Melsi

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MELSI

Composition:

Active substance: meloxicam;

1 tablet contains 7.5 mg or 15 mg of meloxicam;

Excipients: sodium citrate; lactose monohydrate; microcrystalline cellulose; povidone; colloidal anhydrous silicon dioxide; crospovidone; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: flat cylindrical tablets with bevelled edges and a score line on one side, light yellow in colour.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and anti-rheumatic drugs. Oxicams. ATC code M01A C06.

Pharmacological properties.

Pharmacodynamics.

Meloxicam is a non-steroidal anti-inflammatory drug exerting analgesic, antipyretic, and anti-inflammatory effects. The anti-inflammatory action is associated with inhibition of enzymatic activity of cyclooxygenase-2 (COX-2), which is involved in prostaglandin biosynthesis at the site of inflammation. To a lesser extent, meloxicam affects cyclooxygenase-1 (COX-1), which participates in the synthesis of prostaglandin protecting the gastrointestinal mucosa and involved in regulation of renal blood flow.

Pharmacokinetics.

Absorption.

Meloxicam is well absorbed from the gastrointestinal tract, regardless of food intake. The bioavailability of meloxicam is 89%. Steady-state concentration is reached by day 3–5 of treatment. Prolonged administration (over 6 months) does not lead to an increase in its plasma concentration compared to levels at the beginning of treatment.

Distribution.

Approximately 99% of the drug is bound to plasma proteins. Meloxicam penetrates into the synovial fluid, where its concentration is approximately half that in blood plasma. The volume of distribution averages 11 L.

Metabolism.

Biological transformation occurs in the liver via oxidation of methyl groups, resulting in the formation of 4 inactive metabolites.

Elimination.

Excretion of meloxicam occurs predominantly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged in feces, and a small amount in urine. The elimination half-life of the drug is 20 hours.

Plasma clearance is 8 mL/min and decreases in elderly individuals.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of osteoarthritis flare-up.

Long-term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis.

Contraindications.

• Hypersensitivity to meloxicam or any of the excipients of the medicinal product, or to active substances with similar action, such as NSAIDs, acetylsalicylic acid. Meloxicam should not be administered to patients who have experienced asthma, nasal polyps, angioedema, or urticaria after taking acetylsalicylic acid or other NSAIDs;
• Gastrointestinal bleeding or perforation related to previous NSAID therapy in medical history;
• Active or recurrent peptic ulcer/hemorrhage in medical history (two or more separate confirmed episodes of ulcer or bleeding);
• Severe hepatic impairment;
• Severe renal impairment without dialysis;
• Gastrointestinal bleeding, cerebrovascular bleeding in medical history, or other coagulation disorders;
• Severe heart failure;
• Contraindicated for the treatment of perioperative pain in coronary artery bypass grafting (CABG);
• Third trimester of pregnancy;
• Patient age under 16 years.

Interaction with other medicinal products and other forms of interaction.

Risks associated with hyperkalemia

Certain medicinal products or therapeutic groups may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), (low molecular weight or unfractionated) heparins, cyclosporine, tacrolimus, and trimethoprim.

The onset of hyperkalemia may depend on associated factors. The risk of hyperkalemia increases when the above-mentioned medicinal products are used concomitantly with meloxicam.

Pharmacodynamic interactions.

Other nonsteroidal anti-inflammatory agents and acetylsalicylic acid ≥ 3 g/dose. Combination with other NSAIDs, including acetylsalicylic acid at anti-inflammatory doses (≥ 500 mg per dose or ≥ 3 g total daily dose), is not recommended.

Corticosteroids (e.g., glucocorticoids). Concomitant use with corticosteroids requires caution due to an increased risk of gastrointestinal bleeding or ulceration.

Anticoagulants or heparin used in geriatric practice or at therapeutic doses. The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may potentiate the effects of anticoagulants such as warfarin. Concomitant use of NSAIDs and anticoagulants or heparin in geriatric practice or at therapeutic doses is not recommended.

In other cases (e.g., prophylactic doses), heparin use requires caution due to an increased risk of bleeding. Careful monitoring of INR (International Normalized Ratio) is necessary if such a combination cannot be avoided.

