Revision Year: 2022 Publisher: Alphapharm Pty Ltd trading as Viatris, Level 1, 30 The Bond, 30-34 Hickson Road, Millers Point NSW 2000 www.viatris.com.au Phone: 1800 274 276
As with all NSAIDs, MOXICAM is contraindicated in patients with recent cerebrovascular bleeding or established systemic bleeding disorders.
As with other NSAIDs, gastrointestinal (GI) bleeding, ulceration or perforation, potentially fatal, can occur at any time during treatment, with or without warning symptoms or a previous history of serious GI events. The consequences of such events are generally more serious in the elderly. Minor upper GI problems, such as dyspepsia, are common and may occur at any time during NSAID therapy. Therefore, doctors and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for three to six months, and in about 2 to 4% of patients treated for one year. These trends continue, increasing the likelihood of developing a serious adverse GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
Studies have shown that patients with a prior history of ulcer disease and/or gastrointestinal bleeding and who use NSAIDs have a greater than 10-fold higher risk of developing a GI bleed than patients with neither of these factors.
Caution is advised in patients most at risk of developing a GI complication with NSAIDs: the elderly, patients using any other NSAID or aspirin concomitantly or patients with a prior history of or recent GI disease such as ulceration and GI bleeding.
NSAIDs should be prescribed with caution in patients with a prior history of or recent ulcer disease or GI bleeding.
For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
In clinical trials, meloxicam has been shown to cause fewer GI adverse events (including dyspepsia, abdominal pain, nausea, vomiting, etc.) than other NSAIDs with which it has been compared (see Table 1).
Table 1. Incidence of GI Adverse Events (%) after 4 weeks, 12 weeks and 6 months:
| 4-week Treatment | 12-week Treatment | 6-month Treatment | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MELISSA/SELECT | Placebo-controlled trial | Active-controlled trial | ||||||||
| melox. 7.5 mg | diclo. (SR) 100 mg | pirox. 20 mg | melox. 7.5 mg | melox. 15 mg | placebo | diclo. BID (2x 50 mg) | melox. 7.5 mg | melox. 15 mg | diclo. 100 mg | pirox. 20 mg |
| n=8955 | n=4688 | n=4336 | n=154 | n=156 | n=157 | n=153 | n=169 | n=306 | n=167 | n=149 |
| 12% | 19% | 15% | 20% | 17% | 17% | 28% | 27% | 24% | 28% | 30% |
KEY: melox. = meloxicam; pirox. = piroxicam; diclo. = diclofenac; SR = slow release; BID = twice daily
Caution should be exercised when treating patients with a history of upper gastrointestinal disease and in patients receiving treatment with anticoagulants. Patients with GI symptoms should be monitored. Meloxicam therapy should cease if peptic ulceration or GI ulceration or bleeding occurs.
Co-administration of meloxicam with drugs known to inhibit CYP 3A4 should be undertaken with caution. A combination of meloxicam and substances known to inhibit both CYP 3A4 and CYP 2C9 should be avoided because of the increased risk of toxicity.
Long term therapy with some COX-2 selective NSAIDs of the coxib class has been shown to increase the risk of serious cardiovascular thrombotic events. Meloxicam is a COX-2 selective NSAID. Meloxicam has not been demonstrated to increase the risk of cardiovascular adverse events compared to nonselective NSAIDs in clinical trials. However, long term placebo-controlled data to adequately assess any cardiovascular risk are not available for Meloxicam.
All NSAIDs, both COX-2 selective and nonselective, may cause an increased risk of serious cardiovascular thrombotic events including myocardial infarction and stroke. This may increase with dose and duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. To minimise the potential risk of an adverse cardiovascular event in patients taking meloxicam especially in those with cardiovascular risk factors the lowest effective dose should be used for the shortest possible duration.
