Revmoxicam solution for intramuscular injection 15mg/1.5ml in ampoules 1.5ml №5×1

Name:
Revmoxicam solution for i/m introduction. 15mg/1.5ml in amp. 1.5 ml in bl. in pack. No. 5×1
Description:
Transparent yellow or greenish-yellow liquid The main active ingredient is meloxicam Release form Solution for intramuscular injection Dosage 15 mg / 1.5 ml Pharmacological properties Pharmacodynamics Revmoxicam is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, which has anti-inflammatory, analgesic and antipyretic effects. Meloxicam showed 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 inflammatory mediators. PharmacokineticsAbsorption. Meloxicam is completely absorbed after intramuscular injection. Relative bioavailability compared to oral administration is almost 100%. Therefore, it is not necessary to adjust the dose when switching from intramuscular to oral administration. After an intramuscular injection of 15 mg, the maximum plasma concentration is about 1.6-1.8 μg / ml and is reached in 1-6 hours. Distribution. Meloxicam binds very strongly to plasma proteins, mainly to albumin (99%). Meloxicam penetrates into the synovial fluid, where its concentration is half that in blood plasma. The volume of distribution is low, averaging 11 liters after intramuscular or intravenous administration, and shows individual variations in the range of 7-20%. The volume of distribution after the use of multiple oral doses of meloxicam (7.5 to 15 mg) is 16 liters with a deviation coefficient ranging from 11% to 32%. Biotransformation. Meloxicam is subject to extensive biotransformation in the liver. In urine, 4 different metabolites of meloxicam have been identified that are pharmacodynamically inactive. The main metabolite, 5′-carboxymeloxicam (60% of the dose), is formed by oxidation of the intermediate metabolite 5′-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies suggest that CYP 2C9 plays an important role in the metabolic process, while CYP 3A4 isoenzymes play a lesser role. Peroxidase activity in patients may be responsible for two other metabolites, which account for 16% and 4% of the prescribed dose, respectively. Elimination. Removal of meloxicam occurs mainly in the form of 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. The half-life is from 13 to 25 hours, depending on the route of administration (oral, intramuscular or intravenous). Plasma clearance is about 7-12 ml / min after a single oral dose, intravenous or rectal administration. dose linearity. Meloxicam shows linear pharmacokinetics within a therapeutic dose of 7.5 mg to 15 mg after oral and intramuscular administration. Special groups of patients. Patients with hepatic/renal insufficiency. Mild to moderate hepatic and renal insufficiency does not significantly affect the pharmacokinetics of meloxicam. Patients with moderate renal insufficiency had a significantly higher total clearance. Reduced plasma protein binding has been observed in patients with end-stage renal disease. In end-stage renal failure, an increase in the volume of distribution may lead to an increase in the concentration of free meloxicam. Do not exceed a daily dose of 7.5 mg (see section “Method of application and dosage”). Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, the AUC value 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. Indications for use Short-term symptomatic treatment of exacerbation of rheumatoid arthritis or ankylosing spondylitis in case of impossibility of using drugs orally or rectally. Method of administration and doses Intramuscular application. One injection of 15 mg 1 time per day. DO NOT EXCEED 15 mg/day. Treatment should be limited to one injection at the beginning of therapy, the maximum duration of therapy is up to 2-3 days in justified exceptional cases (for example, 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 of treatment necessary to control symptoms (see Precautions section). The patient’s need for symptomatic relief and response to treatment should be periodically assessed. Special categories of patients. Elderly patients and patients with an increased risk of adverse reactions. The recommended dose for elderly patients is 7.5 mg per day. Patients with an increased risk of adverse reactions should start treatment with 7.5 mg per day (half a 1.5 ml ampoule) (see section “Precautions”). Renal failure. For patients with severe renal insufficiency who are on dialysis, the dose should not exceed 7.5 mg per day (half a 1.5 ml ampoule). Patients with moderate and moderate renal insufficiency (namely, patients with creatinine clearance above 25 ml / min) dose reduction is not required. For patients with severe renal insufficiency without dialysis, see section “Contraindications”. Liver failure. Patients with mild to moderate hepatic insufficiency do not need a dose