Meloxicam is a non-steroidal anti-inflammatory drug indicated for: Osteoarthritis (OA) ( 1.1 ) Rheumatoid Arthritis (RA) ( 1.2 ) Juvenile Rheumatoid Arthritis (JRA) in patients 2 years of age or older ( 1.3 )
1.1Osteoarthritis (OA)
Meloxicam tablets, USP is indicated for relief of the signs and symptoms of osteoarthritis [ see Clinical Studies ( 14.1 ) ].
1.2Rheumatoid Arthritis (RA)
Meloxicam tablets, USP is indicated for relief of the signs and symptoms of rheumatoid arthritis [ see Clinical Studies ( 14.1 ) ].
1.3Juvenile Rheumatoid Arthritis (JRA) Pauciarticular and Polyarticular Course
Meloxicam tablets, USP is indicated for relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients 2 years of age and older [ see Clinical Studies ( 14.2 ) ].
Contraindications
Known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to meloxicam ( 4.1 ) History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs ( 4.1 ) Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery ( 4.2 )
4.1Allergic Reactions
Meloxicam is contraindicated in patients with known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to meloxicam. Meloxicam should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients [ see Warnings and Precautions ( 5.7 , 5.13 ) ].
Meloxicam is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [ see Warnings and Precautions ( 5.1 ) ].
Warnings and precautions
Serious and potentially fatal cardiovascular (CV) thrombotic events, myocardial infarction, and stroke. Patients with known CV disease/risk factors may be at greater risk. ( 5.1 ) Serious gastrointestinal (GI) adverse events which can be fatal. The risk is greater in patients with a prior history of ulcer disease or GI bleeding, and in patients at higher risk for GI events, especially the elderly. ( 5.2 ) Elevated liver enzymes, and rarely, severe hepatic reactions.
Discontinue use immediately if abnormal liver enzymes persist or worsen. ( 5.3 ) New onset or worsening of hypertension. Blood pressure should be monitored closely during treatment. ( 5.4 ) Fluid retention and edema. Should be used with caution in patients with fluid retention or heart failure. ( 5.5 ) Renal papillary necrosis and other renal injury with long-term use. Use with caution in the elderly, those with impaired renal function, heart failure, liver dysfunction, and those taking diuretics, ACE-inhibitors, or angiotensin II antagonists.
The use of meloxicam in patients with severe renal impairment is not recommended. ( 5.6 ) Serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal and can occur without warning. Discontinue meloxicam at first appearance of rash or skin reactions. ( 5.8 )
5.1Cardiovascular 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, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible.
Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [ see Contraindications ( 4.2 ) ].
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 does increase the risk of serious GI events [ see Warnings and Precautions ( 5.2 ) ].
5.2Gastrointestinal (GI)
Effects - Risk of GI Ulceration, Bleeding, and Perforation NSAIDs, including meloxicam, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the 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, occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. Prescribe NSAIDs, including meloxicam, with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding.
Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status.
Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during meloxicam therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected.
This should include discontinuation of meloxicam until a serious GI adverse event is ruled out. For high-risk patients, consider alternate therapies that do not involve NSAIDs.
5.3Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including meloxicam. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported [ see Adverse Reactions ( 6.1 ) ].
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with meloxicam. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue meloxicam [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ].
5.4Hypertension
NSAIDs, including meloxicam, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. NSAIDs, including meloxicam, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
5.5Congestive Heart Failure and Edema
Fluid retention and edema have been observed in some patients taking NSAIDs. Use meloxicam with caution in patients with fluid retention, hypertension, or heart failure.
5.6Renal Effects
Long-term administration of NSAIDs, including meloxicam, can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.
Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. A pharmacokinetic study in patients with mild and moderate renal impairment revealed that no dosage adjustments in these patient populations are required.
Patients with severe renal impairment have not been studied. The use of meloxicam in patients with
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Interactions
See also Clinical Pharmacology ( 12.3 ). Concomitant use of meloxicam and warfarin may result in increased risk of bleeding complications ( 7.7 ) Concomitant use of meloxicam and aspirin is not generally recommended because of the potential of increased adverse effect including increased GI bleeding ( 7.2 ) Concomitant use with meloxicam increases lithium plasma levels ( 7.4 ) Concomitant use with NSAIDs may reduce the antihypertensive effect of ACE-inhibitors ( 7.1 )
7.1ACE-inhibitors
NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking meloxicam concomitantly with ACE-inhibitors.
7.2Aspirin
When meloxicam is administered with aspirin (1000 mg three times daily) to healthy volunteers, an increase the AUC (10%) and C max (24%) of meloxicam was noted. The clinical significance of this interaction is not known; however, as with other NSAIDs concomitant administration of meloxicam and aspirin is not generally recommended because of the potential for increased adverse effects. Concomitant administration of low-dose aspirin with meloxicam may result in an increased rate of GI ulceration or other complications, compared to use of meloxicam alone.
