Advertisement

Topics

These highlights do not include all the information needed to use meloxicam tablets safety and effectively. See full prescribing information for meloxicam tablets Initial U.S. Approval: 2000 | meloxicam

14:00 EDT 24th July 2014 | BioPortfolio
Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

WARNING: RISK OF SERIOUS CARDIOVASCULAR and GASTROINTESTINAL EVENTS

Cardiovascular Risk

Gastrointestinal Risk

Meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [see CLINICAL STUDIES (14.1)].

Meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [see CLINICAL STUDIES (14.1)].

Carefully consider the potential benefits and risks of meloxicam tablets and other treatment options before deciding to use meloxicam tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS (5.4)].

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 are 15 mg regardless of formulation. In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended [see WARNINGS AND PRECAUTIONS (5.6), USE IN SPECIFIC POPULATIONS (8.7) AND CLINICAL PHARMACOLOGY (12.3)].

Meloxicam 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.

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.

Tablets:

Meloxicam Tablets are contraindicated in patients with known hypersensitivity (e.g. anaphylactoid reactions and serious skin reactions) to meloxicam. Meloxicam tablets 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 tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see WARNINGS AND PRECAUTIONS (5.1)].

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 10-14 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)].

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 3-6 months, and in about 2-4% 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.

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)].

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.

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.

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 severe renal impairment with CrCl less than 20 mL/min is not recommended. A study performed in patients on hemodialysis revealed that although overall C was diminished in this population, the proportion of free drug not bound to plasma was increased. Therefore it is recommended that meloxicam dosage in this population not exceed 7.5 mg per day. Closely monitor the renal function of patients with impaired renal function who are taking meloxicam [see DOSAGE AND ADMINISTRATION (2.1), USE IN SPECIFIC POPULATIONS (8.7) AND CLINICAL PHARMACOLOGY (12.3)].

Use caution when initiating treatment with meloxicam in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with meloxicam. Caution is also recommended in patients with pre-existing kidney disease.

The extent to which metabolites may accumulate in patients with renal impairment has not been studied with meloxicam. Because some meloxicam metabolites are excreted by the kidney, monitor patients with significant renal impairment closely.

As with other NSAIDs, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam. Meloxicam should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs [see CONTRAINDICATIONS (4.1) AND WARNINGS AND PRECAUTIONS (5.12)]. Seek emergency help in cases where an anaphylactoid reaction occurs.

NSAIDs, including meloxicam, can cause serious skin adverse events 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 manifestations and discontinue use of the drug at the first appearance of skin rash or any other sign of hypersensitivity.

Starting at 30 weeks gestation, avoid the use of meloxicam, because it may cause premature closure of the ductus arteriosus [see USE IN SPECIFIC POPULATIONS (8.1) AND PATIENT COUNSELING INFORMATION (17.8)].

Meloxicam cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Slowly taper patients on prolonged corticosteroid therapy if a decision is made to discontinue corticosteroids.

The pharmacological activity of meloxicam in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

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

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Carefully monitor patients treated with meloxicam who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, meloxicam should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, meloxicam should be discontinued.

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:

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, 3,505 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.

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

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.

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

Table 1aAdverse 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
1WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined
2WHO preferred terms rash, rash erythematous and rash maculo-papular combined
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
      Edema1
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





     Rash2

2.5

2.6

0.6

2.0
Table 1bAdverse 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
1MedDRA 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)
2MedDRA preferred term: nausea, abdominal pain NOS, influenza-like illness, headaches NOS, and rash NOS
No .  of  Patients
469
481
477
Gastrointestinal  disorders
14.1
18.9
16.8
Abdominal pain NOS2
0.6
2.9
2.3
Dyspeptic signs and symptoms1
3.8
5.8
4.0
Nausea2
2.6
3.3
3.8
General  disorders  and  administration  site  conditions



Influenza like illness2
2.1
2.9
2.3
Infection  and  infestations



Upper respiratory tract infections-pathogen class unspecified1
4.1
7.0
6.5
     Musculoskeletal  and  connective  tissue   disorders



Joint related signs and symptoms 1
1.9
1.5
2.3
      Nervous  system  disorders



Headaches NOS2
6.4
6.4
5.5
Skin  and  subcutaneous  tissue  disorders



Rash NOS2
1.7
1.0
2.1
Table 2Adverse Events (%) Occurring in ≥ 2% of Meloxicam Patients in 4 to 6 Weeksand 6 Month Active-Controlled Osteoarthritis Trials

4 - 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.

Manufacturer

MedVantx, Inc.

