Meloxicam

Meloxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) that are used to treat pain and/or inflammation. Other members of this class include ibuprofen (Motrin), indomethacin (Indocin), nabumetone (Relafen) and several others. Prostaglandins are chemicals that contribute to inflammation especially within joints, and it is the inflammation that leads to the common symptoms of pain, tenderness, and swelling associated with arthritis. Meloxicam blocks the enzymes that make prostaglandins (cyclooxygenase 1 and 2) and reduces the levels of prostaglandins. As a result, inflammation and its accompanying symptoms are reduced. Meloxicam was approved for use in April 2000.

1-10%

Indigestion (3.8-9.5%)

Upper respiratory infection (≤8.3%)

Headache (2.4-8.3%)

Diarrhea (1.9-7.8%)

Nausea (2.4-7.2%)

Abdominal pain (1.9-4.7%)

Edema (0.6-4.5%)

Anemia (≤4.1%)

Dizziness (1.1-3.8%)

Constipation (0.8-2.6%)

Angina (<2%)

Congestive heart failure (<2%)

Decreased platelet aggregation, purpuric disorder (<2%)

Gastrointestinal (GI) hemorrhage (<2%)

GI perforation, GI ulcer (<2%)

Hepatitis (<2%)

Hypertension (<2%)

Inflammatory disorder of digestive tract (<2%)

Myocardial infarction (<2%)

Vomiting (<3%)

<1%

Anaphylactoid reaction

Angioedema

Fever

Asthma, bronchospasm

Cerebrovascular accident

Erythema multiforme, erythroderma

Immune hypersensitivity reaction

Interstitial nephritis, renal failure

Jaundice, liver failure

Stevens-Johnson syndrome

Tinnitus, hearing loss

Toxic epidermal necrolysis

Mechanism Of Action

Meloxicam has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of MOBIC, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Meloxicam is a potent inhibitor of prostaglandin synthesis in vitro. Meloxicam concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because meloxicam is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Pharmacokinetics

The absolute bioavailability of meloxicam capsules was 89% following a single oral dose of 30 mg compared with 30 mg IV bolus injection. Following single intravenous doses, dose-proportional pharmacokinetics were shown in the range of 5 mg to 60 mg. After multiple oral doses the pharmacokinetics of meloxicam capsules were dose-proportional over the range of 7.5 mg to 15 mg. Mean Cmax was achieved within four to five hours after a 7.5 mg meloxicam tablet was taken under fasted conditions, indicating a prolonged drug absorption. With multiple dosing, steady-state concentrations were reached by Day 5. A second meloxicam concentration peak occurs around 12 to 14 hours post-dose suggesting biliary recycling.

Meloxicam oral suspension doses of 7.5 mg/5 mL and 15 mg/10 mL have been found to be bioequivalent to meloxicam 7.5 mg and 15 mg capsules, respectively. Meloxicam capsules have been shown to be bioequivalent to MOBIC tablets.

Table 4 : Single Dos e and Steady-State Pharmacokinetic Parameters for Oral 7.5 mg and 15 mg Meloxicam (Mean and % CV)1

Administration of meloxicam capsules following a high fat breakfast (75 g of fat) resulted in mean peak drug levels (i.e., Cmax) being increased by approximately 22% while the extent of absorption (AUC) was unchanged. The time to maximum concentration (Tmax) was achieved between 5 and 6 hours. In comparison, neither the AUC nor the Cmax values for meloxicam suspension were affected following a similar high fat meal, while mean Tmax values were increased to approximately 7 hours. No pharmacokinetic interaction was detected with concomitant administration of antacids. Based on these results, MOBIC can be administered without regard to timing of meals or concomitant administration of antacids.

The mean volume of distribution (Vss) of meloxicam is approximately 10 L. Meloxicam is ~99.4% bound to human plasma proteins (primarily albumin) within the therapeutic dose range. The fraction of protein binding is independent of drug concentration, over the clinically relevant concentration range, but decreases to ~99% in patients with renal disease. Meloxicam penetration into human red blood cells, after oral dosing, is less than 10%. Following a radiolabeled dose, over 90% of the radioactivity detected in the plasma was present as unchanged meloxicam.