Meloxicam is not a substitute for aspirin for cardiovascular prophylaxis.
7.3Diuretics
Clinical studies, as well as post marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. However, studies with furosemide agents and meloxicam have not demonstrated a reduction in natriuretic effect. Furosemide single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of meloxicam.
Nevertheless, during concomitant therapy with meloxicam, patients should be observed closely for signs of renal failure [ see Warnings and Precautions ( 5.6 ) ], as well as to ensure diuretic efficacy.
7.4 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 every day as compared to subjects receiving lithium alone. These effects have been attributed to inhibition of renal prostaglandin synthesis by meloxicam. Closely monitor patients on lithium treatment for signs of lithium toxicity when meloxicam is introduced, adjusted, or withdrawn.
7.5Methotrexate
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. Therefore, NSAIDs may reduce the elimination of methotrexate, thereby enhancing the toxicity of methotrexate. Use caution when meloxicam is administered concomitantly with methotrexate [ see Clinical Pharmacology ( 12.3 ) ].
7.6Cyclosporine
Meloxicam, like other NSAIDs, may affect renal prostaglandins, thereby altering the renal toxicity of certain drugs. Therefore, concomitant therapy with meloxicam may increase cyclosporine's nephrotoxicity. Use caution when meloxicam is administered concomitantly with cyclosporine.
7.7Warfarin
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. Monitor anticoagulant activity, particularly in the first few days after initiating or changing meloxicam therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding than with the use of either drug alone.
Use caution when administering meloxicam 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 Clinical Pharmacology ( 12.3 ) ].
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Category C; Category
D starting 30 weeks gestation There are no adequate and well-controlled studies in pregnant women. Meloxicam crosses the placental barrier. Prior to 30 weeks gestation, use meloxicam during pregnancy only if the potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, avoid meloxicam and other NSAIDs, in pregnant women as premature closure of the ductus arteriosus in the fetus may occur.
If this drug is used during this time period in pregnancy, inform the patient of the potential hazard to a fetus [ see Warnings and Precautions ( 5.9 ) and Patient Counseling Information ( 17.8 ) ]. Teratogenic Effects 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 maximum recommended human daily dose [MRHD] based on body surface area [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. The no effect level was 20 mg/kg/day (26-fold greater than the MRHD based on BSA conversion). Nonteratogenic Effects 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.
Adverse reactions
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 following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular thrombotic events [ see Boxed Warning and Warnings and Precautions ( 5.1 )] Gastrointestinal effects – risk of GI ulceration, bleeding, and perforation [ see Boxed Warning and Warnings and Precautions ( 5.2 ) ] Hepatic effects [see Warnings and Precautions ( 5.3 )] Hypertension [see Warnings and Precautions ( 5.4 )] Congestive heart failure and edema [see Warnings and Precautions ( 5.5 )] Renal effects [see Warnings and Precautions ( 5.6 )] Anaphylactoid reactions [ see Warnings and Precautions ( 5.7 )] Adverse skin reactions [see Warnings and Precautions ( 5.8 )] Most common (≥5% and greater than placebo) adverse events in adults are diarrhea, upper respiratory tract infections, dyspepsia, and influenza-like symptoms ( 6.1 ) Adverse events observed in pediatric studies were similar in nature to the adult clinical trial experience ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Carlsbad Technology, Inc. at 1-866-431-8284 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch .
6.1Clinical Trials Experience Adults Osteoarthritis and Rheumatoid Arthritis
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 10,500 of these patients were treated in ten placebo- and/or active-controlled osteoarthritis trials and 2363 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 1 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
3.3Skin Rash 2 2.5 2.6 0.6 2.0 1
WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined 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 No. of Patients 469 481 477 Gastrointestinal Disorders 14.1 18.9
16.8 Abdominal Pain NOS 2 0.6 2.9
2.3 Dyspeptic signs and symptoms 1 3.8 5.8
4.0 Nausea 2 2.6 3.3
3.8General Disorders and Administration Site Conditions
Influenza like illness 2 2.1 2.9
2.3Infection and Infestations
Upper respiratory tract infections-pathogen class unspecified 1 4.1 7.0
6.5Musculoskeletal and Connective Tissue Disorders
Joint related signs and symptoms 1 1.9 1.5
2.3 Nervous System Disorders Headaches NOS 2 6.4 6.4
5.5Skin and Subcutaneous Tissue Disorders Rash NOS 2 1.7 1.0 2.1 1
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) 2 MedDRA preferred term: nausea, abdominal pain NOS, influenza-like illness, headaches NOS, and rash NOS 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 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials 4 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 1 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 2 0.3 1.2 3.0
1.3 Urinary Micturition Frequency 0.1 0.4 2.4
1.3Urinary Tract Infection 0.3 0.4 4.7 6.9 1
WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined 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, hyperte
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Composition
Active ingredients
MELOXICAM 7.5MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
