Instructions Melox solution for injection 15 mg/ml ampoule 1.5 ml No. 5
Composition
active ingredient: meloxicam;
1.5 ml of solution (1 ampoule) contains 15 mg of meloxicam;
excipients: meglumine, glycofurol, poloxamer 188, sodium chloride, glycine, sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent yellow or greenish-yellow solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A C06.
Pharmacological properties
Pharmacodynamics
Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the enolic acid class, which exhibits anti-inflammatory, analgesic and antipyretic effects. Meloxicam has shown high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its exact mechanism of action remains unknown. However, there is a common mechanism of action for all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, which are mediators of inflammation.
Pharmacokinetics
Absorption. Meloxicam is completely absorbed after intramuscular injection. The relative bioavailability compared to oral administration is almost 100%. Therefore, no dose adjustment is required when switching from the intramuscular to oral route of administration. After an intramuscular injection of 15 mg, the maximum plasma concentration (Cmax) is approximately 1.6-1.8 μg/ml and is reached in approximately 1-6 hours.
Distribution. Meloxicam is highly bound to plasma proteins, mainly albumin (99%). Meloxicam penetrates into the synovial fluid, where its concentration is half that in plasma. The volume of distribution is low, averaging 11 l after intramuscular or intravenous administration, and shows individual variations of 7-20%. The volume of distribution after multiple oral doses of meloxicam is 16 l with a coefficient of variation of 11% to 32%.
Biotransformation. Meloxicam undergoes extensive biotransformation in the liver. Four different metabolites of meloxicam, which are pharmacodynamically inactive, have been identified in the urine. The main metabolite 5'-carboxymeloxicam (60% of the dose) is formed by oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of the dose). In vitro studies suggest that CYP 2C9 plays an important role in the metabolism process, while CYP 3A4 isoenzymes play a minor role. Peroxidase activity in patients is probably responsible for the other two metabolites, which account for 16% and 4% of the administered dose, respectively.
Elimination: Meloxicam is excreted mainly as metabolites in equal parts with urine and feces. Less than 5% of the daily dose is excreted unchanged in the feces, a small amount is excreted in the urine from 13 to 25 hours depending on the route of administration (oral, intramuscular or intravenous). Plasma clearance is approximately 7-12 ml/min after a single oral dose, intravenous or rectal administration.
Dose linearity: Meloxicam exhibits linear pharmacokinetics in the therapeutic dose range of 7.5 mg to 15 mg after oral and intramuscular administration.
Patients with hepatic/renal insufficiency. Mild to moderate hepatic and renal insufficiency do not significantly affect the pharmacokinetics of meloxicam. Patients with moderate renal insufficiency had a significantly higher total clearance. Reduced binding to plasma proteins was observed in patients with end-stage renal failure. In end-stage renal failure, an increase in the volume of distribution may lead to an increase in the concentration of free meloxicam (see sections "Contraindications" and "Method of administration and dosage").
Elderly patients. In elderly male patients, the mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, the area under the pharmacokinetic curve (AUC) is higher and the half-life is longer compared to the corresponding values in young volunteers of both sexes. The mean plasma clearance at steady state in elderly patients was slightly lower than in young volunteers (see section 4.2).
Indication
Short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when oral and rectal routes of administration cannot be used.
Contraindication
III trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
patient's age is up to 18 years;
hypersensitivity to meloxicam or to other components of the drug, or to active substances with a similar effect, such as NSAIDs (acetylsalicylic acid); meloxicam should not be prescribed to patients who have experienced symptoms of asthma, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs;
history of active or recurrent peptic ulcer/bleeding (two or more separate confirmed episodes of ulceration or bleeding);
severe liver failure;
severe renal failure (without dialysis);
gastrointestinal bleeding, history of cerebrovascular bleeding, or other blood clotting disorders;
hemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration);
severe heart failure;
treatment of perioperative pain in coronary artery bypass grafting.