Meloxicam concentrations in synovial fluid, after a single oral dose, range from 40% to 50% of those in plasma. The free fraction in synovial fluid is 2.5 times higher than in plasma, due to the lower albumin content in synovial fluid as compared to plasma. The significance of this penetration is unknown.

Metabolism

Meloxicam is extensively metabolized in the liver. Meloxicam metabolites include 5'-carboxy meloxicam (60% of dose), from P-450 mediated metabolism formed by oxidation of an intermediate metabolite 5'hydroxymethyl meloxicam which is also excreted to a lesser extent (9% of dose). In vitro studies indicate that CYP2C9 (cytochrome P450 metabolizing enzyme) plays an important role in this metabolic pathway with a minor contribution of the CYP3A4 isozyme. Patients' peroxidase activity is probably responsible for the other two metabolites which account for 16% and 4% of the administered dose, respectively. All the four metabolites are not known to have any in vivo pharmacological activity.

Excretion

Meloxicam excretion is predominantly in the form of metabolites, and occurs to equal extents in the urine and feces. Only traces of the unchanged parent compound are excreted in the urine (0.2%) and feces (1.6%). The extent of the urinary excretion was confirmed for unlabeled multiple 7.5 mg doses: 0.5%, 6%, and 13% of the dose were found in urine in the form of meloxicam, and the 5'hydroxymethyl and 5'carboxy metabolites, respectively. There is significant biliary and/or enteral secretion of the drug. This was demonstrated when oral administration of cholestyramine following a single IV dose of meloxicam decreased the AUC of meloxicam by 50%.

The mean elimination half-life (t1/2) ranges from 15 hours to 20 hours. The elimination half-life is constant across dose levels indicating linear metabolism within the therapeutic dose range. Plasma clearance ranges from 7 to 9 mL/min.

Specific Populations

After single (0.25 mg/kg) dose administration and after achieving steady state (0.375 mg/kg/day), there was a general trend of approximately 30% lower exposure in younger patients (2 to 6 years old) as compared to the older patients (7 to 16 years old). The older patients had meloxicam exposures similar (single dose) or slightly reduced (steady state) to those in the adult patients, when using AUC values normalized to a dose of 0.25 mg/kg [see DOSAGE AND ADMINISTRATION]. The meloxicam mean (SD) elimination half-life was 15.2 (10.1) and 13.0 hours (3.0) for the 2 to 6 year old patients, and 7 to 16 year old patients, respectively.

In a covariate analysis, utilizing population pharmacokinetics body-weight, but not age, was the single predictive covariate for differences in the meloxicam apparent oral plasma clearance. The body-weight normalized apparent oral clearance values were adequate predictors of meloxicam exposure in pediatric patients.

The pharmacokinetics of MOBIC in pediatric patients under 2 years of age have not been investigated.

Elderly males ( ≥ 65 years of age) exhibited meloxicam plasma concentrations and steady-state pharmacokinetics similar to young males. Elderly females ( ≥ 65 years of age) had a 47% higher AUCss and 32% higher Cmax,ss as compared to younger females ( ≤ 55 years of age) after body weight normalization. Despite the increased total concentrations in the elderly females, the adverse event profile was comparable for both elderly patient populations. A smaller free fraction was found in elderly female patients in comparison to elderly male patients.

Young females exhibited slightly lower plasma concentrations relative to young males. After single doses of 7.5 mg MOBIC, the mean elimination half-life was 19.5 hours for the female group as compared to 23.4 hours for the male group. At steady state, the data were similar (17.9 hours vs 21.4 hours). This pharmacokinetic difference due to gender is likely to be of little clinical importance. There was linearity of pharmacokinetics and no appreciable difference in the Cmax or Tmax across genders.

Following a single 15 mg dose of meloxicam there was no marked difference in plasma concentrations in patients with mild (Child-Pugh Class I) or moderate (Child-Pugh Class II) hepatic impairment compared to healthy volunteers. Protein binding of meloxicam was not affected by hepatic impairment. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment (Child-Pugh Class III) have not been adequately studied [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].