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 efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors or angiotensin II antagonists and cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Adequate hydration should be ensured, and renal function should be monitored after initiation of combined therapy and periodically thereafter.

Other antihypertensive agents (e.g., β-blockers). As with the agents listed below, a possible reduction in the antihypertensive effect of β-blockers may occur (due to inhibition of vasodilatory prostaglandins).

Calcineurin inhibitors (e.g., cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be enhanced by NSAIDs due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Careful monitoring of renal function is recommended, especially in elderly patients.

Intrauterine contraceptive devices. Reduced effectiveness of intrauterine contraceptive devices has been reported during NSAID use, but this requires further confirmation.

Deferasirox.

Concomitant use of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these medicinal products.

Pharmacokinetic interaction: effect of meloxicam on the pharmacokinetics of other medicinal products.

Lithium. Data exist for NSAIDs increasing plasma lithium concentrations (due to reduced renal excretion of lithium) to toxic levels. Concomitant use of lithium and NSAIDs is not recommended. If combination therapy is necessary, plasma lithium levels should be closely monitored at the start of treatment, during dose adjustment, and upon discontinuation of meloxicam.

Methotrexate. NSAIDs may reduce tubular secretion of methotrexate, thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high-dose methotrexate (more than 15 mg per week). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low-dose methotrexate, particularly those with impaired renal function. If combination therapy is required, blood parameters and renal function should be monitored. Caution is advised if NSAID and methotrexate administration continues for 3 consecutive days, as plasma methotrexate levels may rise and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg per week) were not affected by concomitant meloxicam treatment, hematological toxicity of methotrexate may increase during NSAID therapy (see information above).

Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance from 45 to 79 mL/min), meloxicam administration should be withheld for 5 days before, on the day of, and for 2 days after pemetrexed infusion. If combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, particularly for myelosuppression and gastrointestinal adverse reactions. Concomitant use of meloxicam with pemetrexed is not recommended in patients with severe renal impairment (creatinine clearance < 45 mL/min).

In patients with normal renal function (creatinine clearance ≥ 80 mL/min), a dose of 15 mg meloxicam may reduce pemetrexed elimination and thus increase the frequency of pemetrexed-related adverse reactions. Therefore, caution should be exercised when prescribing 15 mg meloxicam concomitantly with pemetrexed in patients with normal renal function (creatinine clearance ≥ 80 mL/min).

Pharmacokinetic interaction: effect of other medicinal products on the pharmacokinetics of meloxicam.

Cholestyramine. Cholestyramine accelerates the elimination of meloxicam due to disruption of enterohepatic circulation, resulting in a 50% increase in meloxicam clearance and a reduction in half-life to 13±3 hours. This interaction is clinically significant.

No clinically significant pharmacokinetic interactions were observed with concomitant administration of antacids, cimetidine, or digoxin.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and information on gastrointestinal and cardiovascular risks below).

The recommended maximum daily dose should not be exceeded if therapeutic effect is insufficient, and additional NSAIDs should not be used concomitantly, as this may increase toxicity without proven therapeutic benefit. Concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Meloxicam is not indicated for the relief of acute pain.

If no improvement is observed after several days of treatment, the clinical benefits of continued therapy should be re-evaluated.

Caution should be exercised in patients with a history of esophagitis, gastritis, and/or peptic ulcer to ensure complete treatment prior to initiating meloxicam therapy. Care should also be taken regarding possible recurrence in patients previously treated with meloxicam or those with such history.

Gastrointestinal disorders.

As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without prior warning symptoms or history of serious gastrointestinal disease.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. Such patients should begin treatment with the lowest effective dose. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risks, combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered (see information below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during initial stages of treatment.

Concomitant use of medicinal products that may increase the risk of ulceration or bleeding, such as heparin used as radical therapy or in geriatric practice, anticoagulants (e.g., warfarin), or other nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose, is not recommended with meloxicam.

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 disorders (ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated.

Hepatic disorders.