Interaction with other medicinal products and other types of interactions
Risks associated with hyperkalaemia. Some medicinal products or therapeutic classes may cause hyperkalaemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), ciclosporin, tacrolimus and trimethoprim. The onset of hyperkalaemia may depend on the presence of predisposing factors. The risk of hyperkalaemia is increased when the above-mentioned medicinal products are used concomitantly with meloxicam.
Pharmacodynamic interactions
Other NSAIDs and acetylsalicylic acid ≥ 3 g/day. Combination with other NSAIDs (see section "Special warnings and precautions for use"), acetylsalicylic acid in doses ≥ 500 mg (single dose) or ≥ 3 g (total daily dose) is not recommended.
Corticosteroids (e.g. glucocorticoids): Concomitant use with corticosteroids requires caution due to increased risk of gastrointestinal bleeding or ulceration.
Anticoagulants or heparin. The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special instructions"). The concomitant use of NSAIDs and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses. Due to the intramuscular administration, meloxicam solution for injection is contraindicated in patients receiving anticoagulant treatment (see sections "Contraindications" and "Special instructions").
In other cases (e.g., when using prophylactic doses), caution is required when using heparin due to the increased risk of bleeding.
Thrombolytic and antiplatelet agents: Increased risk of bleeding due to 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 impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function), the concomitant use of ACE inhibitors or angiotensin II antagonists and drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such a combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and renal function should be monitored after initiation of concomitant therapy and periodically thereafter (see section 4.4).
Other antihypertensive drugs (e.g. beta-blockers): As with the following drugs, the antihypertensive effect of beta-blockers may be reduced.
Calcineurin inhibitors (e.g., cyclosporine, tacrolimus). Nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Close monitoring of renal function is recommended, especially in elderly patients.
Deferasirox: Concomitant use of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these drugs.
Pharmacokinetic interaction: effect of meloxicam on the pharmacokinetics of other drugs
Methotrexate. NSAIDs may reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high doses of methotrexate (more than 15 mg/week) (see section "Special warnings and precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low doses of methotrexate, including patients with impaired renal function. If combined treatment is necessary, blood count and renal function should be monitored. Caution should be exercised when NSAIDs and methotrexate are taken for 3 consecutive days, as plasma levels of methotrexate may increase and toxicity may increase. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, it is believed that the hematological toxicity of methotrexate may be increased by treatment with NSAIDs (see section "Adverse reactions").
Pemetrexed. When meloxicam is co-administered with pemetrexed in patients with creatinine clearance between 45 and 79 ml/min, meloxicam should be discontinued 5 days before, on the day of, and for 2 days after pemetrexed administration. If the combination of meloxicam and pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastrointestinal adverse reactions. In patients with severe renal impairment (creatinine clearance below 45 ml/min), the co-administration of meloxicam and pemetrexed is not recommended.
In patients with normal renal function (creatinine clearance ≥ 80 ml/min), doses of 15 mg meloxicam may reduce the elimination of pemetrexed and, therefore, increase the incidence of adverse reactions associated with pemetrexed. Therefore, caution should be exercised when prescribing 15 mg meloxicam concomitantly with pemetrexed in patients with normal renal function (creatinine clearance ≥ 80 ml/min).
Effect of other drugs on the pharmacokinetics of meloxicam
Cholestyramine accelerates the elimination of meloxicam due to impaired intrahepatic circulation, so the clearance of meloxicam increases by 50% and the half-life decreases to 13±3 hours. This interaction is clinically significant.