Meloxicam pharmacokinetics have been investigated in subjects with mild and moderate renal impairment. Total drug plasma concentrations of meloxicam decreased and total clearance of meloxicam increased with the degree of renal impairment while free AUC values were similar in all groups. The higher meloxicam clearance in subjects with renal impairment may be due to increased fraction of unbound meloxicam which is available for hepatic metabolism and subsequent excretion. No dosage adjustment is necessary in patients with mild to moderate renal impairment. Patients with severe renal impairment have not been adequately studied. The use of MOBIC in subjects with severe renal impairment is not recommended [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and Use in Specific Populations].

Following a single dose of meloxicam, the free C plasma concentrations were higher in patients with renal failure on chronic hemodialysis (1% free fraction) in comparison to healthy volunteers (0.3% free fraction). Hemodialysis did not lower the total drug concentration in plasma; therefore, additional doses are not necessary after hemodialysis. Meloxicam is not dialyzable [see DOSAGE AND ADMINISTRATION and Use in Specific Populations].

Drug Interaction Studies

Aspirin: When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered. When MOBIC is administered with aspirin (1000 mg three times daily) to healthy volunteers, it tended to increase the AUC (10%) and C (24%) of meloxicam. The clinical significance of this interaction is not known. See Table 3 for clinically significant drug interactions of NSAIDs with aspirin [see DRUG INTERACTIONS].

Cholestyramine: Pretreatment for four days with cholestyramine significantly increased the clearance of meloxicam by 50%. This resulted in a decrease in t , from 19.2 hours to 12.5 hours, and a 35% reduction in AUC. This suggests the existence of a recirculation pathway for meloxicam in the gastrointestinal tract. The clinical relevance of this interaction has not been established.

Cimetidine: Concomitant administration of 200 mg cimetidine four times daily did not alter the singledose pharmacokinetics of 30 mg meloxicam.

Digoxin: Meloxicam 15 mg once daily for 7 days did not alter the plasma concentration profile of digoxin after β-acetyldigoxin administration for 7 days at clinical doses. In vitro testing found no protein binding drug interaction between digoxin and meloxicam.

Lithium: In a study conducted in healthy subjects, mean pre-dose lithium concentration and AUC were increased by 21% in subjects receiving lithium doses ranging from 804 to 1072 mg twice daily with meloxicam 15 mg QD every day as compared to subjects receiving lithium alone [see DRUG INTERACTIONS].

Methotrexate: A study in 13 rheumatoid arthritis (RA) patients evaluated the effects of multiple doses of meloxicam on the pharmacokinetics of methotrexate taken once weekly. Meloxicam did not have a significant effect on the pharmacokinetics of single doses of methotrexate. In vitro, methotrexate did not displace meloxicam from its human serum binding sites [see DRUG INTERACTIONS].

Warfarin: The effect of meloxicam on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of warfarin that produced an INR (International Normalized Ratio) between 1.2 and 1.8. In these subjects, meloxicam did not alter warfarin pharmacokinetics and the average anticoagulant effect of warfarin as determined by prothrombin time. However, one subject showed an increase in INR from 1.5 to 2.1. Caution should be used when administering MOBIC with warfarin since patients on warfarin may experience changes in INR and an increased risk of bleeding complications when a new medication is introduced [see DRUG INTERACTIONS].

Clinical Studies

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.

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 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.

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID). Meloxicam works by reducing hormones that cause inflammation and pain in the body.

Meloxicam is used to treat pain or inflammation caused by osteoarthritis or rheumatoid arthritis in adults and children who are at least 2 years old.

Meloxicam may also be used for purposes not listed in this medication guide.

Do not use meloxicam just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

This medicine may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking meloxicam, especially in older adults.

You should not use this medication if you are allergic to meloxicam, or if you have a history of allergic reaction to aspirin or other NSAIDs.

Meloxicam may cause a delay in ovulation (the release of an egg from an ovary). You should not take meloxicam if you are undergoing fertility treatment, or are otherwise trying to get pregnant.

To make sure you can safely take meloxicam, tell your doctor if you have any of these other conditions:

• a history of heart attack, stroke, or blood clot;
• heart disease, congestive heart failure, high blood pressure;
• a history of stomach ulcers or bleeding;
• liver or kidney disease,
• a seizure disorder such as epilepsy;
• asthma;
• polyps in your nose; or
• if you smoke.

FDA pregnancy category D. Taking meloxicam during the last 3 months of pregnancy may harm the unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using meloxicam.