Physicians and patients should remain alert for such cardiovascular events even in the absence of previous cardiovascular symptoms. Patients should be informed about signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, and Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS) (see subheading below) have been reported very rarely in association with the use of meloxicam. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Meloxicam should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
DRESS has been reported in patients taking NSAIDs. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.
The use of an ACE inhibiting drug (ACE-inhibitor or angiotensin receptor antagonist), an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.
Induction of sodium, potassium and water retention and interference with the natriuretic effects of diuretics may occur with NSAIDs. Cardiac failure or hypertension may be precipitated or exacerbated in susceptible patients as a result. For patients at risk, clinical monitoring is recommended.
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.
Meloxicam cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of meloxicam in reducing inflammation and possibly fever may diminish the utility of these diagnostic signs in detecting complications of presumed non-infectious, painful conditions.
As with other NSAIDs, anaphylactoid reactions may occur 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. Emergency help should be sought in cases where an anaphylactoid reaction occurs.
MOXICAM tablets 7.5 mg contain 43 mg lactose monohydrate and MOXICAM tablets 15 mg contain 86 mg lactose monohydrate per maximum recommended daily dose. Patients with rare hereditary problems of galactose intolerance, e.g. galactosaemia, should not take this medicine.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including meloxicam. These laboratory values 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 with NSAIDs.
Physicians and patients should remain alert for hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity. Patients with signs and/or symptoms suggesting liver dysfunction (e.g., nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and “flu-like” symptoms), 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), meloxicam should be discontinued.
NSAIDs inhibit the synthesis of renal prostaglandins, which play a supportive role in the maintenance of renal perfusion. In patients whose renal blood flow and blood volume are decreased, administration of an NSAID may precipitate overt renal decompensation which is typically followed by recovery to pre-treatment state upon discontinuation of nonsteroidal anti-inflammatory therapy.
Patients at greatest risk of such a reaction are elderly individuals, dehydrated patients, those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease, those receiving concomitant treatment with a diuretic, ACE inhibitor or angiotensin II receptor antagonist or those having undergone major surgical procedures which led to hypovolaemia. In such patients, the renal function, including volume of diuresis, should be carefully monitored at the beginning of therapy.
In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
The dose of meloxicam in patients with end-stage renal failure on haemodialysis should not exceed 7.5 mg. No dose reduction is required in patients with mild or moderate renal impairment (i.e., in patients with a creatinine clearance of greater than 25 mL/min).
The extent to which metabolites of meloxicam may accumulate in patients with renal failure has not been studied. As some metabolites are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.
Frail or debilitated patients may tolerate side effects less well and such patients should be carefully supervised. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic, or cardiac function.
Meloxicam is not recommended for use in children and adolescents under 18 years of age (see Section 4.3 CONTRAINDICATIONS).
No data available.
In vitro drug interaction studies revealed that the metabolism of meloxicam is predominantly mediated via the CYP 2C9 isoenzyme, with a minor contribution of the CYP 3A4 isoenzyme in the liver. Co-administration of meloxicam with drugs known to inhibit CYP 2C9 is contraindicated. Co-administration of meloxicam with drugs known to inhibit CYP 3A4 (ketoconazole, itraconazole, erythromycin) or drugs known to be metabolised by CYP 3A4 (terfenadine, astemizole, ciclosporin, class III antiarrhythmic drugs such as amiodarone and quinidine) should be undertaken with caution (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE – Gastrointestinal Effects).
No pharmacokinetic interaction was detected with concomitant administration of antacids.
Concomitant administration of 200 mg cimetidine QID 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 betaacetyldigoxin administration for 7 days at clinical doses. In vitro testing found no protein binding drug interaction between digoxin and meloxicam.
Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide (frusemide) and thiazide diuretics in some patients. This effect has been attributed to inhibition of renal prostaglandin synthesis. Studies with furosemide (frusemide) agents and meloxicam have not demonstrated a reduction in natriuretic effect. Furosemide (frusemide) single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of meloxicam. Nevertheless, during concomitant therapy with furosemide (frusemide) and meloxicam, patients should be observed closely for signs of declining renal function (see Section 4.5 INTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS – Diuretics), as well as to assure diuretic efficacy.