Up to 15% of patients receiving NSAIDs (including MELOXICAM) may experience elevated levels of one or more liver function tests. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations of ALT or AST (approximately 3 times or more above normal) have been observed in 1% of patients during NSAID studies. Rare cases of severe hepatic reactions, including jaundice, fulminant fatal hepatitis, hepatic necrosis, and hepatic failure, some with fatal outcomes, have also been reported.

If hepatic dysfunction is suspected or liver test abnormalities are observed, the patient should be evaluated for signs of more severe hepatic failure during treatment. If symptoms suggestive of liver disease develop or systemic manifestations occur (e.g., eosinophilia, rash), MELOXICAM should be discontinued.

Cardiovascular disorders.

Close monitoring is recommended in patients with arterial hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been observed during NSAID therapy.

Patients with cardiovascular risk factors should be monitored for blood pressure at the beginning of therapy, especially at the start of meloxicam treatment.

Available data suggest that use of certain NSAIDs (particularly at high doses and during long-term treatment) may slightly increase the risk of vascular thrombotic events (e.g., myocardial infarction or stroke). Insufficient data are available to exclude such risk with meloxicam.

NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk increases with duration of use. Patients with cardiovascular disease or cardiovascular risk factors have an increased risk.

Skin disorders.

Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported rarely during NSAID use. The highest risk of such reactions occurs early in treatment, with most cases appearing within the first month of therapy. At the first sign of skin rash, mucosal lesions, or other signs of hypersensitivity, meloxicam should be discontinued.

If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis during meloxicam treatment, the drug must not be re-administered at any time in the future.

Cases of fixed drug eruption have been reported with meloxicam use.

Meloxicam should not be re-prescribed to patients with a history of fixed drug eruption associated with meloxicam (see section "Adverse reactions").

Potential cross-reactivity may occur with other oxicams.

Anaphylactic reactions.

As with other NSAIDs, anaphylactic reactions may occur in patients without known prior sensitivity to MELOXICAM. The drug should not be used in patients with aspirin triad. This clinical complex occurs in patients with bronchial asthma who have experienced rhinitis with or without nasal polyps, or who have had severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Immediate measures for anaphylactoid reactions should be taken if such a reaction occurs.

Liver parameters and renal function.

As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, elevated serum bilirubin, or other liver function parameters, as well as increased serum creatinine and blood urea nitrogen, have been reported. In most cases, these abnormalities were mild and transient. If significant or persistent abnormalities occur, meloxicam should be discontinued and follow-up tests performed.

Functional renal impairment.

NSAIDs, by inhibiting the vasodilatory effect of renal prostaglandins, may induce functional renal impairment due to reduced glomerular filtration. This adverse effect is dose-dependent. Close monitoring of diuresis and renal function is recommended at the beginning of treatment or after dose increase in patients with the following risk factors:

• advanced age;
• concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, or diuretics;
• hypovolemia (of any origin);
• congestive heart failure;
• renal impairment;
• nephrotic syndrome;
• lupus nephropathy;
• severe hepatic dysfunction (serum albumin < 25 g/L or ≥ 10 according to Child-Pugh classification).

In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal papillary necrosis, or nephrotic syndrome.

The meloxicam dose in patients with end-stage renal impairment on dialysis should not exceed 7.5 mg. Dose reduction is not required in patients with mild to moderate renal impairment (creatinine clearance > 25 mL/min).

Sodium, potassium, and water retention.

NSAIDs may enhance sodium, potassium, and water retention and may interfere with the natriuretic effects of diuretics. Additionally, a reduced antihypertensive effect of antihypertensive drugs may occur. As a result, edema, heart failure, or arterial hypertension may worsen in susceptible patients. Therefore, clinical monitoring is recommended in such patients.

Hyperkalemia.

Hyperkalemia may be promoted by diabetes mellitus or concomitant use of drugs that increase potassium levels. In such cases, regular monitoring of potassium levels is required.

Combination with pemetrexed.

In patients with mild to moderate renal impairment receiving pemetrexed, meloxicam treatment should be withheld for at least 5 days before, on the day of, and for at least 2 days after pemetrexed administration.

Other warnings and safety measures.