Pharmacokinetic interaction: effect of the combination of meloxicam and other drugs on pharmacokinetics
Oral antidiabetic agents (sulfonylureas, nateglinide)
Meloxicam is almost completely eliminated by hepatic metabolism, approximately two-thirds of which is mediated by cytochrome (CYP) P450 enzymes (primary CYP 2C9 and minor CYP 3A4) and one-third by other pathways, such as peroxidase oxidation. The possibility of pharmacokinetic interactions should be considered when meloxicam is co-administered with medicinal products that are known to inhibit or are metabolised by CYP 2C9 and/or CYP 3A4. Interactions mediated by CYP 2C9 may be expected in combination with medicinal products such as oral antidiabetic agents (sulfonylureas, nateglinide); this interaction may lead to increased plasma levels of these medicinal products and meloxicam. Patients taking meloxicam and sulphonylureas or nateglinide should be closely monitored for hypoglycaemia.
No clinically significant pharmacokinetic interaction was found when co-administered with antacids, cimetidine, and digoxin.
Children: Interaction studies have only been conducted in adults.
Application features
Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 and information on gastrointestinal and cardiovascular risks below). The recommended maximum daily dose should not be exceeded in the event of insufficient therapeutic effect, and additional NSAIDs should not be used, as this may increase toxicity without proven therapeutic benefit. The concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Meloxicam should not be used to treat patients requiring relief of acute pain. If there is no improvement after several days, the clinical benefit of treatment should be reassessed.
Gastrointestinal disorders: As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration or perforation may occur at any time during treatment, with or without previous symptoms or a history of serious gastrointestinal disease. The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, especially complicated by bleeding or perforation (see section 4.3), and in the elderly. In such patients, treatment should be started at the lowest effective dose. Combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered for such patients, as well as for patients who require concomitant low-dose acetylsalicylic acid or other drugs that increase gastrointestinal risks (see information below and section 4.5).
Patients with a history of gastrointestinal toxicity, especially elderly patients, should be informed of any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.
The use of meloxicam is not recommended in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as heparin as a radical therapy or in geriatric practice, anticoagulants such as warfarin or other NSAIDs, including acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose (see section "Interaction with other medicinal products and other forms of interaction"). If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").
Liver disorders. Approximately 15% of patients taking NSAIDs (including Meloxicam) may have elevations in one or more liver function tests. These laboratory abnormalities may progress, remain stable, or be transient with continued treatment. Significant elevations in ALT or AST (approximately three times or more times the upper limit of normal) have been reported in 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which were fatal, have been reported in clinical trials with NSAIDs.
Patients with symptoms and/or signs of hepatic dysfunction or abnormal liver function tests should be evaluated for the development of more severe hepatic impairment while receiving Meloxicam. If clinical signs and symptoms consistent with liver disease develop or if systemic manifestations of the disease occur (e.g. eosinophilia, rash), the drug should be discontinued.
Cardiovascular disorders: Close monitoring is recommended in patients with hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and oedema have been reported with NSAID therapy.
Clinical monitoring of blood pressure is recommended in patients with risk factors at the beginning of therapy, especially at the beginning of treatment with meloxicam.
Clinical and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There are insufficient data to exclude such a risk for meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with meloxicam only after careful evaluation. Such evaluation is necessary before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
Skin disorders. Severe, life-threatening skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam. Patients should be informed of the signs and symptoms of severe skin reactions and should be closely monitored for skin reactions. The risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis is highest during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g. skin rash, often progressing to blisters or involving mucous membranes), meloxicam should be discontinued. It is important to promptly diagnose and discontinue any medicinal product that may cause Stevens-Johnson syndrome or toxic epidermal necrolysis. This is associated with a better prognosis in severe skin reactions. If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while taking meloxicam, the drug should not be restarted at any time in the future.
Cases of fixed drug eruption (FDE) have been reported with meloxicam. Meloxicam should not be re-administered to patients with a history of FDE associated with meloxicam. Cross-reactivity with other oxicams is possible.
Anaphylactic reactions. As with other NSAIDs, anaphylactic reactions may occur in patients with no known reaction to Melox. Melox should also not be used in patients with the aspirin triad. This symptom complex has been observed in patients with asthma who have reported rhinitis with or without nasal polyps or who have experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Emergency care should be sought if anaphylactic reactions occur.