Co-administration of meloxicam with drugs known to inhibit CYP 2C9 is contraindicated. Co-administration of meloxicam with drugs known to inhibit CYP 3A4 should be undertaken with caution (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE – Gastrointestinal Effects).
Co-administration of PSIs may increase the risk of gastrointestinal ulcers and bleeding, via a synergistic effect, and is not recommended. The concomitant use of meloxicam with other NSAIDs is not recommended.
There is an increased risk of bleeding via inhibition of platelet function, when NSAIDs are co-administered. If such co-prescribing cannot be avoided, close monitoring of their effects on coagulation is required.
NSAIDs have been reported to increase lithium plasma levels (via decreased renal excretion of lithium), which may reach toxic values. The concomitant use of lithium and NSAIDs is not recommended. If this combination appears necessary, lithium plasma concentrations should be monitored carefully during the initiation, adjustment and withdrawal of meloxicam treatment.
Meloxicam did not have a significant effect on the pharmacokinetics of single doses of methotrexate. In vitro, methotrexate did not displace meloxicam from human serum binding sites. However, as with other NSAIDs, meloxicam may increase the haematologic toxicity of methotrexate. In this situation, strict monitoring of blood cell count is recommended.
NSAIDs can reduce the tubular secretion of methotrexate thereby increasing the plasma concentrations of methotrexate. For this reason, for patients on high dosages of methotrexate (more than 15 mg/week) the concomitant use of NSAIDs is not recommended. The risk of an interaction between NSAIDs and methotrexate should be considered also in patients on low dosage of methotrexate, especially in patients with impaired renal function. In case combination treatment is necessary, blood cell count and renal function should be monitored. Caution should be taken in case both NSAID and methotrexate are given within 3 days, in which case the plasma level of methotrexate may increase and cause increased toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, it should be considered that the haematological toxicity of methotrexate can be amplified by treatment with NSAIDs.
For the concomitant use of meloxicam with pemetrexed in patients with creatinine clearance from 45 to 79 mL/min, the administration of meloxicam should be paused for 5 days before, on the day of, and 2 days following pemetrexed administration. If a combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastro-intestinal adverse reactions. In patients with creatinine clearance below 45 mL/min the concomitant administration of meloxicam with pemetrexed is not recommended.
NSAIDs have been reported to decrease the efficacy of intrauterine devices.
Treatment with NSAIDs is associated with the potential for acute renal insufficiency in patients who are dehydrated. Patients receiving meloxicam and diuretics should be adequately hydrated and be monitored for renal function prior to initiating treatment.
Nephrotoxicity of ciclosporin may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combined treatment, renal function is to be measured.
A reduced effect of the antihypertensive drug by inhibition of vasodilating prostaglandins has been reported during treatment with NSAIDs.
NSAIDs and angiotensin-II receptor antagonists as well as ACE inhibitors exert a synergistic effect on the decrease of glomerular filtration. In patients with pre-existing renal impairment this may lead to acute renal failure.
Colestyramine binds to meloxicam in the gastrointestinal tract leading to a faster elimination of meloxicam.
Interactions via CYP 2C9 can be expected in combination with medicinal products such as oral anti-diabetics (sulfonylureas), which may lead to increased plasma levels of these drugs and meloxicam. Patients concomitantly using meloxicam with sulfonylureas should be carefully monitored for hypoglycaemia.
Oral treatment with meloxicam at doses up to 5 mg/kg/day in female rats (approximately 2.7 times the human dose based on BSA) and up to 9 mg/kg/day (approximately 5 times the human dose based on BSA) in male rats did not affect mating behaviour or fertility.