Meloxicam can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medicine to a child younger than 2 years old without the advice of a doctor.

Consider potential benefits and risks of meloxicam therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1

Osteoarthritis

Symptomatic treatment of osteoarthritis.1 Effect comparable to that of other NSAIAs (piroxicam, diclofenac).1 11 12 13 14 15

Rheumatoid Arthritis in Adults

Symptomatic treatment of rheumatoid arthritis in adults.1 18 19

Juvenile Arthritis

Symptomatic management of pauciarticular or polyarticular course juvenile rheumatoid arthritis in children ≥2 years of age.1 23 Effect comparable to that of naproxen.1 23

Cardiovascular Risk Reduction

Not a substitute for aspirin in the prevention of adverse cardiovascular events (MI).1

Contraindications

• Known hypersensitivity to meloxicam or any ingredient in the formulation.1

• History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1

• In the setting of CABG surgery.508

Warnings/Precautions

Warnings

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.500 502 508

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.26 27 28 30 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.1 500 508

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 502 508 (See Specific Drugs under Interactions.)

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1

Lower incidence of adverse GI effects compared with other prototypical NSAIAs (e.g., diclofenac, naproxen, piroxicam) in some studies.16 17

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.1 508 (See Specific Drugs under Interactions.)

Fluid retention and edema reported.1 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1

Potential for overt renal decompensation.1 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 20 29 (See Renal Impairment under Cautions.)

Correct dehydration before initiating meloxicam therapy.1

Sensitivity Reactions

Anaphylactoid reactions reported.1

Immediate medical intervention and discontinuance for anaphylaxis.1

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1

General Precautions

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1

Elevations of serum ALT or AST reported.1

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1

Anemia reported rarely.1 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.1

Notable effects on platelets or bleeding times not observed.3 8 9

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1

May mask certain signs of infection.1

Obtain CBC and chemistry profile periodically during long-term use.1

Specific Populations

Category C.1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1

Distributed into milk in rats; not known whether distributed into milk in humans.1 Discontinue nursing or the drug.1

Safety and efficacy not established in children <2 years of age.1

Safety and efficacy in pediatric patients 2–17 years of age with juvenile rheumatoid arthritis supported by evidence from controlled studies.1 23

Abdominal pain, vomiting, diarrhea, headache, and pyrexia reported more frequently in children than adults.1

Caution advised.1 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1

Not studied in patients with severe hepatic impairment (Child-Pugh class III).1

Use with caution in renal disease.1 Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1

Common Adverse Effects

Abdominal pain, diarrhea, dizziness, dyspepsia, edema, flatulence, headache, nausea, rash, upper respiratory tract infection, influenza-like illness, musculoskeletal and connective tissue signs and symptoms (back pain, muscle spasms, musculoskeletal pain).1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In the U.S.

• Mobic
• Vivlodex

Available Dosage Forms:

• Capsule
• Tablet
• Suspension

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Oxicam

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For meloxicam, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to meloxicam or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of meloxicam oral liquid or tablets in children with juvenile rheumatoid arthritis 2 years of age and older.

Appropriate studies have not been performed on the relationship of age to the effects of meloxicam capsules in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of meloxicam in the elderly. However, elderly patients are more likely to have serious stomach, heart, or kidney problems, which may require caution and an adjustment in the dose for patients receiving meloxicam.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking meloxicam, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using meloxicam with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac

Using meloxicam with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Amiloride
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Balsalazide
• Bemiparin
• Bendroflumethiazide
• Benzthiazide
• Betamethasone
• Betrixaban
• Bismuth Subsalicylate
• Bivalirudin
• Bromfenac
• Budesonide
• Bufexamac
• Bumetanide
• Cangrelor
• Celecoxib
• Ceritinib
• Certoparin
• Chlorothiazide
• Chlorthalidone
• Choline Magnesium Trisalicylate
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopamide
• Clopidogrel
• Cortisone
• Cyclopenthiazide
• Cyclosporine
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Deflazacort
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexibuprofen
• Dexketoprofen
• Diazoxide
• Dibenzepin
• Diclofenac
• Diflunisal
• Digoxin
• Dipyridamole
• Dipyrone
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Enoxaparin
• Eplerenone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Feverfew
• Floctafenine
• Flufenamic Acid
• Fluocortolone
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Furosemide
• Ginkgo
• Gossypol
• Heparin
• Hydrochlorothiazide
• Hydrocortisone
• Hydroflumethiazide
• Ibuprofen
• Iloprost
• Imipramine
• Indapamide
• Indomethacin
• Ketoprofen
• Lepirudin
• Levomilnacipran
• Lithium
• Lofepramine
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Magnesium Salicylate
• Meadowsweet
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Mesalamine
• Methotrexate
• Methyclothiazide
• Methylprednisolone
• Metolazone
• Milnacipran
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Olsalazine
• Opipramol
• Oxaprozin
• Oxyphenbutazone
• Paramethasone
• Parecoxib
• Parnaparin
• Paroxetine
• Pemetrexed
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Phenyl Salicylate
• Piketoprofen
• Piroxicam
• Polythiazide
• Pralatrexate
• Prasugrel
• Prednisolone
• Prednisone
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Reboxetine
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylamide
• Salicylic Acid
• Salsalate
• Sertraline
• Sibutramine
• Sodium Polystyrene Sulfonate
• Sodium Salicylate
• Spironolactone
• Sulfasalazine
• Sulindac
• Tacrolimus
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Treprostinil
• Triamterene
• Trichlormethiazide
• Trimipramine
• Trolamine Salicylate
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Xipamide

Using meloxicam with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Alacepril
• Atenolol
• Azilsartan
• Azilsartan Medoxomil
• Benazepril
• Betaxolol
• Bisoprolol
• Candesartan
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cholestyramine
• Cilazapril
• Delapril
• Enalapril
• Enalaprilat
• Eprosartan
• Esmolol
• Fosinopril
• Imidapril
• Irbesartan
• Itraconazole
• Labetalol
• Levobunolol
• Lisinopril
• Losartan
• Metipranolol
• Metoprolol
• Moexipril
• Nadolol
• Nebivolol
• Olmesartan
• Oxprenolol
• Penbutolol
• Pentopril
• Perindopril
• Pindolol
• Practolol
• Propranolol
• Quinapril
• Ramipril
• Sotalol
• Spirapril
• Telmisartan
• Temocapril
• Timolol
• Trandolapril
• Valsartan
• Voriconazole
• Zofenopril

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of meloxicam. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Asthma or
• Bleeding problems or
• Congestive heart failure or
• Dehydration or
• Edema (fluid retention or body swelling) or
• Heart attack, history of or
• Heart or blood vessel disease or
• Hyperkalemia (high blood potassium) or
• Hypertension (high blood pressure) or
• Kidney disease or
• Liver disease or
• Stomach ulcers or bleeding, history of or
• Stroke, history of—Use with caution. May make these conditions worse.

• Aspirin-sensitive asthma or
• Aspirin sensitivity, history of—Should not be used in patients with these conditions.

• Heart surgery (eg, coronary artery bypass graft [CABG])—Meloxicam should not be used for pain right before or after the surgery.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

There was no increase in tumor incidence in long-term carcinogenicity studies in rats (104 weeks) and mice (99 weeks) administered Meloxicam at oral doses up to 0.8 mg/kg/day in rats and up to 8.0 mg/kg/day in mice (up to 0.5-and 2.6-times, respectively, the maximum recommended human dose [MRHD] of 15 mg/day Meloxicam based on body surface area [BSA] comparison).

Mutagenesis

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.

Impairment of Fertility

Meloxicam did not impair male and female fertility in rats at oral doses up to 9 mg/kg/day in males and 5 mg/kg/day in females (up to 5.8- and 3.2-times greater, respectively, than the MRHD based on BSA comparison).

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed.

Inform patients, families or their caregivers of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately [see Warnings and Precautions (5.1)].

Gastrointestinal Bleeding, Ulceration, and Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their healthcare provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for the signs and symptoms of GI bleeding [see Warnings and Precautions (5.2)].

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, instruct patients to stop Meloxicam and seek immediate medical therapy [see Warnings and Precautions (5.3)].

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions (5.5)].

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see Contraindications (4) and Warnings and Precautions (5.7)].

Serious Skin Reactions

Advise patients to stop Meloxicam immediately if they develop any type of rash and to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.9)].