Active Ingredients

Source

Drugs and Medications [41 Associated Drugs and Medications listed on BioPortfolio]

Meloxicam [Aurobindo Pharma Limited]

These highlights do not include all the information needed to use meloxicam safely and effectively.  See full prescribing information for meloxicam tablets.Meloxicam Tablets, USP  Initial U.S. Appr...

Meloxicam [PD-Rx Pharmaceuticals, Inc.]

These highlights do not include all the information needed to use Meloxicam Tablets USP safely and effectively. See full prescribing information for Meloxicam Tablets USP Meloxicam Tablets USP Initial...

Meloxicam [Unichem Pharmaceuticals (USA), Inc.]

These highlights do not include all the information needed to use Meloxicam Tablets USP safely and effectively. See full prescribing information for Meloxicam Tablets USP Meloxicam Tablets USP Initial...

Meloxicam [Unit Dose Services]

These highlights do not include all the information needed to use Meloxicam Tablets USP safely and effectively. See full prescribing information for Meloxicam Tablets USP Meloxicam Tablets USP Initial...

Meloxicam [Bryant Ranch Prepack]

These highlights do not include all the information needed to use Meloxicam Tablets USP safely and effectively. See full prescribing information for Meloxicam Tablets USP Meloxicam Tablets USP Initial...

Clinical Trials [13 Associated Clinical Trials listed on BioPortfolio]

Bioequivalence Study of Meloxicam Tablets 15 mg of Dr.Reddy's Laboratories Limited Under Fed Condition

The objective of this study is to determine the relative bioavailability of one 15 mg Meloxicam tablet (Dr. Reddy. Laboratories Ltd.,Generics) versus one 15 mg Mobic (meloxicam) Tablet (Bo...

Meloxicam SoluMatrix® Capsules vs Meloxicam Tablets to Treat Osteoarthritis Pain

The purpose of this study is to evaluate the safety and efficacy of a low dose and a high dose of Meloxicam SoluMatrix® Capsules versus Meloxicam Tablets for the treatment of pain due to...

Bioequivalence Study of Meloxicam Tablets 15 mg of Dr.Reddy's Laboratories Limited Under Fasting Condition

The objective of this study is to determine the relative bioavailability of one 15 mg Meloxicam tablet (Dr. Reddy. Laboratories Ltd.,Generics) versus one 15 mg Mobic (meloxicam) Tablet (Bo...

Bioequivalency Study of Meloxicam Tablets Under Fasting Conditions

The objective of this study was the bioequivalence of a Roxane Laboratories' Meloxicam tablets, 15 mg, to Mobic® Tablets, 15 mg (Boehringer Ingelheim) under fasting conditions using a sin...

A Multi-Center Trial to Compare Three Doses of Meloxicam and Placebo in Patients With Rheumatoid Arthritis

A 12-week trial consisting of 5 visits (6 if follow up is needed) to find out how effective and safe three different doses of meloxicam are compared with placebo in Rheumatoid Arthritis. P...

PubMed Articles [18 Associated PubMed Articles listed on BioPortfolio]

Polymeric nanocapsules as a technological alternative to reduce the toxicity caused by meloxicam in mice.

This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocap...

Pharmacokinetic profiles of meloxicam in turtles (Trachemys scripta scripta) after single oral, intracoelomic and intramuscular administrations.

Meloxicam is an anti-inflammatory and analgesic drug used to treat many pathological conditions in turtles. With the aim to fill the lack of data about its pharmacokinetic in this species, eighteen tu...

Subcutaneous meloxicam suspension pharmacokinetics in mice and dose considerations for postoperative analgesia.

Meloxicam is a cyclooxygenase (COX) inhibitor with a higher selectivity for cyclooxygenase-2 (COX-2) than for cyclooxygenase-1 (COX-1). In the laboratory setting, this nonsteroidal anti-inflammatory d...

Experimental study on the effect of oral meloxicam administration in sows on pre-weaning mortality and growth and immunoglobulin G transfer to piglets.

Parturation is an intrinsically risky and painful process for both the sow and the piglets that can cause welfare and economic problems. Non-steroidal anti-inflammatory drugs (NSAIDs) have been demons...

Evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis.

The aim of the study was to investigate the effect of the non-steroidal anti-inflammatory drug meloxicam on the clinical course of obstructive idiopathic cystitis in cats in a placebo-controlled clini...

Quick Search
Advertisement
 

Relevant Topics

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...


Drugs and Medication Quicklinks


Searches Linking to this Drug Record