MELOX

Meloxicam, is a nonsteroidal anti-inflammatory drug (NSAID).

Each light yellow meloxicam tablet

USP contains 7.5 mg or 15 mg meloxicam for oral administration.

Meloxicam is chemically designated as 4-hydroxy-2-methyl.

• N -(5-methyl-2-thiazolyl)-2 H -1,2-benzothiazine-3-carboxamide-1,1-dioxide.

The molecular weight is 351.4.

Its empirical formula is

C 14 H 13 N 3 O 4 S 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.

Meloxicam tablets

USP are available as tablets for oral administration containing 7.5 mg or 15 mg meloxicam.

The inactive ingredients in meloxicam tablets

USP include colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium citrate dihydrate. image 01.

Melukiskam is used as a painkiller and a hypothermic.

The treatment of congenital arthritis.

If the patient has to undergo surgery, treatment must be stopped well in advance of the surgery.

Older persons, because of their increased sensitivity to the side effects that the treatment may cause.

Meloxicam can cause an increased risk of heart attack or stroke, especially with prolonged use, high doses, or if the patient suffers from heart and arterial diseases.

Meloxicam may cause bleeding in the digestive system, especially in the case of older persons.

It is recommended that alcohol and smoking be avoided during the use of this drug, since the risk of bleeding of the stomach is increased by smoking and alcohol.

Meluxicam is a disease of the carrier and the nurse.

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

The mechanism of action of meloxicam, 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. 12.3 Pharmacokinetics Absorption 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 C max 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 to 14 hours post-dose suggesting biliary recycling.

Meloxicam oral suspension doses of 7.5 mg/5mL 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 meloxicam tablets.

Table 4 Single Dose and Steady-State Pharmacokinetic Parameters for Oral 7.5 mg and 15 mg Meloxicam (Mean and % CV) The parameter values in the table are from various studies Steady State Single Dose Pharmacokinetic Parameters (% CV ) Healthy male adults ( Fed ) not under high fat conditions Elderly males ( Fed ) Elderly females ( Fed ) Renal failure ( Fasted ) Hepatic insufficiency ( Fasted ) 7. 5 mg meloxicam tablets tablets 15 mg capsules 15 mg capsules 15 mg capsules 15 mg capsules N 18 5 8 12 12 C m a x [μg/mL] 1.05 2.3 3.2 0.59 0.84 t m a x [h] 4.9 5 6 4 10 t 1 / 2 [h] 20.1 21 24 18 16 CL/f [mL/min] 8.8 9.9 5.1 19 11 V z /f V z /f =Dose/(AUC•K e l ) [L] 14.7 15 10 26 14 Food and Antacid Effects: Administration of meloxicam capsules following a high fat breakfast (75 g of fat) resulted in mean peak drug levels (i.e., C max ) being increased by approximately 22% while the extent of absorption (AUC) was unchanged.

The time to maximum concentration (T max ) was achieved between and 6 hours.

In comparison, neither the AUC nor the C max values for meloxicam suspension were affected following a similar high fat meal, while mean T max values were increased to approximately 7 hours.

No pharmacokinetic interaction was detected with concomitant administration of antacids.

Based on these results, meloxicam 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.

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.

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 (t 1/2 ) 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 to 9 mL/min. Specific Populations Pediatric: 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.

The meloxicam mean (SD) elimination half-life was 15.2 and 13.0 hours for the to 6 year old patients, and 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 meloxicam 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 AUC ss and 32% higher C max,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 meloxicam, 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 C max or T max 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.

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 meloxicam in subjects with severe renal impairment is not recommended.

Following a single dose of meloxicam, the free C max 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.

When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered.

When meloxicam is administered with aspirin (1000 mg three times daily) to healthy volunteers, it tended to increase the AUC (10%) and C max (24%) of meloxicam.

The clinical significance of this interaction is not known.

See Table for clinically significant drug interactions of NSAIDs with aspirin.

Pretreatment for four days with cholestyramine significantly increased the clearance of meloxicam by 50%.

