dose should be used for the shortest possible duration.

Use of NSAIDs, such as MOBICOX, can promote sodium retention in a dose-dependent manner, which can lead to fluid retention and edema, and consequences of increased blood pressure and exacerbation of congestive heart failure. Thus, caution should be exercised in prescribing MOBICOX in patients with a history of congestive heart failure, compromised cardiac function, hypertension, increased age or other conditions predisposing to fluid retention. For patients at risk, clinical monitoring is recommended.

Use of NSAIDs, such as MOBICOX, can increase the risk of hyperkalemia, especially in patients with diabetes mellitus, renal failure, increased age, or those receiving concomitant therapy with adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, cyclosporine, or some diuretics. Electrolytes should be monitored periodically.

Serious GI toxicity (sometimes fatal), such as peptic/duodenal ulceration, inflammation, perforation, obstruction and gastrointestinal bleeding, can occur at any time, with or without warning symptoms in patients treated with MOBICOX. Minor upper GI problems, such as dyspepsia, commonly occur at any time. Health care providers should remain alert for ulceration and bleeding in patients treated with MOBICOX, even in the absence of previous GI tract symptoms. 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, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Patients should be informed about the signs and/or symptoms of serious GI toxicity and instructed to discontinue using MOBICOX and seek emergency medical attention if they experience any such symptoms. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Most patients who develop a serious upper GI adverse event on NSAID therapy have no symptoms. Upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to 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 thus, increasing the likelihood of developing a serious GI event at some time during the course of therapy. Even short-term therapy has its risks.

Caution should be taken if prescribing MOBICOX to patients with a prior history of peptic/duodenal ulcer disease or gastrointestinal bleeding as these individuals have a greater than 10-fold higher risk for developing a GI bleed when taking a NSAID than patients with neither of these risk factors. Other risk factors for GI ulceration and bleeding include the following: H. pylori infection, increased age, prolonged use of NSAID therapy, excess alcohol intake, smoking, poor general health status or concomitant therapy with any of the following:

• Anticoagulants (e.g. warfarin)

  
  

• Antiplatelet agent (e.g. ASA, clopidogrel)

  
  

• Oral corticosteroids (e.g. prednisone)

  
  

• Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. citalopram, fluoxetine, paroxetine, sertraline)

  
  

Prospective, long-term studies required to compare the incidence of serious clinically significant upper gastrointestinal adverse events among patients taking meloxicam versus other NSAID products have not been performed.

For patients with a high risk of developing an adverse GI event, other management strategies that do not include the use of NSAIDs should be considered first.

There is no definitive evidence that the concomitant administration of histamine H₂ receptor antagonists and/or antacids will either prevent the occurrence of gastrointestinal adverse events or allow continuation of therapy when and if these adverse reactions appear (see Drug Interactions).

Some NSAIDs are known to cause persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Some cases have become severe on continued treatment.

Should urinary symptoms occur, treatment with MOBICOX must be stopped immediately to obtain recovery. This should be done before any urological investigations or treatments are carried out.

NSAIDs inhibiting prostaglandin biosynthesis interfere with platelet function to varying degrees; patients who may be adversely affected by such an action, such as those on anticoagulants or suffering from hemophilia or platelet disorders should be carefully observed when MOBICOX is administered.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike acetylsalicylic acid (ASA) their effect on platelet function is quantitatively less, or of shorter duration, and reversible. MOBICOX does not generally affect platelet counts, prothrombin time (PT), or partial thromboplastin time (PTT).

MOBICOX and other NSAIDs have no proven efficacy as antiplatelet agents and should not be used as a substitute for ASA or other antiplatelet agents for cardiovascular prophylaxis.

Concomitant administration of MOBICOX with low dose ASA increases the risk of GI ulceration and associated complications.

For information on interaction between low dose ASA and MOBICOX and any other interaction, see Drug Interactions, Acetylsalicylic Acid (ASA) or Other NSAIDs.

