Meloxicam Stella

Meloxicam.

Active ingredient: Meloxicam 7.5 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, povidone K30, croscarmellose sodium, sodium citrate, quinoline yellow, sodium starch glycolate, colloidal anhydrous silica, magnesium stearate.

Short-term symptomatic treatment of exacerbations of osteoarthrosis.
Symptomatic treatment of rheumatoid arthritis or ankylosing spondylitis.

Administration: Meloxicam STELLA Tablets 7.5mg is administered orally. The tablet should be swallowed whole and must not be halved.
Dosage: Meloxicam STELLA Tablets 7.5mg should be used at the lowest effective dose for the shortest possible time.
Exacerbations of osteoarthrosis: 7.5 mg/day (one 7.5 mg tablet); if necessary, in the absence of improvement, the dose may be increased to 15 mg/day (two 7.5 mg tablets).
Rheumatoid arthritis, ankylosing spondylitis: 15 mg/day (two 7.5 mg tablets).
According to the therapeutic response, the dose may be reduced to 7.5 mg/day (one 7.5 mg tablet).
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. The patient's need for symptomatic relief and response to therapy should be reevaluated periodically, especially in patients with osteoarthritis.
DO NOT EXCEED THE DOSE OF 15 MG/DAY.
Special Populations: Elderly patients and patients with increased risks for adverse reaction: The recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg per day. Patients with increased risks for adverse reactions should start treatment with 7.5 mg per day.
Renal impairment: In dialysis patients with severe renal failure, the dose should not exceed 7.5 mg per day. No dose reduction is required in patients with mild to moderate renal impairment (i.e. patients with a creatinine clearance of greater than 25 ml/min).
Hepatic impairment: No dose reduction is required in patients with mild to moderate hepatic impairment.
Children and adolescents: Meloxicam STELLA Tablets 7.5mg is contraindicated in children and adolescents aged under 16 years.

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAID and may occur following an overdose.
Patients should be managed with symptomatic and supportive care following an NSAID overdose. Accelerated removal of meloxicam by 4 g oral doses of cholestyramine given three times a day was demonstrated in a clinical trial.