Oral treatment of female rats with meloxicam at doses of 1 mg/kg/day (approximately half of the human dose based on BSA) reduced the number of embryonic implantations and increased the number of early resorptions. A no-effect dose for these effects was not established. A reduction in the number of corpora lutea was also observed at 5 mg/kg/day, with the no-effect dose being 2.5 mg/kg/day (approximately 1.5-fold greater than the human dose based on BSA).
The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Meloxicam may delay ovulation. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.
Meloxicam use is not recommended in pregnancy (see Section 4.3 CONTRAINDICATIONS).
Inhibition of prostaglandin-synthesis may adversely affect pregnancy and/or the embryofetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy.
The absolute risk of cardiovascular malformation was increased from less than 1% up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In preclinical studies, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryofetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis period.
From about 20 weeks of pregnancy all prostaglandin-synthesis inhibitors may expose the fetus to:
During the third trimester of pregnancy all prostaglandin-synthesis inhibitors may expose the fetus to:
The mother and the neonate, at the end of pregnancy, to:
Meloxicam was not teratogenic in rats up to an oral dose of 4 mg/kg/day (approximately 2.2 times the human dose at 15 mg/day for a 50 kg adult based on body-surface-area (BSA)) when given during organogenesis. Meloxicam caused an increased incidence of septal defect of the heart, a rare event, at an oral dose of 60 mg/kg/day (about 60 times the human dose based on BSA) and embryolethality at oral doses ≥5 mg/kg/day (5 times the human dose based on BSA) when rabbits were treated throughout organogenesis.
Studies in rats with meloxicam, as with other drugs known to inhibit prostaglandin synthesis, showed an increased incidence of still births, increased length of delivery time and delayed parturition at oral doses ≥1 mg/kg/day (approximately 0.6 times the human dose based on BSA), and decreased pup survival at an oral dose of 4 mg/kg/day (approximately 2.1 times the human dose based on BSA) throughout organogenesis. Similar findings were observed in rats receiving oral doses ≥0.125 mg/kg/day (less than 0.1 times the human dose based on BSA) during late gestation and the lactation period.
Meloxicam crosses the placental barrier. There are no adequate, well-controlled studies in pregnant women.
Use of NSAIDs from about 20 weeks gestation may cause 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. Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
Studies of meloxicam excretion in human milk have not been conducted. However, meloxicam was excreted in the milk of lactating rats at concentrations higher than those in plasma. The safety of meloxicam in humans during lactation has not been established and therefore, the drug should not be used during lactation.
There are no specific studies about effects on the ability to drive vehicles and to use machinery. Patients who experience visual disturbances, drowsiness or other central nervous system disturbances should refrain from these activities.
The meloxicam phase II/III safety database includes 10,122 osteoarthritis patients and 1,012 rheumatoid arthritis patients treated with meloxicam 7.5 mg/day and 3,505 osteoarthritis patients and 1,351 rheumatoid arthritis patients treated with meloxicam 15 mg/day. Meloxicam at these doses was administered to 661 patients for at least six 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 2,362 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, multicentre, double-blind, randomised 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. Table 2 presents the adverse events that occurred in greater than or equal to 1% of the meloxicam treatment groups.