Numerous studies have shown that the concomitant use of NSAIDs and anticoagulants increases the risk of bleeding. Concurrent therapy of meloxicam with warfarin requires close monitoring of INR.

Even with therapeutic INR monitoring, increased bleeding may occur.

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anemia, and agranulocytosis) associated with the use of nonsteroidal anti-inflammatory drugs are rare, but can occur with severe consequences.

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

The incidence of treatment-related anemia is more frequent than 1%. The incidence of disturbances of blood count, including differential white cell count, leukopenia and thrombocytopenia, is between 0.1 and 1%.

As with other NSAIDs, borderline elevations of one or more liver tests (AST, ALT, alkaline phosphatase) may occur in up to 15% of patients. 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 with other NSAIDs.

Patients with signs and/or symptoms 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 MOBICOX. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), MOBICOX should be discontinued.

If there is a need to prescribe MOBICOX in the presence of impaired liver function, it must be done under strict observation.

Patients sensitive to any one of the NSAIDs may be sensitive to any of the other NSAIDs as well.

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior exposure to MOBICOX. In post-marketing experience, rare cases of anaphylactic/anaphylactoid reactions and angioedema have been reported in patients receiving MOBICOX. MOBICOX should not be given to patients with the ASA-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 ASA or other NSAIDs (See Contraindications). Emergency help should be sought in cases where anaphylactoid reaction occurs.

MOBICOX should not be given to patients with complete or partial syndrome of ASA-intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma, anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or other NSAIDs. As well, individuals with the above medical problems are at risk of a severe fatal reaction even if they have taken NSAIDs in the past without any adverse reaction (see Contraindications).

In rare cases, serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme have been associated with the use of some NSAIDs. Because the rate of these reactions is low, they have usually been noted during post-marketing surveillance in patients taking other medications also associated with the potential development of these serious skin reactions. Thus, causality is not clear. These reactions are potentially life threatening but may be reversible if the causative agent is discontinued and appropriate treatment instituted. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. MOBICOX should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Patients should be advised that if they experience a skin rash they should discontinue their NSAID and contact their physician for assessment and advice, including which additional therapies to discontinue.

MOBICOX, in common with other NSAIDs, may mask signs and symptoms of an underlying infectious disease.

Some patients may experience drowsiness, dizziness, blurred vision, vertigo, tinnitus, hearing loss, insomnia or depression with the use of MOBICOX. If patients experience these side effects, they should exercise caution in carrying out activities that require alertness.

Blurred and/or diminished vision has been reported with the use of non-steroidal anti-inflammatory drugs. If such symptoms develop MOBICOX should be discontinued and an ophthalmologic examination performed; ophthalmic examination should be carried out at periodic intervals in any patient receiving MOBICOX for an extended period of time.

See Contraindications, Coronary Artery Bypass Graft Surgery.

MOBICOX is contraindicated during pregnancy.

Inhibition of prostaglandin-synthesis may adversely affect pregnancy and/or the embryo-foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increase pre- and post implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.

During the third trimester of pregnancy all prostaglandin-synthesis inhibitors may expose the foetus to:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)

  
  

• renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

  
  

the mother and the neonate, at the end of pregnancy, to:

• possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses

  
  

• inhibition of uterine contractions resulting in delayed or prolonged labor.

  
  

MOBICOX is contraindicated for use in women who are breast-feeding because of the potential for serious adverse reactions in nursing infants. While no specific experience exists for MOBICOX, NSAIDs are known to pass into mother's milk.

See Contraindications, Warnings and Precautions.

See Warnings and Precautions, Neurologic (Central Nervous System).

Long-term administration of NSAIDs to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis, hematuria, low grade proteinuria, glomerulonephritis, renal medullary necrosis and occasionally nephrotic syndrome.