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including Meloxicam, may be associated with a reversible delay in ovulation [see Use in Specific Populations (8.3)].

Fetal Toxicity

Inform pregnant women to avoid use of Meloxicam and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus [see Warnings and Precautions (5.10) and Use in Specific Populations (8.1)].

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of Meloxicam with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.2) and Drug Interactions (7)]. Alert patients that NSAIDs may be present in "over the counter" medications for treatment of colds, fever, or insomnia.

Use of NSAIDs and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with Meloxicam until they talk to their healthcare provider [see Drug Interactions (7)].

*Kayexalate is a registered trademark of Sanofi-Aventis

Please address medical inquiries to, (MedicalAffairs@zydususa.com) Tel.: 1-877-993-8779.

Manufactured by:

Cadila Healthcare Ltd.

India.

Distributed by:

Zydus Pharmaceuticals USA Inc.

Pennington, NJ 08534

Rev.: 07/16

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:

• Increased risk of a heart attack or stroke that can lead to death . This risk may happen early in treatment and may increase:

o with increasing doses of NSAIDs

o with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a "coronary artery

bypass graft (CABG)."

Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:

o   anytime during use

o   without warning symptoms

o   that may cause death

The risk of getting an ulcer or bleeding increases with:

o  past history of stomach ulcers, or stomach or intestinal bleeding with use of

    NSAIDs

o  taking medicines called "corticosteroids", "anticoagulants", "SSRIs", or "SNRIs"

o  increasing doses of NSAIDs

o  older age

o  longer use of NSAIDs

o  poor health o smoking

o  advanced liver disease

o  drinking alcohol

o  bleeding problems

NSAIDs should only be used:

o  exactly as prescribed

o  at the lowest dose possible for your treatment

o  for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?

Do not take NSAIDs:

• if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.
• right before or after heart bypass surgery.

Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:

• have liver or kidney problems
• have high blood pressure
• have asthma
• are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy.
• are breastfeeding or plan to breast feed.

Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements.

NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

What are the possible side effects of NSAIDs?

NSAIDs can cause serious side effects, including:

See "What is the most important information I should know about medicines called

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?"

• new or worse high blood pressure
• heart failure
• liver problems including liver failure
• kidney problems including kidney failure
• low red blood cells (anemia)
• life-threatening skin reactions
• life-threatening allergic reactions
• Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas,
• heartburn, nausea, vomiting, and dizziness.

Get emergency help right away if you get any of the following symptoms:

shortness of breath or trouble breathing

• slurred speech
• chest pain
• swelling of the face or throat
• weakness in one part or side of your body

Stop taking your NSAID and call your healthcare provider right away if you get any

of the following symptoms:

• nausea
• vomit blood
• more tired or weaker than usual
• there is blood in your bowel movement or it is
• diarrhea black and sticky like tar
• itching
• unusual weight gain
• your skin or eyes look yellow
• skin rash or blisters with fever
• indigestion or stomach pain
• swelling of the arms, legs, hands and feet
• flu-like symptoms

If you take too much of your NSAID, call your healthcare provider or get medical

help right away.

These are not all the possible side effects of NSAIDs. For more information, ask your

healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to

FDA at 1-800-FDA-1088.

Other information about NSAIDs:

• Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
• Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

General information about the safe and effective use of NSAIDs Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.

Please address medical inquiries to, (MedicalAffairs@zydususa.com) Tel.: 1-877-993-8779.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

This product's label may have been updated. For current full prescribing information,

please visit www.zydususa.com.

Manufactured by:

Cadila Healthcare Ltd.

India.

Distributed by:

Zydus Pharmaceuticals USA Inc.