Table 2. Adverse Events (%) Occurring in ≥1% of Meloxicam Patients in a 12-week Osteoarthritis Placebo- and Active-controlled Trial:
| Placebo | Meloxicam 7.5 mg daily | Meloxicam 15 mg daily | Diclofenac 10 mg daily | |
|---|---|---|---|---|
| No. of patients | 157 | 154 | 156 | 153 |
| Ear and labyrinth disorders | ||||
| Ear disorder Vertigo | 0 0 | 0 0.6 | 1.3 1.3 | 0.7 0.7 |
| Eye disorders | ||||
| Cataract | 0 | 0 | 1.3 | 1.3 |
| Gastrointestinal | ||||
| Abdominal pain Constipation Diarrhoea Dyspepsia Eructation Flatulence Gastro-oesophageal reflux disease Nausea Vomiting | 2.5 1.9 3.8 4.5 0 4.5 0 3.2 1.9 | 1.9 1.9 7.8 4.5 0 3.2 0.6 3.9 1.3 | 2.6 0.6 3.2 4.5 1.3 3.2 1.9 3.8 1.3 | 1.3 3.9 9.2 6.5 0 3.9 1.3 7.2 2.6 |
| General disorders and administration site conditions | ||||
| Fatigue Gravitational oedema Influenza like illness Oedema peripheral | 1.9 0.6 5.1 1.3 | 1.9 1.3 4.5 0.6 | 1.3 1.9 5.8 3.2 | 1.3 3.3 2.6 0 |
| Immune system disorders | ||||
| Hypersensitivity | 1.9 | 1.9 | 0.6 | 1.3 |
| Infections and infestations | ||||
| Pharyngitis Sinusitis Upper respiratory tract infection | 1.3 5.1 1.9 | 0.6 1.3 3.2 | 3.2 1.9 1.9 | 1.3 5.9 5.9 |
| Injury, poisoning and procedural complications | ||||
| Accident at home Fall | 1.9 0.6 | 4.5 2.6 | 3.2 0 | 2.6 1.3 |
| Metabolism and nutrition disorders | ||||
| Dehydration Increased appetite | 0 0.6 | 1.3 0 | 0 1.3 | 0 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia Arthritis Back pain Bursitis Muscle spasms Myalgia Pain in extremity | 1.9 0 3.2 0.6 1.3 0 0 | 1.9 0 1.3 1.9 1.3 1.3 1.3 | 1.3 1.9 1.9 1.3 1.9 1.3 0.6 | 1.3 0 2.0 0 1.3 0 0.7 |
| Nervous system disorders | ||||
| Carpal tunnel syndrome Dizziness Headache | 0 3.2 10.2 | 1.3 2.6 7.8 | 0.6 3.8 8.3 | 1.3 2.0 5.9 |
| Psychiatric disorders | ||||
| Insomnia | 0.6 | 0 | 1.9 | 2.0 |
| Renal and urinary disorders | ||||
| Haematuria | 0.6 | 0 | 1.3 | 0.7 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough Dyspnoea Pleuritic pain | 0.6 0 0 | 1.3 0 0 | 0.6 1.3 1.3 | 1.3 .7 0 |
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis Pruritus Purpura Rash | 0 0.6 1.3 1.9 | 0 1.3 1.9 1.9 | 1.3 0.6 0 0 | 0 0 0.7 0.7 |
| Vascular disorders | ||||
| Hypertension | 2.5 | 0.6 | 1.9 | 0 |
Adverse events that occurred in ≥1% of the meloxicam treatment groups in two 12-week placebo-controlled rheumatoid arthritis trials are presented in Table 3.
Table 3. Adverse Events (%) Occurring in ≥1% of Meloxicam Patients in Two 12-week Rheumatoid Arthritis Placebo-controlled Trials:
| Placebo | Meloxicam 7.5 mg daily | Meloxicam 15 mg daily | Diclofenac 10 mg daily | |
|---|---|---|---|---|
| No. of patients | 470 | 482 | 478 | 182 |
| Gastrointestinal | ||||
| Abdominal pain Abdominal pain upper Constipation Diarrhoea Dyspepsia Flatulence Nausea Vomiting | 0.6 0.9 0.9 5.3 3.6 1.1 2.6 2.3 | 3.1 1.9 1.5 5.2 5.6 1.2 3.3 0.8 | 2.3 1.0 1.7 3.3 3.6 1.5 3.8 1.3 | 4.4 0 3.8 6.0 7.1 5.5 7.7 1.1 |
| General disorders and administration site conditions | ||||
| Influenza like illness | 2.1 | 2.3 | 2.3 | 5.5 |
| Immune system disorders | ||||
| Hypersensitivity | 0.4 | 1.2 | 0.2 | 0 |
| Infections and infestations | ||||
| Bronchitis Nasopharyngitis Pharyngitis Rhinitis Sinusitis Upper respiratory tract infection Urinary tract infection | 0.2 0.6 0.6 0.4 1.3 2.1 1.3 | 0.6 1.7 0.8 0.6 1.7 4.1 1.2 | 1.3 1.9 1.0 1.0 1.5 4.0 1.3 | 0.5 0 1.1 1.1 1.6 2.7 1.6 |
| Injury, poisoning and procedural complications | ||||