reduction. For patients with severe hepatic insufficiency, see section “Contraindications”. Mode of application. The drug should be administered slowly, by deep intramuscular injection into the upper outer quadrant of the buttock, adhering to strict aseptic technique. In case of repeated administration, it is recommended to alternate the left and right buttocks. Before injection, it is important to check that the needle point is not in the vessel. The injection should be stopped immediately in case of severe pain during the injection. If the patient has a hip prosthesis, the injection should be given in the other buttock. You can only use a clear solution that does not contain any inclusions. Precautions Adverse reactions can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to control symptoms (see section “Method of application and dosage” and information on gastrointestinal and cardiovascular risks below). The recommended maximum daily dose should not be exceeded in case of insufficient therapeutic effect, and additional NSAIDs should not be used, as this may increase toxicity, while therapeutic benefits have not been proven. The simultaneous use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Meloxicam should not be used to treat patients in need of acute pain relief. If there is no improvement after several days, the clinical benefits of treatment should be reassessed. Attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer in order to ensure their complete cure before starting meloxicam therapy. Regular attention should be paid due to the possible occurrence of relapse in patients treated with meloxicam and patients with a history of such cases. Gastrointestinal disorders. As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, regardless of prior symptoms or history of serious gastrointestinal disease. The risk of gastrointestinal bleeding, ulcers or perforation is higher with increasing doses of NSAIDs in patients with a history of ulcers, especially those complicated by bleeding or perforation (see section “Contraindications”), and in elderly patients. Such patients should begin treatment with the lowest effective dose. For such patients, combination therapy with protective drugs (such as misoprostol or proton pump inhibitors) may be appropriate. This also applies to patients who require the concomitant use of a low dose of aspirin or other medicinal products that increase gastrointestinal risks (see the information below and the section “Interaction with other medicinal products”). Patients with a history of gastrointestinal disease, especially elderly patients, should report all unusual abdominal symptoms (especially gastrointestinal bleeding), especially in the initial stages of treatment. Patients who are concomitantly taking medicinal products that increase the risk of ulcer or bleeding, such as heparin, as radical therapy or in geriatric practice, anticoagulants, such as warfarin, or other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid at anti-inflammatory doses (≥ 500 mg per reception or ≥ 3 g of the total daily dose), the use of meloxicam is not recommended (see section “Interaction with other medicinal products”). If gastrointestinal bleeding or ulcers occur in patients treated with 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 worsen (see section “Side Effects”). Liver disorders. Up to 15% of patients taking NSAIDs (including Revmoxicam) may have an increase in the values of one or more liver tests. Such laboratory abnormalities may be progressive, may remain unchanged, or may be transient with continued treatment. Significant increases in ALT or AST (approximately 3 times or more above normal) were noted in 1% of patients during clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, hepatic necrosis and liver failure, some of them fatal, have been reported during clinical trials with NSAIDs. Patients with symptoms of hepatic dysfunction or abnormal liver tests should be evaluated for the development of symptoms of more severe hepatic impairment during therapy with Reumoxicam. If clinical symptoms suggest the development of hepatic disease or if systemic manifestations of the disease are observed (eg eosinophilia, rash), then the use of Revmoxicam should be discontinued. Cardiovascular disorders. For patients with arterial hypertension and / or with a history of mild to moderate congestive heart failure, careful monitoring is recommended, since fluid retention and edema have been observed during NSAID therapy. For patients with risk factors, clinical monitoring of blood pressure at the beginning of therapy, especially at the beginning of the course of treatment with meloxicam, is recommended. Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) is associated with a small increase in the risk of vascular thrombotic events (such as myocardial infarction or stroke). There are insufficient data to rule out such a risk with meloxicam. Patients with uncontrolled hypertension, congestive heart failure, established coronary artery disease, peripheral arterial disease and/or cerebrovascular disease should only be treated with meloxicam after careful evaluation. Such an examination is necessary before starting long-term treatment in patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidemia, diabetes mellitus, smokers). NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. The increase in risk is associated with the duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease have an increased risk of thrombotic complications. Skin disorders. Severe life-threatening skin lesions have been reported: Stevens-Johnson syndrome and toxic epidermal necrolysis with meloxicam. Patients should be informed about the symptoms of severe lesions and closely monitored for skin reactions. The greatest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis exists during the first weeks of treatment. If the patient has symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (eg, progressive skin rash often with vesicles or mucosal involvement), treatment with meloxicam should be discontinued. It is important to diagnose and stop the use of any drugs that can cause severe Stevens-Johnson syndrome or toxic epidermal necrolysis as soon as possible. Associated with this is a better prognosis for severe skin lesions. If a patient is diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis while using meloxicam, the use of the drug should not be restored in the future. Anaphylactic reactions. As with other NSAIDs, anaphylactic reactions may occur in patients with no known reaction to Revmoxicam. Rheumoxicam should not be used in patients with the aspirin triad. This symptomatic complex occurs in patients with asthma who have had rhinitis, with or without nasal polyps, or who have experienced severe, potentially fatal bronchospasm following the use of aspirin or other NSAIDs. Emergency measures should be taken if an anaphylactic reaction is detected. Liver parameters and kidney function. As with most NSAIDs, isolated cases of elevated serum transaminases, serum bilirubin or other liver function parameters, elevated serum creatinine and blood urea nitrogen, and other laboratory abnormalities have been reported. In most cases, these deviations were minor and temporary. With significant or persistent confirmation of such deviations, the use of meloxicam should be discontinued and control tests should be carried out. Functional renal failure. NSAIDs, due to the inhibition of the vasodilating 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 such risk factors: – advanced age; – simultaneous use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section “Interaction with other drugs”); – hypovolemia (of any origin); – congestive heart failure; – renal failure; – nephrotic syndrome; – lupus nephropathy; – severe hepatic dysfunction (serum albumin < 25 g / l or ≥ 10 g / l according to the Child-Pugh classification). In isolated 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 insufficiency, the dose may not be reduced (creatinine clearance more than 25 ml / min). Retention of sodium, potassium and water. NSAIDs may increase sodium, potassium and water retention and affect the natriuretic effect of diuretics. In addition, there may be a decrease in the antihypertensive effect of antihypertensive drugs (see section "Interaction with other drugs"). As a result, sensitive patients may develop or worsen edema, heart failure, or hypertension. Therefore, patients at risk of sodium, potassium and water retention are advised to conduct clinical monitoring (see sections "Method of application and dosage" and "Contraindications"). Hyperkalemia. Hyperkalemia may be promoted by diabetes mellitus or the simultaneous use of drugs that increase potassium (see section "Interaction with other drugs"). In such cases, you need to regularly monitor the level of potassium. combination with pemetrexed. In patients with mild to moderate renal impairment receiving pemetrexed, treatment with meloxicam should be suspended for at least 5 days prior to pemetrexed administration, on the day of administration, and for at least 2 days after administration (see section "Interaction with other medicinal products") Other warnings and safety precautions. Adverse reactions are worse tolerated by elderly patients, weak or debilitated patients who need careful monitoring. As with other NSAIDs, caution should be exercised in elderly patients 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 "Method of application and dosage"). Meloxicam, like any other NSAID, can mask the symptoms of infectious diseases. As with intramuscular use of other NSAIDs, an