Avegesic Tablet 7.5mg: Meloxicam 7.5 mg/tablet.
Avegesic Tablet 15mg: Meloxisam 15 mg/tablet.
Pharmacology: Pharmacodynamics: Non-steroidal anti-inflammatory agent (M; locomotor system).
Meloxicam is a non- steroidal anti- inflammatory drug (NSAID) of the oxicam family, with antiinflammatory, analgesic and antipyretic properties. The anti- inflammatory activity of meloxicam has been proven in classical models of inflammation. As with other NSAIDs, its precise mechanism of action remains unknown. However there is at least one common mode of action shared by all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, known inflammation mediators.
Pharmacokinetics: The bioavailability of meloxicam following oral administration is on the average 89%.
With the doses of 7.5 and 15 mg, plasma concentrations are proportional to dose: 0.4 to 1.0 mg/lt for 7.5 mg and 0.8 to 2.0 mg/lt for 15 mg, on average (Cmin and Cmax at steady state).
Meloxicam is very strongly bound to plasma proteins, essentially albumin (99%).
Meloxicam is extensively metabolized, chiefly by oxidation of the methyl radical attached to the thiazolyl ring. Elimination is unchanged form accounts for 3% of the dose. Half of the substance is eliminated in urine and the other half in faeces.
The mean elimination half-life of the order of 20 hours.
Steady state is reached in 5 days.
In terminal renal failure, the volume of distribution is increased and a daily dose of 7.5 mg must not be exceeded.
Plasma clearance is on average 8 ml/min. Clearance is decreased in the elderly. Volume of distribution is low, on average 11 litres. Inter individual variation is the order of 30 - 40%.
Symptomatic treatment of painful osteoarthritis (arthrosis, degenerative joint disease).
Symptomatic treatment of rheumatoid arthritis. Symptomatic treatment of ankylosing spondylitis.
Meloxicam may be taken without regard to timing of meals.
Osteoarthritis: 7.5mg per day. If necessary, the dose may be increased to 15 mg/day.
Rheumatoid arthritis: 15 mg/day. According to therapeutic response, the dose may be reduced to 7.5 mg/day.
Ankylosing spondylitis: 15 mg/day.
In patients with increased risks of adverse reactions: Start treatment at the dose of 7.5 mg/day.
In dialysis patients with severe renal failure: The dose should not exceed 7.5 mg/day.
The total daily dosage of meloxicam should not exceed 15mg. As a dosage for used in children has yet to established, usage should be restricted to adults. Tablets should be swallowed with water or other fluid in conjunction with food.
Elderly: In elderly patients being treated for rheumatoid arthritis the recommended dose for long term treatment is 7.5 mg a day.
Children (Under 15years of age): Not recommended After assessing the risk/ benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used.
Mode of administration: Oral administration.
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 NSAIDs and may occur following an overdose. In case of overdosage, patients should be managed with symptomatic and supportive care. In cases of acute overdose, gastric lavage followed by activated charcoal is recommended. For substantial overdose or severely symptomatic patients, activated charcoal may be administered repeatedly. Administration of cholestyramine may be useful following an overdose.depression, coma, convulsions, cardiovascular collapse and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs and may occur following an overdose.
In case of overdosage, patients should be managed with symptomatic and supportive care. In cases of acute overdose, gastric lavage followed by activated charcoal is recommended. For substantial overdose or severely symptomatic patients, activated charcoal may be administered repeatedly. Administration of cholestyramine may be useful following an overdose.
Hypersensitivity to meloxicam or to one of the excipients. The possibility exists of crossover sensitivity with aspirin and other non- steroidal antiinflammatory drugs (NSAIDs).
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 NSAIDs.
Severe hepatic failure.
Severe heart failure.
Non-dialyzed severe renal failure.
Children aged under 15.
Pregnancy (see Pregnancy and lactation).
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders.
Warning: RISK OF GI ULCERATION, BLEEDING AND PERFORATION WITH NSAID.
Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early in theraphy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Patients with prior history of serious GI events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.
Precautions: Cardiovascular Thrombotic Events: Observational studies have indicated that non- selective NSAIDs may be associated with an increased risk of serious cardiovascular events, principally myocardial infarction, which may increase with dose or duration of use. Patients with cardiovascular disease or cardiovascular risk of an adverse cardiovascular event in patient taking NSAID, especially in those with cardiovascular risk factors, the lowest effective dose should be used for the shortest possible duration. There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.
Hypertension: NSAIDs may lead to the onset of new hypertension or worsening the pre- existing hypertension and patients taking antihypertensive with NSAIDs may have an impaired antihypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.
Heart Failure: Fluid retention and oedema have been observed in some patients taking NSAIDs, there caution is advised in patients with fluid retention or heart failure.