Renal insufficiency due to NSAID use is seen in patients with pre-renal conditions leading to reduction in renal blood flow or blood volume. Under these circumstances, renal prostaglandins help maintain renal perfusion and glomerular filtration rate (GFR). In these patients, administration of a NSAID may cause a reduction in prostaglandin synthesis leading to impaired renal function. Patients at greatest risk of this reaction are those with pre-existing renal insufficiency (GFR <60 mL/min or 1 mL/s), dehydrated patients, patients on salt restricted diets, those with congestive heart failure, cirrhosis, liver dysfunction, taking diuretics, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, cyclosporine and those that are elderly. Serious or life-threatening renal failure has been reported in patients with normal or impaired renal function after short-term therapy with NSAIDs. Even patients at risk who demonstrate the ability to tolerate an NSAID under stable conditions may decompensate during periods of added stress (e.g. dehydration due to gastroenteritis). Discontinuation of NSAIDs is usually followed by recovery to the pre-treatment state.

The extent to which metabolites may accumulate in patients with renal failure has not been studied with MOBICOX. As with other NSAIDs, metabolites of which are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.

Caution should be used when initiating treatment with NSAIDs in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy. Caution is also recommended in patients with pre-existing kidney disease. No dose reduction is required in patients with mild or moderate renal impairment (i.e. in patients with a creatinine clearance of greater than 15 mL/min or 0.25 mL/s) (see Warnings and Precautions, Renal).

NSAIDs can increase the risk of hyperkalemia (see Warnings and Precautions, Fluid and Electrolyte Balance).

See Contraindications.

ASA-induced asthma is an uncommon but very important indication of ASA and NSAID sensitivity. It occurs more frequently in patients with asthma who have nasal polyps.

MOBICOX is not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thromboembolic diseases. Antiplatelet therapies (e.g. ASA) should not be discontinued. There is some evidence that use of NSAIDs with ASA can markedly attenuate the cardioprotective effects of ASA. (See Drug Interactions, Drug-Drug Interaction, Acetylsalicylic Acid (ASA) or Other NSAIDs.)

MOBICOX (meloxicam) is not a substitute for corticosteroids. It does not treat corticosteroid insufficiency. Abrupt discontinutation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. The pharmacological activity of MOBICOX in reducing inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

See Warnings and Precautions, Hypersensitivity Reactions.

The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.

See Warnings and Precautions, Hypersensitivity Reactions, Serious Skin Reactions.

MOBICOX is contraindicated in pregnancy.

See Contraindications, Warnings and Precautions, Pregnancy and Lactation.

MOBICOX is contraindicated in nursing women.

See Contraindications, Warnings and Precautions, Pregnancy and Lactation.

Safety and effectiveness of MOBICOX in pediatric patients below the age of 18 years have not been evaluated.

Patients older than 65 years (hereafter referred to as older or elderly) and frail or debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs; the incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population, older patients are also at risk of a lower esophageal injury including ulceration and bleeding. For such patients, consideration should be given to a lower starting dose than the one usually recommended, with individual adjustment when necessary and under close supervision.

The following monitoring criteria and laboratory tests are recommended for patients taking MOBICOX. This is not an exhaustive list.

Laboratory Testing:

• Potassium (Renal function, Hyperkalemia)

  
  

• INR/effects of anticoagulants (co-prescription of oral anticoagulants)

  
  

• Serum transaminases and other liver function tests (liver function)

  
  

• Renal function parameters such as serum creatinine and serum urea (in case of Methotrexate, Diuretics, Cyclosporine, ACE-Inhibitor or ARB co-prescription, and in susceptible patients re: the renal effects of meloxicam, e.g. impaired renal function or dehydration)

  
  

• Lithium plasma concentrations (in case of Lithium co-prescription)

  
  

• Blood cell count, including differential white cell count (in case of Methotrexate co-prescription)

  
  

Monitoring Activities:

• Patients with GI symptoms

  
  

• Patients with oral anticoagulation (see above)

  
  

• Blood pressure (in case of Antihypertensives co-prescription, and in susceptible patients with fluid retention)

  
  

For more information, please refer to Warnings and Precautions and Drug Interactions.