Meloxicam STELLA Tablets 7.5mg is contraindicated in the following situations: Third trimester of pregnancy; Children and adolescents aged under 16 years; Hypersensitivity to meloxicam or to one of the excipients, or hypersensitivity to substances with a similar action e.g. NSAIDs, aspirin; History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy; Active, or history of recurrent peptic ulcer/haemorrhage; Active intestinal inflammatory disease (Crohn's disease, ulcerative colitis); Severely impaired liver function; Non-dialysed severe renal failure; Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders; Patients with severe heart failure.
Meloxicam should not be given to patients who have developed signs of asthma, nasal polyps, angioneurotic oedema or urticaria following the administration of aspirin or other NSAIDs.
Meloxicam is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
The recommended maximum daily dose should not be exceeded in case of insufficient therapeutic effect, nor should an additional NSAID be added to the therapy because this may increase the toxicity while therapeutic advantage has not been proven. The use of meloxicam with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.
Meloxicam is not appropriate for the treatment of patients requiring relief from acute pain.
In the absence of improvement after several days, the clinical benefit of the treatment should be reassessed.
Any history of oesophagitis, gastritis and/or peptic ulcer must be sought in order to ensure their total cure before starting treatment with meloxicam. Attention should routinely be paid to the possible onset of a recurrence in patients treated with meloxicam and with a past history of this type.
In rare cases, meloxicam has been associated with serious liver injury.
Adverse reactions are often less well tolerated in elderly, fragile or weakened individuals, who therefore require careful monitoring. As with other NSAIDs, particular caution is required in the elderly, in whom renal, hepatic and cardiac functions are frequently impaired. The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Meloxicam, as any other NSAID, may mask symptoms of an underlying infectious disease.
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. In women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.
Gastrointestinal risk: NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events.
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low-dose aspirin, or other drugs likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution is advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as heparin as curative treatment or given in geriatrics, anticoagulants such as warfarin, or other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid given at anti-inflammatory doses (≥1 g as single intake or ≥3 g as total daily amount).
When GI bleeding or ulceration occurs in patients receiving meloxicam, the treatment should be withdrawn.
Cardiovascular and cerebrovascular risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical monitoring of blood pressure for patients at risk is recommended at baseline and especially during treatment initiation with meloxicam.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with meloxicam after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Renal effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis 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, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of meloxicam in patients with advanced renal disease. Therefore, treatment with meloxicam is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable.
Skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk for 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.
Parameters of liver and renal function: As with most NSAIDs, occasional increases in serum transaminase levels, increases in serum bilirubin or other liver function parameters, as well as increases in serum creatinine and blood urea nitrogen as well as other laboratory disturbances, have been reported. The majority of these instances involved transitory and slight abnormalities. Should any such abnormality prove significant or persistent, the administration of meloxicam should be stopped and appropriate investigations undertaken.
Functional renal failure: NSAIDs, by inhibiting the vasodilating effect of renal prostaglandins, may induce a functional renal failure by reduction of glomerular filtration. This adverse event is dose-dependent. At the beginning of the treatment or after dose increase, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors: Elderly; Concomitant treatments such as ACE inhibitors, angiotensin-II antagonists, sartans, diuretics; Hypovolemia (whatever the cause); Congestive heart failure; Renal failure; Nephrotic syndrome; Lupus nephropathy; Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score 10).
In rare instance, NSAIDs may be the cause of interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
The dose of meloxicam in patients with end-stage renal failure on haemodialysis should not be higher than 7.5 mg. No dose reduction is required in patients with mild or moderate renal impairment (i.e. patients with a creatinine clearance of greater than 25 ml/min).
Sodium, potassium and water retention: Induction of sodium, potassium and water retention and interference with the natriuretic effects of diuretics may occur with NSAIDs. Furthermore, a decrease of the antihypertensive effect of antihypertensive drugs can occur. Consequently, oedema, cardiac failure or hypertension may be precipitated or exacerbated in susceptible patients as a result. Clinical monitoring is therefore necessary for patients at risk.
Hyperkalaemia: Hyperkalaemia can be favoured by diabetes or concomitant treatment known to increase kalaemia. Regular monitoring of potassium values should be performed in such cases.
Effects on ability to drive and use machines: There are no specific studies on the ability to drive and use machinery. However, on the basis of the pharmacodynamic profile and reported adverse drug reactions, meloxicam is likely to have no or negligible influence on these abilities. However, when visual disturbances or drowsiness, vertigo or other central nervous system disturbances occur, it is advisable to refrain from driving and operating machinery.

Pregnancy: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for 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 animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, meloxicam should not be given unless clearly necessary. If meloxicam is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); Renal dysfunction, which may progress to renal failure with oligohydroamniosis.
The mother and the neonate, at the end of pregnancy, to: Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; Inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, meloxicam is contraindicated during the third trimester of pregnancy.
Lactation: While no specific experience exists for meloxicam, NSAIDs are known to pass into mother's milk. Administration therefore is not recommended in women who are breastfeeding.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
Oedema, hypertension, and cardiac failure have been reported in association with NSAID treatment.
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed.
The frequencies of adverse drug reactions given as follows are based on corresponding occurrences of reported adverse events in 27 clinical trials with a treatment duration of at least 14 days. The information is based on clinical trials involving 15197 patients who have been treated with daily oral doses of 7.5 or 15 mg meloxicam tablets or capsules over a period of up to one year.
Adverse drug reactions that have come to light as a result of reports received in relation to administration of the marketed product are included.
Adverse reactions have been ranked under headings of frequency using the following convention: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000); not known (cannot be estimated from the available data).
Blood and lymphatic system disorders: Uncommon: Anaemia.
Rare: Blood count abnormal (including differential white cell count), leukopenia, thrombocytopenia.
Very rare cases of agranulocytosis have been reported.
Immune system disorders: Uncommon: Hypersensitivity, allergic reactions other than anaphylactic or anaphylactoid reactions.
Not known: Anaphylactic reaction, anaphylactoid reaction.
Psychiatric disorders: Rare: Mood altered, nightmares.
Not known: Confusional state, disorientation.
Nervous system disorders: Common: Headache.
Uncommon: Dizziness, somnolence.
Eye disorders: Rare: Visual disturbance including vision blurred, conjunctivitis.
Ear and labyrinth disorders: Uncommon: Vertigo.
Rare: Tinnitus.
Cardiac disorders: Rare: Palpitations.
Cardiac failure has been reported in association with NSAID treatment.
Vascular disorders: Uncommon: Blood pressure increased, flushing.
Respiratory, thoracic and mediastinal disorders: Rare: Asthma in individuals allergic to aspirin or other NSAIDs.
Gastrointestinal disorders: Very common: Dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhoea.
Uncommon: Occult or macroscopic gastrointestinal haemorrhage, stomatitis, gastritis, eructation.
Rare: Colitis, gastroduodenal ulcer, oesophagitis.
Very rare: Gastrointestinal perforation.
Not known: Pancreatitis.
Gastrointestinal haemorrhage, ulceration or perforation may sometimes be severe and potentially fatal, especially in elderly.
Hepatobiliary disorders: Uncommon: Liver function disorder (e.g. raised transaminases or bilirubin).
Very rare: Hepatitis.
Skin and subcutaneous tissue disorders: Uncommon: Angioedema, pruritus, rash.
Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.
Very rare: Dermatitis bullous, erythema multiforme.
Not known: Photosensitivity reaction.
Renal and urinary disorders: Uncommon: Sodium and water retention, hyperkalaemia, renal function test abnormal (increased serum creatinine and/or serum urea).
Very rare: Acute renal failure in particular in patients with risk factors.
General disorders and administration site conditions: Uncommon: Oedema including oedema of the lower limbs.
Information characterising individual serious and/or frequently occurring adverse reactions: Very rare cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic drugs.
Adverse reactions which have not been observed yet in relation to the product, but which are generally accepted as being attributable to other compounds in the class: Organic renal injury probably resulting in acute renal failure: Very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported.