| Fall | 0.2 | 0.6 | 1.0 | 0.5 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia Back pain Myalgia Rheumatoid arthritis | 1.9 2.3 0.2 2.3 | 1.0 1.5 1.0 1.9 | 1.7 1.9 0.6 1.5 | 2.2 2.2 0.5 1.6 |
| Nervous system disorders | ||||
| Dizziness Headache | 3.0 6.6 | 2.3 6.6 | 0.6 5.4 | 3.3 9.3 |
| Psychiatric disorders | ||||
| Insomnia | 0.6 | 1.0 | 0.6 | 1.1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1.5 | 0.8 | 1.5 | 2.2 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus Purpura Rash | 1.3 0.2 1.7 | 0.6 0.2 1.0 | 1.0 1.0 2.3 | 1.1 0 3.8 |
| Vascular disorders | ||||
| Hypertension | 0.9 | 1.5 | 1.0 | 2.2 |
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 events occurring in <1% of patients, which may be causally related to the administration of meloxicam. The information is based on clinical trials involving patients who have been treated with daily oral doses of 7.5 or 15 mg meloxicam tablets over a period of up to 18 months (mean duration of treatment 127 days).
Blood and lymphatic system disorders: Blood count abnormal (including differential white cell count), leukopenia, thrombocytopenia, anaemia.
Concomitant administration of a potentially myelotoxic drug, in particular methotrexate, appears to be a predisposing factor to the onset of a cytopenia.
Cardiac disorders: Palpitations.
Ear and labyrinth disorders: Tinnitus.
Gastro-intestinal disorders: Gastro-intestinal perforation, occult or macroscopic gastro-intestinal haemorrhage, gastroduodenal ulcer, colitis, oesophagitis, stomatitis.
Gastro-intestinal haemorrhage, ulceration or perforation may potentially be fatal.
Hepatobiliary disorders: Transitory abnormalities of liver function parameters (e.g. raised transaminases or bilirubin).
Nervous system disorders: Somnolence.
Renal and urinary disorders: Renal function test abnormal (increased serum creatinine and/or serum urea).
Respiratory, thoracic and mediastinal disorders: Onset of asthma attacks in individuals allergic to aspirin or other NSAIDs.
Skin and subcutaneous tissue disorders: Urticaria, photosensitivity reaction
Vascular disorders: Flushing.
Additional reports of adverse events which may be causally associated to the administration of meloxicam during worldwide post-marketing experience are included below.
General disorders and administration site conditions: In rare cases, other drugs of this class are reported to cause meningitis.
Eye disorders: Visual disturbance including blurred vision, conjunctivitis
Gastrointestinal disorders: Gastritis
Hepatobiliary disorders: Hepatitis
Immune system disorders: Anaphylactic reaction, anaphylactoid reaction and other immediate hypersensitivity.
Psychiatric disorders: Confusional state, disorientation, mood altered
Renal and urinary disorders: Acute renal failure. The use of NSAIDs may be related to micturition disorders, including acute urinary retention.
Reproductive system and breast disorders: Infertility female, ovulation delayed.
Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, dermatitis bullous, erythema multiforme.
Additional adverse events, reported from clinical trials or from spontaneous reports, where evidence for a causal association with meloxicam use is unclear, are the following: cardiac failure, angina, myocardial infarction, arrhythmia, vasculitis, agranulocytosis, interstitial nephritis, convulsion, liver failure.
The following serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for meloxicam. These include oligohydramnios and neonatal renal impairment.
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
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