Gastrointestinal Events: All NSAIDs can cause gastrointestinal discomfort and rarely serious, potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation which may increase with dose or duration of use, but can occur at any time without warning. Caution is advised in patients with risk factors for gastrointestinal events e.g. the elderly, those with a history of serious gastrointestinal events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patient about signs and symptoms of serious gastrointestinal toxicity. The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Severe Skin Reactions: NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash or any other sign of hypersensitivity.
Pregnancy: In animals, lethal effects on the embryo have been reported as doses far higher than those used clinically.
It is advisable to avoid the administration of meloxicam during pregnancy.
Lactation: it is unknown whether meloxicam passes into mothers milk. Meloxicam should not be given to nursing mothers.
Blood and the lymphatic system disorders: Anemia, disturbances of blood count: leucocytopenia; thrombocytopenia; there are isolated reports on agranulocytosis in patients taking meloxicam and other drugs with myelotoxic potential.
Immune system disorders: Rare: Anaphylactic / anaphylactoid reactions.
Psychiatric disorders: Rare: Mood disorders, insomnia and nightmares.
Nervous system disorders: Common: Light- headedness, headache. Uncommon: Vertigo, tinnitus, drowsiness. Rare: Confusion.
Eye disorders: Rare: Visual disturbances including blurred vision.
Cardiac disorders: Uncommon: Palpitations.
Vascular disorders: Uncommon: Increase in blood pressure, flushes.
Respiratory, thoracic and mediastinal disorders: Rare: Onset of asthma attacks in certain individuals allergic to aspirin or other NSAIDs.
Gastrointestinal disorders: Common: Dyspepsia, nausea and vomiting symptoms, abdominal pain, constipation, flatulence, diarrhea, oesophagitis, stomatitis. Uncommon: Gastrointestinal bleeding, gastroduodenal ulcers, esophagitis, stomatitis. Rare: Gastrointestinal perforation, gastritis, colitis.
The peptic ulcers, perforation or gastrointestinal bleeding, that may occur can be sometimes severe, especially in elderly.
Hepato biliary disorders: Rare: Hepatitis.
Skin and subcutaneous tissue disorder: Common: Pruritus, rash. Uncommon: Urticaria. Rare: Stevens-Johnson Syndrome and toxic epidermal necrolysis, angioedema, bullous reactions such as erythema multiforme, photosensitivity reactions.
Renal and urinary disorders: Uncommon: Sodium and water retention, hyperkalaemia, Rare: Acute functional renal failure in patients with risk factors.
General disorders and administration site conditions: Common: Edema including edema of the lower limbs.
Inadvisable combinations: Other NSAIDs, including high doses of salicylates: administration of several NSAIDs together may increase the risk of ulcers and of gastrointestinal bleeding, via a synergistic effect.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Anti-coagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin.
Oral anticoagulants, heparin and ticlopidine: increased risk of bleeding via inhibition of platelet function and damage to the gastroduodenal mucosa. Careful monitoring of the effects of anticoagulants is thus essential if it proves impossible to avoid such combined prescription.
Lithium: NSAIDs increase blood lithium levels, which may then reach toxic values ( decreased renal excretion of lithium). This parameter therefore requires monitoring during the initiation, adjustment and withdrawal of treatment with meloxicam.
Methotrexate: NSAIDs may accentuate the haematologic toxicity of methotrexate. A case of agranulocytosis with meloxicam has been reported in a patient who was also taking methotrexate. The direct causality of meloxicam was not confirmed, but caution is required before prescribing such a combination. Strict monitoring of blood cell count is recommended in this situation.
Intrauterine contraceptive devices: NSAIDs appear to decrease the efficacy of intrauterine contraceptive devices.
Combinations requiring precautions: Diuretics: treatment with NSAIDs is associated with a risk of acute renal failure in dehydrated patients (decreased glomerular filtration via decreased renal prostaglandin synthesis). In case of combined prescription of meloxicam and a diuretic, it is essential to ensure that the patient is adequately hydrated and to monitor renal function at the start of treatment.
Nephrotoxicity of cyclosporin may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combined treatment renal function is to be measured.
Associations needing to be taken into consideration: antihypertensive drugs [beta- blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics]: treatment with a NSAID may decrease their antihypertensive effect via inhibition of vasodilator prostaglandin synthesis.
Thrombolytics: increased risk of haemorrhage. Concomitant administration of antacids, cimetidine, β- acetyl digoxin and frusemide has not given rise to any notable pharmacokinetic interactions with meloxicam.
Cholestyramine accelerates the elimination of meloxicam via binding in the digestive tract. Interactions with oral anti- diabetics cannot be excluded.
M01AC06 - meloxicam ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, oxicams.
Tab 7.5 mg (light yellow, round, flat, 8mm diameter, cross-scored on one side) x 5 x 10's. 15 mg (light yellow, round, concave, 10mm diameter, scored on one side) x 5 x 10's.