abscess or necrosis may occur at the injection site. The use of meloxicam can adversely affect reproductive function and is not recommended for women who want to become pregnant. Therefore, for women who are planning to become pregnant or who are undergoing investigation for infertility, it may be advisable to stop taking meloxicam (see "Use during pregnancy or lactation"). Masking inflammation and fever. The pharmacological action of Revmoxicam to reduce fever and inflammation may complicate the diagnosis of suspected non-infectious pain syndrome. Treatment with corticosteroids. Rheumoxicam is not a likely substitute for corticosteroids in the treatment of corticosteroid deficiency. hematological effects. Anemia may occur in patients receiving NSAIDs, including Revmoxicam. This may be due to fluid retention, gastrointestinal bleeding of unknown origin, gross bleeding, or an incompletely described effect on erythropoiesis. In patients on long-term treatment with NSAIDs, including Revmoxicam, hemoglobin or hematocrit should be monitored if symptoms of anemia are present. NSAIDs inhibit platelet aggregation and may increase bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively smaller, transient and reversible. Patients who are prescribed Revmoxicam and who may have adverse effects on platelet function, such as bleeding disorders, as well as patients who receive anticoagulants, need careful monitoring. Use in patients with asthma. Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma is associated with severe bronchospasm, which can be fatal. Due to cross-reaction, including bronchospasm, between aspirin and other NSAIDs, Revmoxicam should not be used in aspirin-sensitive patients and should be used cautiously in patients with asthma. The medicinal product contains less than 1 mmol sodium (23 mg) per 1.5 ml ampoule, i.e. essentially free of sodium. Use during pregnancy and breastfeeding. Fertility. Meloxicam, like other drugs that inhibit the synthesis of cyclooxygenase / prostaglandin, can adversely affect reproductive function and is not recommended for women who want to become pregnant. Therefore, for women who are planning a pregnancy or undergoing fertility testing, discontinuation of meloxicam should be considered. Pregnancy. Inhibition of prostaglandin synthesis can adversely affect pregnancy and/or embryonic/fetal development. Data from epidemiological studies suggest an increased risk of miscarriage, heart defects and gastroschisis after the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of developing heart defects increased from less than 1% to about 1.5%. This risk is believed to increase with increasing dose and duration of treatment. During the 1st and 2nd trimesters of pregnancy, meloxicam should not be used unless absolutely necessary. For a woman who is trying to become pregnant or during the first and second trimester of pregnancy, the dose and duration of treatment with meloxicam should be minimal. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can create a risk for the fetus: - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); - impaired renal function, which can develop into renal failure with oligohydramnios. Risks in the last stages of pregnancy for the mother and newborn: - the possibility of lengthening the bleeding time, antiaggregatory effect, even at very low doses; - inhibition of uterine contractions, which leads to a delay or delay in childbirth. Therefore, meloxicam is contraindicated during the third trimester of pregnancy. Lactation. Although there are no specific data on Revmoxicam, NSAIDs are known to pass into breast milk. Therefore, the use is not recommended for women who are breastfeeding. Application in pediatrics. Revmoxicam, solution for intramuscular injection 15 mg / 1.5 ml, is contraindicated in children (under 18 years of age). Application for persons with operator activities and persons driving vehicles. There are no special studies on the effect of the drug on the ability to drive a car or work with other mechanisms. However, based on the pharmacodynamic profile and observed adverse reactions, it can be assumed that meloxicam has no or negligible effect on this activity. However, patients who have experienced visual impairment, including blurred vision, dizziness, drowsiness, vertigo, or other disorders of the central nervous system, are advised to refrain from driving or operating other mechanisms. Interactions with other drugs Interaction studies have only been conducted in adults. Risks associated with hyperkalemia. Some drugs may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs, (low molecular weight or unfractionated) heparins, cyclosporine, tacrolimus, and trimethoprim. The onset of hyperkalemia may depend on whether there are associated factors. The risk of hyperkalemia increases if the above drugs are used simultaneously with meloxicam. Pharmacodynamic interactions. Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/day. Combination with other NSAIDs is not recommended (see section "Precautions"), including acetylsalicylic acid in doses ≥ 500 mg at a time or ≥ 3 g of the total daily dose. Corticosteroids (eg glucocorticoids). Simultaneous use with corticosteroids requires caution due to an increased risk of bleeding or ulceration in the gastrointestinal tract. Anticoagulants or heparin. Significantly increases the risk of bleeding due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin (see Precautions section). The simultaneous use of NSAIDs and anticoagulants or heparin in geriatric practice or in therapeutic doses is not recommended. In connection with intramuscular administration, the solution for intramuscular administration of meloxicam is contraindicated in patients undergoing treatment with anticoagulants (see sections "Contraindications" and "Precautions"). In other cases (for example, at prophylactic doses), the use of heparin requires caution due to an increased risk of bleeding. Thrombolytic and antiplatelet drugs. 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 (eg, patients with dehydration 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. insufficiency, which is usually reversible. Therefore, the combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and their kidney function should be monitored after initiation of concomitant therapy and periodically thereafter (see Precautions section). Other antihypertensive drugs (eg beta-blockers). As with the use of the above drugs, a decrease in the antihypertensive effect of beta-blockers may develop (due to inhibition of prostaglandins with a vasodilating effect). Calcineurin inhibitors (eg cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs by mediating the effects of renal prostaglandins. During treatment, kidney function should be monitored. Careful monitoring of renal function is recommended, especially in elderly patients. Deferasirox. The concomitant use of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these drugs. Pharmacokinetic interaction: the effect of meloxicam on the pharmacokinetics of other drugs. Lithium. There is evidence of NSAIDs that increase plasma lithium levels (by decreasing renal excretion of lithium), which can reach toxic levels. The simultaneous use of lithium and NSAIDs is not recommended (see section "Precautions"). If combination therapy is necessary, plasma lithium levels should be carefully monitored at the start of treatment, when adjusting the dose, and when discontinuing treatment with meloxicam. Methotrexate. NSAIDs can reduce tubular secretion of methotrexate, thereby increasing its concentration in blood plasma. For this reason, it is not recommended to co-administer NSAIDs to patients taking a high dose of methotrexate (greater than 15 mg/week) (see Precautions section). The risk of interaction between NSAIDs and methotrexate should also be considered in patients who take a low dose of methotrexate, incl. patients with impaired renal function. If combined treatment is required, it is necessary to monitor blood counts and kidney function. Caution should be exercised when taking NSAIDs and methotrexate for 3 consecutive days, as the plasma level of methotrexate may increase and increase toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) was not affected by concomitant treatment with meloxicam, it should be considered that the hematological toxicity of methotrexate may increase with the treatment of NSAIDs (see above, as well as the "Side Effects" section). Pemetrexed. When meloxicam is co-administered with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45 to 79 ml/min), meloxicam should be withheld for 5 days prior to pemetrexed administration, on the day of administration, and 2 days after administration. If the combination of meloxicam with pemetrexed is necessary, patients should be carefully monitored, especially for the occurrence of myelosuppression and gastrointestinal adverse reactions. In patients with severe renal insufficiency (creatinine clearance below 45 ml/min), the concomitant use of meloxicam with 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 meloxicam 15 mg concomitantly with pemetrexed in patients with normal renal function (creatinine clearance ≥ 80 ml/min). Pharmacokinetic interaction: the effect of other drugs on the pharmacokinetics of meloxicam. Cholestyramine accelerates the elimination of meloxicam by disrupting intrahepatic circulation, so the clearance of meloxicam is increased by 50%, and the half-life is reduced to 13 ± 3 hours. This interaction is clinically significant. There was no clinically significant pharmacokinetic interaction when taken simultaneously with antacids, cimetidine