This resulted in a decrease in t 1/2, 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.

Concomitant administration of 200 mg cimetidine four times daily did not alter the single-dose pharmacokinetics of 30 mg meloxicam.

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.

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 to 1072 mg twice daily with meloxicam 15 mg QD every day as compared to subjects receiving lithium alone.

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.

The effect of meloxicam on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of warfarin that prod.

Meluxicum belongs to a group of treatments called anti-steroid anti-inflammation, which discourage the work of an enzyme called an enzyme of throat oxidation, which is responsible for the manufacture of inflammation.

• and pain-inflammation-related substances.

Meluxicam has an effect on pain, heat-free, and anti-inflammation.

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Most common (≥5% and greater than placebo) adverse events in adults are diarrhea, upper respiratory tract infections, dyspepsia, and influenza-like symptoms Adverse events observed in pediatric studies were similar in nature to the adult clinical trial experience To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.fda.gov/medwatch.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events GI Bleeding, Ulceration, and Perforation Hepatotoxicity Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylactic Reactions Serious Skin Reactions Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Fetal Toxicity Hematologic Toxicity 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The meloxicam Phase 2/3 clinical trial database includes 10,122 OA patients and 1012 RA patients treated with meloxicam 7.5 mg/day, 3505 OA patients and 1351 RA patients treated with meloxicam 15 mg/day. Meloxicam at these doses was administered to 661 patients for at least 6 months and to 312 patients for at least one year.

Approximately of these patients were treated in ten placebo.

• and/or active-controlled osteoarthritis trials and of these patients were treated in ten placebo.

• and/or active-controlled rheumatoid arthritis trials.

Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across meloxicam trials.

A 12-week multicenter, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of meloxicam with placebo and with an active control.

Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of meloxicam with placebo.

Table 1a depicts adverse events that occurred in ≥2% of the meloxicam treatment groups in a 12-week placebo.

• and active-controlled osteoarthritis trial.

Table 1b depicts adverse events that occurred in ≥2% of the meloxicam treatment groups in two 12-week placebo-controlled rheumatoid arthritis trials.

Table 1a Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in a 12-Week Osteoarthritis Placebo.

• and Active-Controlled Trial Placebo Meloxicam 7. 5 mg daily Meloxicam 15 mg daily Diclofenac 100 mg daily No. of Patients 157 154 156 153 Gastrointestinal 17.2 20.1 17.3 28.1 Abdominal pain 2.5 1.9 2.6 1.3 Diarrhea 3.8 7.8 3.2 9.2 Dyspepsia 4.5 4.5 4.5 6.5 Flatulence 4.5 3.2 3.2 3.9 Nausea 3.2 3.9 3.8 7.2 Body as a Whole Accident household 1.9 4.5 3.2 2.6 Edema WHO preferred terms edema, edema dependent, edema peripheral, and edema legs combined 2.5 1.9 4.5 3.3 Fall 0.6 2.6 0.0 1.3 Influenza-like symptoms 5.1 4.5 5.8 2.6 Central and Peripheral Nervous System Dizziness 3.2 2.6 3.8 2.0 Headache 10.2 7.8 8.3 5.9 Respiratory Pharyngitis 1.3 0.6 3.2 1.3 Upper respiratory tract infection 1.9 3.2 1.9 3.3 Skin Rash WHO preferred terms rash, rash erythematous, and rash maculo-papular combined 2.5 2.6 0.6 2.0 Table 1b Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in two 12-Week Rheumatoid Arthritis Placebo-Controlled Trials Placebo Meloxicam 7. 5 mg daily Meloxicam 15 mg daily No. of Patients 469 481 477 Gastrointestinal.

Disorders 14.1 18.9 16.8 Abdominal pain NOS MedDRA preferred term: nausea, abdominal pain NOS, influenza-like illness, headaches NOS, and rash NOS 0.6 2.9 2.3 Dyspeptic signs and symptoms MedDRA high level term (preferred terms): dyspeptic signs and symptoms (dyspepsia, dyspepsia aggravated, eructation, gastrointestinal irritation), upper respiratory tract infections-pathogen unspecified (laryngitis NOS, pharyngitis NOS, sinusitis NOS), joint related signs and symptoms (arthralgia, arthralgia aggravated, joint crepitation, joint effusion, joint swelling) 3.8 5.8 4.0 Nausea 2.6 3.3 3.8 General.