Liver and kidney function: As with most NSAIDs, isolated cases of increased serum transaminases, serum bilirubin or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory abnormalities have been reported. In most cases, these abnormalities were minor and transient. If significant or persistent abnormalities occur, meloxicam should be discontinued and follow-up tests should be performed.
Functional renal failure. NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, can induce functional renal failure by reducing glomerular filtration. This side effect is dose-dependent. At the beginning of treatment or after increasing the dose, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors: elderly age; concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other types of interactions"); hypovolemia (of any origin); congestive heart failure; renal failure; nephrotic syndrome; lupus nephropathy; severe hepatic dysfunction (serum albumin < 25 g/l or ≥ 10 according to the Child-Pugh classification).
In rare cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.
The dose of meloxicam for patients with end-stage renal disease on dialysis should not exceed 7.5 mg. In patients with mild to moderate renal impairment (creatinine clearance >25 ml/min), the dose may not be reduced.
Sodium, potassium and water retention. NSAIDs may increase sodium, potassium and water retention and may interfere with the natriuretic effects of diuretics. In addition, the antihypertensive effect of antihypertensive drugs may be reduced (see section 4.5). As a result, edema, heart failure or hypertension may be precipitated or aggravated in susceptible patients. Therefore, clinical monitoring is recommended in patients at risk of sodium, potassium and water retention (see sections 4.3 and 4.4).
Hyperkalemia: Hyperkalemia may be caused by diabetes mellitus or concomitant use of medicinal products that increase potassium levels (see section 4.5). In such cases, potassium levels should be monitored regularly.
Other warnings and precautions. Adverse reactions are often worse tolerated in elderly, frail or debilitated patients who require close supervision. As with other NSAIDs, caution should be exercised in the elderly, who are more likely to have decreased renal, hepatic and cardiac function. Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Meloxicam, like any other NSAID, may mask the symptoms of infectious diseases.
As with other intramuscular NSAIDs, abscess or necrosis may occur at the injection site. Meloxicam may impair reproductive function and is therefore not recommended in women attempting to conceive. For women attempting to conceive or undergoing investigation of infertility, discontinuation of meloxicam should be considered (see section 4.6).
This medicinal product contains less than 1 mmol sodium (23 mg) per 1.5 ml ampoule, i.e. essentially sodium-free.
Masking of inflammation and fever. The pharmacological action of Melox, which is aimed at reducing fever and inflammation, may reduce the usefulness of diagnostic data in determining complications of a suspected non-infectious painful condition.
Corticosteroid treatment: Melox cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects. Anemia may occur in patients receiving NSAIDs, including Meloxicam. This may be due to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or an incompletely described effect on erythropoiesis. Patients on long-term treatment with NSAIDs, including Meloxicam, should have their hemoglobin or hematocrit monitored if they develop symptoms and signs of anemia.
NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. In contrast to acetylsalicylic acid, their effect on platelet function is quantitatively smaller, short-lived and reversible. Patients prescribed Melox who may have adverse reactions related to changes in platelet function, such as coagulation disorders, or patients receiving anticoagulants, require careful monitoring.
Use in patients with existing asthma. Patients with asthma may have aspirin-sensitive asthma. The use of acetylsalicylic acid in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which may be fatal. Due to cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs, Melox should not be used in patients sensitive to acetylsalicylic acid and should be used with caution in patients with existing asthma.
Use during pregnancy or breastfeeding
Fertility: For a woman attempting to conceive, the dosage and duration of treatment should be kept to a minimum.
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations has increased from less than 1% to approximately 1.5%. This risk is thought to increase with increasing dose and duration of treatment.
The use of meloxicam from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of the drug. In addition, narrowing of the ductus arteriosus in the fetus has been reported after administration of the drug in the second trimester of pregnancy, which in most cases disappeared after discontinuation of treatment. Therefore, meloxicam should not be used during the first and second trimesters of pregnancy unless absolutely necessary.