Pennington, NJ 08534

Rev.: 07/16

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Distribution

Children 2 to 6 years (n=7): Apparent Vd: 0.19 L/kg (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): Apparent Vd: 0.13 L/kg (Burgos-Vargas 2004)

Adults: Vdss~10 L

Metabolism

Hepatic via CYP2C9 and CYP3A4 (minor); forms 4 metabolites (inactive)

Excretion

Urine and feces (as inactive metabolites); <1% excreted unchanged in urine

Clearance:

Children 2 to 6 years (n=7): 0.17 mL/minute/kg (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): 0.12 mL/minute/kg (Burgos-Vargas 2004)

Adults: 7 to 9 mL/minute

Time to Peak

Children and Adolescents 2 to 16 years (n=18): Suspension: Initial: 1 to 3 hours; secondary: 6 to 12 hours (Burgos-Vargas 2004)

Adults: Initial: Within 2 hours (capsule); 4 to 5 hours (tablet); Secondary: ~8 hours (capsule); 12 to 14 hours (tablet)

Half-Life Elimination

Children 2 to 6 years (n=7): 13.4 hours (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): 12.7 hours (Burgos-Vargas 2004)

Adults: ~15 to 22 hours

Protein Binding

~99%, primarily to albumin; Note: Free fraction was higher in adult patients with renal failure who were receiving chronic dialysis.

US labeling:

CrCl ≥20 mL/minute: No dosage adjustment necessary.

CrCl <20 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use is not recommended.

Hemodialysis (not dialyzable): Use with caution and monitor closely. Maximum dose: 7.5 mg/day (tablet/suspension); 5 mg/day (capsule). Note: Additional dose not necessary after hemodialysis.

Canadian labeling:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute or deteriorating renal function: Use is contraindicated.

Hemodialysis (not dialyzable): Maximum dose: 7.5 mg/day. Note: Additional dose not necessary after hemodialysis.

KDIGO 2012 guidelines provide the following recommendations for NSAIDs:

eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016)

Percentages reported in adult patients. Reactions similar in pediatric patients; abdominal pain, diarrhea, fever, headache, pyrexia, and vomiting were reported more commonly than in adult patients.

1% to 10%:

Cardiovascular: Edema (≤5%), angina pectoris (<2%), cardiac arrhythmia (<2%), cardiac failure (<2%), facial edema (<2%), hypertension (<2%), hypotension (<2%), myocardial infarction (<2%), palpitations (<2%), paresthesia (<2%), syncope (<2%), tachycardia (<2%), vasculitis (<2%)

Central nervous system: Pain (≤5%), headache (2% to 4%), dizziness (1% to 4%), insomnia (≤4%), falling (1% to 3%), abnormal dreams (<2%), anxiety (<2%), confusion (<2%), convulsions (<2%), depression (<2%), drowsiness (<2%), fatigue (<2%), malaise (<2%), nervousness (<2%), vertigo (<2%)

Dermatologic: Skin rash (≤3%), pruritus (≤2%), bullous rash (<2%), diaphoresis (<2%), skin photosensitivity (<2%), urticaria (<2%)

Endocrine & metabolic: Albuminuria (<2%), dehydration (<2%), hot flash (<2%), increased gamma-glutamyl transferase (<2%), weight gain (<2%), weight loss (<2%)

Gastrointestinal: Dyspepsia (4% to 10%), diarrhea (2% to 8%), nausea (2% to 7%), abdominal pain (2% to 5%), constipation (≤3%), flatulence (≤3%), vomiting (≤3%), aphthous stomatitis (<2%), colitis (<2%), duodenal ulcer (<2%), dysgeusia (<2%), eructation (<2%), esophagitis (<2%), gastrointestinal perforation (<2%; including duodenal, gastric), gastric ulcer (<2%), gastritis (<2%), gastroesophageal reflux disease (<2%), gastrointestinal hemorrhage (<2%), hematemesis (<2%), increased appetite (<2%), intestinal perforation (<2%), melena (<2%), pancreatitis (<2%), xerostomia (<2%)

Genitourinary: Urinary tract infection (≤7%), urinary frequency (≤2%), hematuria (<2%)

Hematologic & oncologic: Anemia (≤4%), leukopenia (<2%), purpura (<2%), thrombocytopenia (<2%)

Hepatic: Hepatitis (<2%), hyperbilirubinemia (<2%), increased serum ALT (<2%), increased serum AST (<2%)

Hypersensitivity: Angioedema (<2%), hypersensitivity reaction (<2%)

Neuromuscular & skeletal: Arthralgia (≤5%), back pain (≤3%), tremor (<2%)

Ophthalmic: Conjunctivitis (<2%), visual disturbance (<2%)

Otic: Tinnitus (<2%)

Renal: Increased blood urea nitrogen (<2%), increased serum creatinine (<2%), renal failure (<2%)