Disorders and Administration Site Conditions Influenza-like illness 2.1 2.9 2.3 Infection and Infestations Upper respiratory tract infections-pathogen class unspecified 4.1 7.0 6.5 Musculoskeletal and Connective Tissue.

Disorders Joint related signs and symptoms 1.9 1.5 2.3 Nervous System.

Disorders Headaches NOS 6.4 6.4 5.5 Skin and Subcutaneous Tissue.

Disorders Rash NOS 1.7 1.0 2.1 The adverse events that occurred with meloxicam in ≥2% of patients treated short-term (4 to 6 weeks) and long-term (6 months) in active-controlled osteoarthritis trials are presented in Table 2.

Table 2 Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials to 6 Weeks Controlled Trials 6 Month Controlled Trials Meloxicam 7. 5 mg daily Meloxicam 15 mg daily Meloxicam 7. 5 mg daily Meloxicam 15 mg daily No. of Patients 8955 256 169 306 Gastrointestinal 11.8 18.0 26.6 24.2 Abdominal pain 2.7 2.3 4.7 2.9 Constipation 0.8 1.2 1.8 2.6 Diarrhea 1.9 2.7 5.9 2.6 Dyspepsia 3.8 7.4 8.9 9.5 Flatulence 0.5 0.4 3.0 2.6 Nausea 2.4 4.7 4.7 7.2 Vomiting 0.6 0.8 1.8 2.6 Body as a Whole Accident household 0.0 0.0 0.6 2.9 Edema WHO preferred terms edema, edema dependent, edema peripheral, and edema legs combined 0.6 2.0 2.4 1.6 Pain 0.9 2.0 3.6 5.2 Central and Peripheral Nervous System Dizziness 1.1 1.6 2.4 2.6 Headache 2.4 2.7 3.6 2.6 Hematologic Anemia 0.1 0.0 4.1 2.9 Musculoskeletal Arthralgia 0.5 0.0 5.3 1.3 Back pain 0.5 0.4 3.0 0.7 Psychiatric Insomnia 0.4 0.0 3.6 1.6 Respiratory Coughing 0.2 0.8 2.4 1.0 Upper respiratory tract infection 0.2 0.0 8.3 7.5 Skin Pruritus 0.4 1.2 2.4 0.0 Rash WHO preferred terms rash, rash erythematous, and rash maculo-papular combined 0.3 1.2 3.0 1.3 Urinary Micturition frequency 0.1 0.4 2.4 1.3 Urinary tract infection 0.3 0.4 4.7 6.9 Higher doses of meloxicam (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore, the daily dose of meloxicam should not exceed 15 mg. Pediatrics Pauciarticular and Polyarticular Course Juvenile Rheumatoid Arthritis (JRA): Three hundred and eighty-seven patients with pauciarticular and polyarticular course JRA were exposed to meloxicam with doses ranging from 0.125 to 0.375 mg/kg per day in three clinical trials.

These studies consisted of two 12-week multicenter, double-blind, randomized trials (one with a 12-week open-label extension and one with a 40-week extension) and one 1-year open-label PK study.

The adverse events observed in these pediatric studies with meloxicam were similar in nature to the adult clinical trial experience, although there were differences in frequency.

In particular, the following most common adverse events, abdominal pain, vomiting, diarrhea, headache, and pyrexia, were more common in the pediatric than in the adult trials.

Rash was reported in seven (<2%) patients receiving meloxicam.

No unexpected adverse events were identified during the course of the trials.

The adverse events did not demonstrate an age or gender-specific subgroup effect.

The following is a list of adverse drug reactions occurring in <2% of patients receiving meloxicam in clinical trials involving approximately 16,200 patients.