Adverse reactions are often less well tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with treatment with other NSAIDs, caution is required in elderly patients, in whom reduced renal, hepatic, and cardiac function is more likely. Elderly patients have a higher incidence of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

Meloxicam, like any other NSAID, may mask symptoms of infectious diseases.

Meloxicam may negatively affect reproductive function and is not recommended for women wishing to become pregnant. Therefore, for women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam should be considered.

The product contains lactose; therefore, it is not recommended for patients with rare hereditary intolerance to galactose, lactase deficiency, or glucose-galactose malabsorption.

Masking of inflammation and fever.

The pharmacological effect of the drug in reducing fever and inflammation may complicate diagnosis in suspected non-infectious painful conditions.

Corticosteroid therapy.

MELOXICAM cannot be considered a substitute for corticosteroids in the treatment of corticosteroid insufficiency.

Hematological effects.

Anemia may occur in patients receiving NSAIDs, including MELOXICAM. This may be related to fluid retention, gastrointestinal bleeding of unknown origin, or microscopic or macroscopic blood loss, or to a partially unexplained effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients undergoing long-term NSAID therapy, including meloxicam, if symptoms of anemia are present.

NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike acetylsalicylic acid, their effect on platelet function is quantitatively less, short-term, and reversible. Patients taking MELOXICAM who may have adverse effects on platelet function, particularly coagulation disorders, and patients receiving anticoagulants should be carefully monitored.

Use in patients with asthma.

Patients with asthma may have aspirin-sensitive asthma. Use of acetylsalicylic acid (aspirin) in patients with aspirin-sensitive asthma is associated with severe bronchospasm, which may be fatal. Due to cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs, MELOXICAM should not be used in patients sensitive to acetylsalicylic acid (aspirin) and should be used with caution in patients with bronchial asthma.

Use during pregnancy or breastfeeding.

Fertility. Meloxicam, like other medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, may negatively affect reproductive function and is not recommended for women wishing to become pregnant. Therefore, for women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam should be considered.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and congenital heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to about 1.5%. This risk is considered to increase with higher doses and longer duration of treatment. Use of meloxicam from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation of the drug. Additionally, cases of fetal ductus arteriosus constriction have been reported after second-trimester use, most of which resolved after discontinuation of treatment. Therefore, meloxicam should not be used during the first and second trimesters of pregnancy, except when absolutely necessary. For women attempting to conceive and during the first and second trimesters of pregnancy, doses and duration of meloxicam treatment should be minimized. Prenatal monitoring for oligohydramnios and fetal ductus arteriosus constriction should be considered if meloxicam exposure occurs for several days starting from the 20th gestational week. Pregnant women should discontinue meloxicam if oligohydramnios or fetal ductus arteriosus constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors pose risks to the fetus:

• cardiopulmonary toxicity (with premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligohydramnios.

Risks to the mother at late stages of pregnancy and to the newborn:

• potential prolongation of bleeding time, anti-aggregatory effect even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, meloxicam is contraindicated during the third trimester of pregnancy.

Breastfeeding. Although specific data on this product are lacking, NSAIDs are known to pass into breast milk; therefore, use is not recommended in women who are breastfeeding.

Ability to influence reaction speed while driving or operating machinery.

No specific studies on the effect of the drug on the ability to drive or operate machinery have been conducted. Based on the pharmacodynamic profile and observed adverse reactions, meloxicam is unlikely to affect or has a negligible effect on such activities. However, patients who experience visual disturbances, including blurred vision, dizziness, somnolence, vertigo, or other central nervous system disorders, are advised to refrain from driving or operating machinery.

Method of Administration and Dosage

Administer orally.

The total daily dose should be taken once daily with water or another liquid, during a meal.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. The patient's need for symptomatic relief and response to treatment should be periodically evaluated.

Acute exacerbation of osteoarthritis:

7.5 mg/day (1 tablet of 7.5 mg or half a tablet of 15 mg). If necessary, the dose may be increased to 15 mg/day (1 tablet of 15 mg or 2 tablets of 7.5 mg).