and digoxin. Contraindications - Hypersensitivity to meloxicam or other ingredients of the drug, or to active substances with a similar effect, such as NSAIDs, aspirin. Meloxicam should not be given to patients who develop asthma symptoms, nasal polyps, angioedema, or urticaria after taking aspirin or other NSAIDs; - gastrointestinal bleeding or perforation associated with previous NSAID therapy in history; – history of active or recurrent peptic ulcer/bleeding (two or more separate confirmed cases of ulcer or bleeding); - severe liver failure; - severe renal failure without dialysis; - gastrointestinal bleeding, history of cerebrovascular bleeding or other blood clotting disorders; - disorders of hemostasis or the simultaneous use of anticoagulants (contraindications are associated with the route of administration); - severe heart failure; – treatment of perioperative pain in coronary artery bypass grafting (CABG); - III trimester of pregnancy (see "Use during pregnancy and the period of breastfeeding"); - the age of the patient is up to 18 years. Active ingredient: meloxicam; 1.5 ml of the drug contains meloxicam 15 mg; excipients: meglumine (N-methylglucamine), glycine, poloxamer 188, glycofurol, sodium chloride, 0.1 M sodium hydroxide solution, water for injection. Overdose Symptoms of acute overdose of NSAIDs are usually limited to lethargy, drowsiness, nausea, vomiting and epigastric pain, which are generally reversible with maintenance therapy. Gastrointestinal bleeding may occur. Severe poisoning can lead to hypertension, acute renal failure, liver dysfunction, respiratory depression, coma, convulsions, cardiovascular failure and cardiac arrest. Anaphylactoid reactions have been reported with the therapeutic use of NSAIDs, which can also occur with overdose. In case of an overdose of NSAIDs, symptomatic and supportive measures are recommended for patients. Studies have shown accelerated elimination of meloxicam with 4 oral doses of cholestyramine 3 times daily. Side effects Research data and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a slight increase in the risk of vascular thrombotic events (such as myocardial infarction or stroke) (see section "Precautions" ). Edema, arterial hypertension and heart failure have been observed in the treatment of NSAIDs. Most observed side effects are of gastrointestinal origin. Possible peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients (see Precautions section). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, vomiting of blood, ulcerative stomatitis, exacerbation of colitis and Crohn's disease were observed after use (see section "Precautions"). Gastritis was observed with less frequency. There have been reports of severe skin lesions: Stevens-Johnson syndrome and toxic epidermal necrolysis (see Precautions section). Adverse reactions are presented in accordance with the classification of organ systems and the frequency of occurrence: very often (≥ 1/10), often (≥1/100 to <1/10), infrequently (≥1/1000 to <1/100), rarely ( ≥1/10000 to <1/1000), very rare (<1/10000), not known (cannot be estimated based on available data). From the gastrointestinal tract: very often - digestive system disorders: dyspepsia, nausea, vomiting, abdominal pain, constipation, diarrhea, flatulence; infrequently - latent or macroscopic gastrointestinal bleeding, stomatitis, gastritis, belching; rarely - colitis, gastroduodenal ulcer, esophagitis; very rarely - gastrointestinal perforation. Gastrointestinal bleeding, ulceration, or perforation may be severe or potentially fatal, especially in elderly patients (see Precautions section). Frequency unknown - pancreatitis. From the hepatobiliary system: infrequently - a violation of liver function tests (for example, an increase in transaminases or bilirubin); very rarely - hepatitis; frequency unknown - jaundice, liver failure. On the part of the blood and lymphatic system: infrequently - anemia; rarely - deviation of blood test parameters from the norm (including a change in the number of leukocytes), leukopenia, thrombocytopenia. Cases of agranulocytosis have been reported (see Selected Serious and/or Frequent Adverse Reactions). From the immune system: infrequently - allergic reactions other than anaphylactic or anaphylactoid; frequency unknown - anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, including shock. On the part of the skin and subcutaneous tissue: infrequently - angioedema, itching, rash; rarely - urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis; very rarely - erythema multiforme, bullous dermatitis; frequency unknown - photosensitivity reactions, exfoliative dermatitis. On the part of the respiratory system, chest organs and mediastinum: rarely - asthma in patients allergic to acetylsalicylic acid and other NSAIDs; frequency unknown - respi