Respiratory: Upper respiratory tract infection (≤8%), flu-like symptoms (3% to 6%), pharyngitis (3%), cough (≤2%), asthma (<2%)

Miscellaneous: Fever (<2%)

<2% (Limited to important or life-threatening): Agranulocytosis, anaphylactoid reaction, anaphylaxis, erythema multiforme, exfoliative dermatitis, hepatic failure, hepatotoxicity (idiosyncratic) (Chalasani 2014), interstitial nephritis, jaundice, renal insufficiency, renal papillary necrosis, shock, Stevens-Johnson syndrome, toxic epidermal necrolysis

Meloxicam can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Do not use this medicine just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

Meloxicam may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using meloxicam, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

Avoid drinking alcohol. It may increase your risk of stomach bleeding.

Ask a doctor or pharmacist before using any other cold, allergy, or pain medicine. Medicines similar to meloxicam are contained in many combination medicines. Check the label to see if a medicine contains an NSAID (non-steroidal anti-inflammatory drug) such as aspirin, ibuprofen, ketoprofen, or naproxen.

Meloxicam can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Even people without heart disease or risk factors could have a stroke or heart attack while taking this medicine.

Do not use this medicine just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Meloxicam may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using meloxicam, especially in older adults.

You should not use meloxicam if you are allergic to it, or if you have ever had an asthma attack or severe allergic reaction after taking aspirin or an NSAID.

To make sure meloxicam is safe for you, tell your doctor if you have:

• heart disease, high blood pressure, high cholesterol, diabetes, or if you smoke;

• a history of heart attack, stroke, or blood clot;

• a history of stomach ulcers or bleeding;

• asthma;

• kidney disease (or if you are on dialysis);

• liver disease; or

• fluid retention.

Taking meloxicam during the last 3 months of pregnancy may harm the unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Meloxicam may cause a delay in ovulation (the release of an egg from an ovary). You should not take this medicine if you are undergoing fertility treatment, or are otherwise trying to get pregnant.

Meloxicam can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Meloxicam is not approved for use by anyone younger than 2 years old.

Ask your doctor before using meloxicam if you take an antidepressant such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone. Taking any of these medicines with an NSAID may cause you to bruise or bleed easily.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• cyclosporine;

• lithium;

• methotrexate;

• sodium polystyrene sulfonate (Kayexalate);

• a blood thinner (warfarin, Coumadin, Jantoven);

• heart or blood pressure medication, including a diuretic or "water pill"; or

• steroid medicine (such as prednisone).

This list is not complete. Other drugs may interact with meloxicam, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Oral Suspension and Tablets:
-Initial dose: 7.5 mg orally once a day
-Maintenance dose: 15 mg orally once a day in patients requiring additional analgesia
-Maximum dose: 15 mg orally once a day

Comment:
-The lowest effective dose for the shortest duration possible consistent with individual treatment goals should be used.

Use: For the relief of signs and symptoms of rheumatoid arthritis

US BOXED WARNINGS: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS:
-Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
-This drug is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
-NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 and patients with a prior history of peptic ulcer disease and/or GI bleeding are at a greater risk for serious GI events.

Oral Tablets and Suspension:
-Safety and efficacy have not been established in patients younger than 2 years.

Oral Capsules:
-Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Stomach-related side effects including indigestion, heartburn, and bleeding. People of an older age, taking other medicines that affect the stomach, or who drink more than 3 glasses of alcohol per day may be more at risk. Meloxicam is considered to have a low potential for stomach-related side effects compared with other NSAIDs.
• Most NSAIDs have been associated with an increased risk of stroke or heart attack. The risk may be higher in patients with preexisting cardiovascular conditions and with higher dosages.
• May not be suitable for some people including those with kidney disease, a history of stomach ulcers or other gastrointestinal disorders, with pre-existing cardiovascular disease, or following coronary artery bypass graft surgery.
• May interact with some other medicines such as warfarin, SSRIs, ACE inhibitors, and diuretics.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

• Peak concentrations reached within 2 hours (capsule) and 4 to 5 hours (tablets). Meloxicam appears to be recycled in the liver so another peak is reached in 8 hours (capsule) or in 12-14 hours (tablet) after the initial dose.

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