Rheumatoid arthritis, ankylosing spondylitis:

15 mg/day (1 tablet of 15 mg or 2 tablets of 7.5 mg).

See also section "Special Patient Populations".

Depending on the therapeutic effect, the dose may be reduced to 7.5 mg/day (1 tablet of 7.5 mg or half a tablet of 15 mg).

Do not exceed the dose of 15 mg/day.

Special Patient Populations

Elderly patients and patients with an increased risk of adverse reactions

The recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg per day. Patients at increased risk of developing adverse reactions should start treatment with 7.5 mg per day.

Renal impairment

In patients with severe renal impairment undergoing dialysis, the dose should not exceed 7.5 mg per day. Dose reduction is not required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 ml/min). For patients with severe renal impairment not undergoing dialysis, see section "Contraindications".

Hepatic impairment

Dose reduction is not required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".

Children

Contraindicated in children under 16 years of age.

Overdose

Symptoms of acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive treatment. Gastrointestinal bleeding may occur. Severe poisoning may lead to hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported during therapeutic use of NSAIDs and may also occur in overdose.

In case of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown that meloxicam elimination is accelerated by taking 4 oral doses of cholestyramine three times daily.

Side effects

Available data suggest that the use of some NSAIDs (particularly at high doses and with prolonged treatment) is associated with a certain increased risk of vascular thrombotic events (e.g., myocardial infarction or stroke).

Edema, arterial hypertension, and heart failure have been observed during NSAID therapy.

Most of the adverse effects observed are of gastrointestinal origin. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported. Gastritis has been observed less frequently.

Blood and lymphatic system disorders: Anemia, blood test abnormalities (including changes in white blood cell count), leukopenia, thrombocytopenia. Very rare cases of agranulocytosis have been reported.

Immune system disorders: Allergic reactions, excluding anaphylactic or anaphylactoid reactions; anaphylactic reaction, anaphylactoid reaction, including shock.

Psychiatric disorders: Mood changes, nightmares, confusion, disorientation, insomnia.

Nervous system disorders: Headache, dizziness, drowsiness.

Eye disorders: Visual disturbances including blurred vision; conjunctivitis.

Ear and labyrinth disorders: Vertigo, tinnitus.

Cardiovascular disorders: Palpitations, increased blood pressure, flushing.

Heart failure associated with NSAID treatment has been reported.

Respiratory system disorders: Bronchial asthma in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs, upper respiratory tract infections, cough.

Gastrointestinal disorders: Dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea, occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, eructation, colitis, gastroduodenal ulcer, esophagitis, gastrointestinal perforation.

Gastrointestinal bleeding, ulceration, or perforation may be severe and potentially fatal, particularly in elderly patients.

Hepatobiliary disorders: Abnormal liver function tests (e.g., elevated transaminases or bilirubin), hepatitis, jaundice, hepatic failure.

Skin and subcutaneous tissue disorders: Angioneurotic edema, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, bullous dermatitis, erythema multiforme, photosensitivity reactions, exfoliative dermatitis. Fixed drug eruption (see section "Special precautions") – frequency unknown.

Renal and urinary disorders: Sodium and water retention, hyperkalemia, changes in renal function tests (increased serum creatinine and/or urea), acute renal failure, particularly in patients with risk factors, urinary tract infections, altered frequency of urination.

General disorders: Edema, including peripheral edema; influenza-like symptoms.

Musculoskeletal and connective tissue disorders: Arthralgia, back pain, joint-related symptoms.

Specific serious and/or common adverse reactions.

Very rare cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic medicinal products.

Adverse reactions not observed during use of the drug but typical for other compounds of the class.

Organic renal damage, which may lead to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 2 blisters per carton.

Prescription category.

Prescription only.

Marketing Authorization Holder: LLC "Representation BAUM PHARM GmbH".

Address of Marketing Authorization Holder: 66 Shyroka St., Lviv, 79052, Ukraine.

Manufacturer:

LLC "ASTRAFARM", Ukraine.

Manufacturer's address and site of operations:

6 Kyivska St., Vyshneve, Buchanskyi district, Kyiv region, 08132, Ukraine