Body as a

Whole allergic reaction, face edema, fatigue, fever, hot flushes, malaise, syncope, weight decrease, weight increase Cardiovascular angina pectoris, cardiac failure, hypertension, hypotension, myocardial infarction, vasculitis Central and Peripheral Nervous System convulsions, paresthesia, tremor, vertigo Gastrointestinal colitis, dry mouth, duodenal ulcer, eructation, esophagitis, gastric ulcer, gastritis, gastroesophageal reflux, gastrointestinal hemorrhage, hematemesis, hemorrhagic duodenal ulcer, hemorrhagic gastric ulcer, intestinal perforation, melena, pancreatitis, perforated duodenal ulcer, perforated gastric ulcer, stomatitis ulcerative Heart Rate and Rhythm arrhythmia, palpitation, tachycardia Hematologic leukopenia, purpura, thrombocytopenia Liver and Biliary System ALT increased, AST increased, bilirubinemia, GGT increased, hepatitis Metabolic and Nutritional dehydration Psychiatric abnormal dreaming, anxiety, appetite increased, confusion, depression, nervousness, somnolence Respiratory asthma, bronchospasm, dyspnea Skin and Appendages alopecia, angioedema, bullous eruption, photosensitivity reaction, pruritus, sweating increased, urticaria Special Senses abnormal vision, conjunctivitis, taste perversion, tinnitus Urinary System albuminuria, BUN increased, creatinine increased, hematuria, renal failure 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of meloxicam.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Decisions about whether to include an adverse event from spontaneous reports in labeling are typically based on one or more of the following factors: seriousness of the event, number of reports, or strength of causal relationship to the drug.

Adverse reactions reported in worldwide postmarketing experience or the literature include: acute urinary retention; agranulocytosis; alterations in mood (such as mood elevation); anaphylactoid reactions including shock; erythema multiforme; exfoliative dermatitis; interstitial nephritis; jaundice; liver failure; Stevens-Johnson syndrome; fixed drug eruption (FDE); toxic epidermal necrolysis, and infertility female.

Symptoms following acute

NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care.

Gastrointestinal bleeding has occurred.

Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare.

Manage patients with symptomatic and supportive care following an NSAID overdosage.

There are no specific antidotes.

Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage).

Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

There is limited experience with meloxicam overdosage.

Cholestyramine is known to accelerate the clearance of meloxicam.

Accelerated removal of meloxicam by 4 g oral doses of cholestyramine given three times a day was demonstrated in a clinical trial.

Administration of cholestyramine may be useful following an overdosage.

For additional information about overdosage treatment, call a poison control center.

Meloxicam is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients In the setting of coronary artery bypass graft (CABG) surgery Known hypersensitivity to meloxicam or any components of the drug product History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs In the setting of CABG surgery.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals OA and RA: Starting dose: 7.5 mg once daily Dose may be increased to 15 mg once daily JRA: 7.5 mg once daily in children ≥60 kg Meloxicam Tablets are not interchangeable with approved formulations of oral meloxicam even if the total milligram strength is the same 2.1 General Dosing Instructions Carefully consider the potential benefits and risks of meloxicam tablets and other treatment options before deciding to use meloxicam tablets.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

After observing the response to initial therapy with meloxicam tablets, adjust the dose to suit an individual patient's needs.

In adults, the maximum recommended daily oral dose of meloxicam tablets is 15 mg regardless of formulation.

In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended.

Meloxicam tablets may be taken without regard to timing of meals. 2.2 Osteoarthritis For the relief of the signs and symptoms of osteoarthritis the recommended starting and maintenance oral dose of meloxicam tablets is 7.5 mg once daily.

Some patients may receive additional benefit by increasing the dose to 15 mg once daily. 2.3 Rheumatoid Arthritis For the relief of the signs and symptoms of rheumatoid arthritis, the recommended starting and maintenance oral dose of meloxicam tablets is 7.5 mg once daily.

