Label: MELOXICAM tablet
Contains inactivated NDC Code(s)
NDC Code(s): 52959-857-00, 52959-857-07, 52959-857-14, 52959-857-15, view more52959-857-20, 52959-857-21, 52959-857-30, 52959-857-40, 52959-857-45, 52959-857-60, 52959-857-90
- Packager: H.J. Harkins Company, Inc.
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: Abbreviated New Drug Application
Updated August 28, 2018
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WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular 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 [see Warnings and Precautions (5.1) ].
Meloxicam tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) and Warnings and Precautions (5.1) ].
Gastrointestinal Bleeding, Ulceration, and Perforation
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 greater risk for serious GI events [see Warnings and Precautions (5.2) ].
INDICATIONS & USAGE
1.1 Osteoarthritis (OA)
Meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [see Clinical Studies (14.1)].
1.2 Rheumatoid Arthritis (RA)
Meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [see Clinical Studies (14.1)].
1.3 Juvenile Rheumatoid Arthritis (JRA) Pauciarticular and Polyarticular Course
Meloxicam tablets are indicated for relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients who weigh ≥60 kg [see Dosage and Administration (2.4) and Clinical Studies (14.2)].
DOSAGE & ADMINISTRATION
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 [see Warnings and Precautions (5)].
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 [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Meloxicam tablets may be taken without regard to timing of meals.
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 tablets 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 tablets in subjects with severe renal impairment is not recommended.
In patients on hemodialysis, the maximum dosage of Meloxicam tablets is 7.5 mg per day [see Clinical Pharmacology (12.3)].
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.
Meloxicam tablets are contraindicated in the following patients:
Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [see Warnings and Precautions (5.7, 5.9) ]
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 [see Warnings and Precautions (5.7, 5.8) ]
In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ]
WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as meloxicam, increases the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)].
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications (4)].
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of Meloxicam in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Meloxicam is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
5.2 Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs, including meloxicam, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.
Risk Factors for GI Bleeding, Ulceration, and Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
Strategies to Minimize the GI Risks in NSAID-treated patients:
Use the lowest effective dosage for the shortest possible duration.
Avoid administration of more than one NSAID at a time.
Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Meloxicam until a serious GI adverse event is ruled out.
In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding [see Drug Interactions (7) ].
Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.
Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including meloxicam.
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 clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Meloxicam immediately, and perform a clinical evaluation of the patient [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
NSAIDs, including Meloxicam, can lead to new onset or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [see Drug Interactions (7)].
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
5.5 Heart Failure and Edema
The Coxib and traditional NSAID Trialists' Collaboration meta analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of meloxicam may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see Drug Interactions (7)].
Avoid the use of Meloxicam in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Meloxicam is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
5.6 Renal Toxicity and Hyperkalemia
Long-term administration of NSAIDs, including Meloxicam, has resulted in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
The renal effects of Meloxicam may hasten the progression of renal dysfunction in patients with preexisting renal disease. Because some Meloxicam metabolites are excreted by the kidney, monitor patients for signs of worsening renal function.
Correct volume status in dehydrated or hypovolemic patients prior to initiating Meloxicam. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Meloxicam [see Drug Interactions (7)].
No information is available from controlled clinical studies regarding the use of Meloxicam in patients with advanced renal disease. Avoid the use of Meloxicam in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Meloxicam is used in patients with advanced renal disease, monitor patients for signs of worsening renal function [see Clinical Pharmacology (12.3)].
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
5.7 Anaphylactic Reactions
Meloxicam has been associated with anaphylactic reactions in patients with and without known hypersensitivity to meloxicam and in patients with aspirin-sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.8)].
Seek emergency help if an anaphylactic reaction occurs.
5.8 Exacerbation of Asthma Related to Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Meloxicam is contraindicated in patients with this form of aspirin sensitivity [see Contraindications (4)]. When Meloxicam is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
5.9 Serious Skin Reactions
NSAIDs, including meloxicam, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Meloxicam at the first appearance of skin rash or any other sign of hypersensitivity. Meloxicam is contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4)].
5.10 Premature Closure of Fetal Ductus Arteriosus
Meloxicam may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Meloxicam, in pregnant women starting at 30 weeks of gestation (third trimester) [see Use in Specific Populations (8.1)].
5.11 Hematologic Toxicity
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Meloxicam has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Meloxicam, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions (7)].
5.12 Masking of Inflammation and Fever
The pharmacological activity of Meloxicam in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
5.13 Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].
USE IN SPECIFIC POPULATIONS
Use of NSAIDs, including Meloxicam, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Meloxicam, in pregnant women starting at 30 weeks of gestation (third trimester) [see Warnings and Precautions (5.10)].