Interaction studies have only been performed in adults.
Meloxicam is metabolised in liver, mostly by CYP2C9 and CYP3A4. Possibility of pharmacokinetic interactions between meloxicam and drugs inhibiting or being metabolised by CYP2C9 and CYP3A4 has to be considered.
Pharmacodynamic interactions: Other non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥3 g/d: Combination with other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid given at anti-inflammatory doses (≥1 g as single intake or ≥3 g as total daily amount), is not recommended.
Corticosteroids (e.g. Glucocorticoids): The concomitant use with corticosteroids requests caution because of an increased risk of bleeding or gastrointestinal ulceration.
Anticoagulant or heparin administered in geriatrics or at curative doses: Considerably increased risk of bleeding, via inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants, such as warfarin. The concomitant use of NSAIDs and anticoagulants or heparin administered in geriatrics or at curative dose is not recommended.
In remaining cases of heparin use, caution is necessary due to an increased bleeding risk. Careful monitoring of the INR is required if it proves impossible to avoid such combination.
Thrombolytics and antiplatelet drugs: Increased risk of bleeding, via inhibition of platelet function and damage to the gastroduodenal mucosa.
Selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors and Angiotensin-II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of an ACE inhibitor or angiotensin-II antagonists and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Other antihypertensive drugs (e.g. Beta-blockers): As for the latter, a decrease of the antihypertensive effect of beta-blockers (due to inhibition of prostaglandins with vasodilatory effect) can occur.
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus): Nephrotoxicity of calcineurin inhibitors may be enhanced by NSAIDs via renal prostaglandin-mediated effects. During combined treatment, renal function is to be measured. A careful monitoring of the renal function is recommended, especially in the elderly.
Intrauterine devices: NSAIDs have been reported to decrease the efficacy of intrauterine devices.
A decrease of the efficacy of intrauterine devices by NSAIDs has been previously reported but needs further confirmation.
Pharmacokinetic interactions: Effect of meloxicam on the pharmacokinetics of other drugs: Lithium: NSAIDs have been reported to increase blood lithium 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.
Methotrexate: 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 NSAID preparations 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 the 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 relevantly affected by concomitant meloxicam treatment, it should be considered that the haematological toxicity of methotrexate can be amplified by treatment with NSAID drugs.
Effect of other drugs on the pharmacokinetics of meloxicam: No clinically relevant pharmacokinetic drug-drug interactions were detected with respect to the concomitant administration of antacids, cimetidine and digoxin.
Cholestyramine: Cholestyramine accelerates the elimination of meloxicam by interrupting the enterohepatic circulation so that clearance for meloxicam increases by 50% and the half-life decreases to 13+3 hrs. This interaction is of clinical significance.

Store in a well-closed container, in a dry place. Protect from moisture. Do not store above 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AC06 - meloxicam ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, oxicams.

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