It may be advisable to monitor the fetus for oligohydramnios and ductus arteriosus in the event of exposure to meloxicam for several days, starting from the 20th week of gestation. Pregnant women should discontinue meloxicam if oligohydramnios or ductus arteriosus is detected.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose a risk to the fetus:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
kidney dysfunction.
Possible risks in the last stages of pregnancy for the woman and the fetus:
prolongation of bleeding time, anti-aggregation effect even at very low doses;
suppression of uterine contractions, leading to delayed or prolonged labor.
Therefore, meloxicam is contraindicated during the third trimester of pregnancy.
Breastfeeding. Although there are no specific data on Melox, NSAIDs are known to pass into breast milk. Therefore, the use of the drug is not recommended for women who are breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no specific studies on the effects of the drug on the ability to drive or use machines. However, based on the pharmacodynamic profile and the observed adverse reactions, meloxicam is likely to have no or negligible influence on these activities. However, patients who experience visual disturbances, including blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, are advised to refrain from driving or using machines.
Method of administration and doses
Intramuscular use. One injection of 15 mg once daily.
DO NOT EXCEED THE DOSE OF 15 mg/day.
Treatment should be limited to a single injection at the beginning of therapy with a maximum duration of up to 2-3 days in justified exceptional cases (e.g. when oral and rectal routes of administration are not possible). Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special instructions").
The patient's need for symptomatic relief and response to treatment should be assessed periodically.
Elderly patients (see section "Pharmacokinetics"). The recommended dose for elderly patients is 7.5 mg per day (half a 1.5 ml ampoule) (see section "Method of administration and dosage" 'Patients at increased risk of developing adverse reactions' and section "Special instructions for use").
Patients at increased risk of adverse reactions (see section 4.4). Patients at increased risk of adverse reactions, such as a history of gastrointestinal disease or risk factors for cardiovascular disease, should be started on 7.5 mg per day (half a 1.5 ml ampoule).
Renal impairment. This medicinal product is contraindicated in patients with severe renal impairment not on haemodialysis (see section 4.3). For patients with end-stage renal disease on haemodialysis, the dose should not exceed 7.5 mg/day (half a 1.5 ml ampoule). No dose reduction is required in patients with mild to moderate renal impairment (i.e. patients with creatinine clearance above 25 ml/min).
Hepatic impairment: No dose reduction is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".
Administration features. The drug should be administered slowly, by deep intramuscular injection into the upper outer quadrant of the buttock, observing strict aseptic technique. In case of repeated administration, it is recommended to alternate the left and right buttock. Before injection, it is important to check that the needle tip is not in a vessel. The injection should be stopped immediately in case of severe pain during the injection. In case of hip replacement, the injection should be made into the other buttock. For continued treatment, oral forms of the drug (tablets) should be used.
Children
Melox, solution for injection 15 mg/1.5 ml, is contraindicated in children under 18 years of age (see section "Contraindications").
Overdose
Symptoms of acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive therapy. Gastrointestinal bleeding may occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic use of NSAIDs, which may also occur with overdose.
In case of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown that meloxicam elimination is accelerated by 4 oral doses of cholestyramine 3 times daily.
Side effects
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke) (see section "Special warnings and precautions for use"). Edema, hypertension and heart failure have been observed in the treatment of NSAIDs. Most of the observed side effects are of gastrointestinal origin. Peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, may occur, especially in elderly patients (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section "Special warnings and precautions for use"). Gastritis has been observed less frequently after the use of the drug. Severe skin reactions have been reported: Stevens-Johnson syndrome and toxic epidermal necrolysis (see section "Special warnings and precautions for use").
Very rare cases of agranulocytosis have been reported (see “Selected serious and/or common adverse reactions”).
Immune system disorders: uncommon – allergic reactions, except anaphylactic or anaphylactoid reactions; frequency unknown – anaphylactic