There are no adequate and well-controlled studies of Meloxicam in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss.
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 [see Data].
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.
Labor or Delivery
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.
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 (0.65and 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).
There are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Meloxicam and any potential adverse effects on the breastfed infant from the Meloxicam or from the underlying maternal condition.
Meloxicam was present in the milk of lactating rats at concentrations higher than those in plasma.
8.3 Females and Males of Reproductive Potential
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.
8.4 Pediatric Use
The safety and effectiveness of meloxicam in pediatric JRA patients from 2 to 17 years of age has been evaluated in three clinical trials [see Dosage and Administration (2.3), Adverse Reactions (6.1) and Clinical Studies (14.2)].
8.5 Geriatric Use
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 [see Warnings and Precautions (5.1, 5.2, 5.3, 5.6, 5.13)].
8.6 Hepatic Impairment
No dose adjustment is necessary in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment have not been adequately studied. Since meloxicam is significantly metabolized in the liver and hepatotoxicity may occur, use meloxicam with caution in patients with hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].
8.7 Renal Impairment
No dose adjustment is necessary in patients with mild to moderate renal impairment. Patients with severe renal impairment have not been studied. The use of Meloxicam in subjects with severe renal impairment is not recommended. In patients on hemodialysis, meloxicam should not exceed 7.5 mg per day. Meloxicam is not dialyzable [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
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 [see Warnings and Precautions (5.1, 5.2, 5.4, 5.6)].
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 (1-800-222-1222).
Meloxicam Tablets USP are a nonsteroidal anti-inflammatory drug (NSAID). Each tablet 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)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide. The molecular weight is 351.4. Its empirical formula is C14H13N3O4S2 and it has the following structural formula:
Meloxicam is a pastel yellow solid, practically insoluble in water, with higher solubility observed in strong acids and bases. It is very slightly soluble in methanol. Meloxicam has an apparent partition coefficient (log P)app = 0.1 in n-octanol/buffer pH 7.4. Meloxicam has pKa values of 1.1 and 4.2.
Meloxicam is available as a tablet 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.
14.1 Osteoarthritis and Rheumatoid Arthritis
The use of Meloxicam 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. Meloxicam (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 Meloxicam 7.5 mg daily and Meloxicam 15 mg daily showed significant improvement in each of these endpoints compared with placebo.
The use of Meloxicam 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 Meloxicam, 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 Meloxicam for the treatment of the signs and symptoms of rheumatoid arthritis was evaluated in a 12-week, double-blind, controlled multinational trial. Meloxicam (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 Meloxicam 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.
14.2 Juvenile Rheumatoid Arthritis (JRA) Pauciarticular and Polyarticular Course
The use of Meloxicam 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.
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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)].
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 tablets 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)].
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 tablets immediately if they develop any type of rash and to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.9)].
Advise females of reproductive potential who desire pregnancy that NSAIDs, including Meloxicam tablets, may be associated with a reversible delay in ovulation [see Use in Specific Populations (8.3)].
Inform pregnant women to avoid use of Meloxicam tablets 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 tablets 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 tablets until they talk to their healthcare provider [see Drug Interactions (7)].
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 longer use of NSAIDs
o drinking alcohol
o older age
o poor health
o advanced liver disease
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
• chest pain
• weakness in one part or side of your body
• slurred speech
• swelling of the face or throat
Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:
• more tired or weaker than usual
• your skin or eyes look yellow
• indigestion or stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or blisters with fever
• swelling of the arms, legs, hands and feet
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.
- PRINCIPAL DISPLAY PANEL
INGREDIENTS AND APPEARANCE
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:52959-857 Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MELOXICAM (UNII: VG2QF83CGL) (MELOXICAM - UNII:VG2QF83CGL) MELOXICAM 15 mg Product Characteristics Color yellow Score no score Shape OVAL Size 12mm Flavor Imprint Code U;L;15 Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:52959-857-07 7 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 2 NDC:52959-857-14 14 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 3 NDC:52959-857-15 15 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 4 NDC:52959-857-20 20 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 5 NDC:52959-857-21 21 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 6 NDC:52959-857-30 30 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 7 NDC:52959-857-40 40 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 8 NDC:52959-857-45 45 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 9 NDC:52959-857-60 60 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 10 NDC:52959-857-90 90 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 11 NDC:52959-857-00 100 in 1 VIAL, PLASTIC; Type 0: Not a Combination Product 04/08/2014 Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077927 04/08/2014 Labeler - H.J. Harkins Company, Inc. (147681894) Establishment Name Address ID/FEI Business Operations H.J. Harkins Company, Inc. 147681894 manufacture(52959-857) , relabel(52959-857) , repack(52959-857)