Some patients may receive additional benefit by increasing the dose to 15 mg once daily. 2.4 Juvenile Rheumatoid Arthritis (JRA) Pauciarticular and Polyarticular Course For the treatment of juvenile rheumatoid arthritis, the recommended oral dose of meloxicam is 7.5 mg once daily in children who weigh ≥60 kg. There was no additional benefit demonstrated by increasing the dose above 7.5 mg in clinical trials.

Meloxicam tablets should not be used in children who weigh <60 kg. 2.5 Renal Impairment The use of meloxicam in subjects with severe renal impairment is not recommended.

In patients on hemodialysis, the maximum dosage of meloxicam is 7.5 mg per day. 2.6 Non-Interchangeability with Other Formulations of Meloxicam Meloxicam Tablets have not shown equivalent systemic exposure to other approved formulations of oral meloxicam.

Therefore, Meloxicam Tablets are not interchangeable with other formulations of oral meloxicam product even if the total milligram strength is the same.

Do not substitute similar dose strengths of Meloxicam Tablets with other formulations of oral meloxicam product.

USP are available as light yellow coloured, round, biconvex tablets, plain on one side and debossed with '7.5' on other side containing meloxicam 7.5 mg or as light yellow coloured, oval shaped, biconvex tablets, plain on one side and debossed with '15' on other side containing meloxicam 15 mg. Meloxicam Tablets USP, 7.5 mg are available as follows: Bottles of 100 NDC 68180-501-01 Bottles of 1000 NDC 68180-501-03 Meloxicam Tablets USP, 15 mg are available as follows: Bottles of 100 NDC 68180-502-01 Bottles of 1000 NDC 68180-502-03 Storage Store at 20° to 25°C (68° to 77°F) .

Keep meloxicam tablets

USP in a dry place.

Dispense tablets in a tight container.

Keep this and all medications out of the reach of children.

Risk Summary Use of

NSAIDs, including meloxicam, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

Because of these risks, limit dose and duration of meloxicam use between about and 30 weeks of gestation, and avoid meloxicam use at about 30 weeks of gestation and later in pregnancy.

Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including meloxicam, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive.

In animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.65.

• and 6.5-times the maximum recommended human dose (MRHD) of meloxicam.

Increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 78-times the MRHD.

In pre.

• and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.08-times MRHD of meloxicam.

No teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2.6 and 26-times the MRHD.

Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization.

In animal studies, administration of prostaglandin synthesis inhibitors such as meloxicam, resulted in increased pre.

• and post-implantation loss.

Prostaglandins also have been shown to have an important role in fetal kidney development.

In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including meloxicam, can cause premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible.

If meloxicam treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios.

If oligohydramnios occurs, discontinue meloxicam and follow up according to clinical practice.

There are no studies on the effects of meloxicam during labor or delivery.

In animal studies, NSAIDs, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.

Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug.

There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible.

Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.

Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications.

These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use.

Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full.

• term infant exposed to NSAIDs through maternal use is uncertain.

Meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the MRHD of 15 mg of meloxicam based on BSA comparison).

Administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (78-fold greater than the MRHD based on BSA comparison).

The no effect level was 20 mg/kg/day (26-fold greater than the MRHD based on BSA conversion).

In rats and rabbits, embryolethality occurred at oral meloxicam doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65-and 6.5-fold greater, respectively, than the MRHD based on BSA comparison) when administered throughout organogenesis.

Oral administration of meloxicam to pregnant rats during late gestation through lactation increased the incidence of dystocia, delayed parturition, and decreased offspring survival at meloxicam doses of 0.125 mg/kg/day or greater (0.08-times MRHD based on BSA comparison).

Females and Males of Reproductive Potential Infertility Females: Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including meloxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women.

Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation.

Small studies in women treated with

NSAIDs have also shown a reversible delay in ovulation.

Consider withdrawal of

NSAIDs, including meloxicam, in women who have difficulties conceiving or who are undergoing investigation of infertility.

The safety and effectiveness of meloxicam in pediatric JRA patients from to 17 years of age has been evaluated in three clinical trials.

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions.

If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.