Meloxicam-vista

INSTRUCTIONS for medical use of the medicinal product MELOXICAM-VISTA (MELOXICAM-VISTA)

Composition:

Active substance: meloxicam;

1 ampoule (1.5 ml) contains meloxicam 15 mg;

Excipients: meglumine, glycofurol, poloxamer 188, sodium chloride, glycine, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear greenish-yellow solution, free from particles.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. ATC code M01A C06.

Pharmacological Properties

Pharmacodynamics

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, exhibiting anti-inflammatory, analgesic, and antipyretic effects. Meloxicam has demonstrated 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 shared by all NSAIDs (including meloxicam): inhibition of prostaglandin biosynthesis, which are mediators of inflammation.

Pharmacokinetics

Absorption. Meloxicam is completely absorbed after intramuscular injection. The relative bioavailability compared to oral administration is nearly 100%. Therefore, dose adjustment is not required when switching from intramuscular to oral administration. After intramuscular injection of 15 mg, the maximum plasma concentration (Cmax) is approximately 1.6–1.8 μg/mL and is reached within approximately 1–6 hours.

Distribution. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%). Meloxicam penetrates into synovial fluid, where its concentration is about half that in plasma. The volume of distribution is low, averaging 11 L after intramuscular or intravenous administration, with individual deviations within 7–20%. The volume of distribution after multiple oral doses of meloxicam (7.5 to 15 mg) is 16 L, with a coefficient of variation ranging from 11% to 32%.

Biological transformation. Meloxicam undergoes extensive biotransformation in the liver. Four different metabolites of meloxicam, which are pharmacodynamically inactive, have been identified in urine. The main metabolite, 5’-carboxymeloxicam (60% of dose), is formed via oxidation of the intermediate metabolite 5’-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of dose). In vitro studies suggest that CYP 2C9 plays a major role in the metabolism process, while CYP 3A4 isoenzymes play a minor role. Peroxidase activity in patients may be responsible for two other metabolites, accounting for 16% and 4% of the administered dose, respectively.

Elimination. Meloxicam is primarily excreted as metabolites in equal parts via urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, and a negligible amount is excreted in urine within 13–25 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.

Linearity of dose. Meloxicam exhibits linear pharmacokinetics within the therapeutic dose range of 7.5 mg to 15 mg following oral and intramuscular administration.

Special patient groups.

Patients with hepatic/renal impairment. Mild to moderate hepatic and renal impairment do not significantly affect the pharmacokinetics of meloxicam. Patients with moderate renal impairment showed significantly higher total clearance. Reduced plasma protein binding was observed in patients with end-stage renal disease. In end-stage renal disease, an increased volume of distribution may lead to increased free meloxicam concentration (see sections «Contraindications» and «Dosage and administration»). Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, the area under the plasma concentration-time curve (AUC) is higher and the elimination half-life is longer compared to young volunteers of both sexes. Mean plasma clearance at steady state in elderly patients was slightly lower than in young volunteers (see section «Dosage and administration»).

Clinical Characteristics

Indications. For short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when other routes of administration cannot be used. The medicinal product MELOXICAM-VISTA, solution for injection, is indicated for the treatment of adult patients.

Contraindications

• Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
• Patient age under 18 years;
• Hypersensitivity to meloxicam or to any of the excipients of the medicinal product, or to active substances with a similar action, such as NSAIDs (acetylsalicylic acid); meloxicam should not be administered to patients who experience symptoms of 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/bleeding 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;
• Hemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration);
• Severe heart failure;
• Not to be used for the treatment of perioperative pain in coronary artery bypass grafting.

Interaction with other medicinal products and other types of interactions

Risks associated with hyperkalemia. Some medicinal products or therapeutic groups may cause hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim. The development of hyperkalemia may depend on associated risk factors. The risk of hyperkalemia increases if the above-mentioned medicinal products are used concomitantly with meloxicam.

Pharmacodynamic interactions

Other NSAIDs and acetylsalicylic acid. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), acetylsalicylic acid at doses ≥ 500 mg (single dose) or ≥ 3 g (total daily dose).

Corticosteroids (e.g., glucocorticoids). Concomitant use with corticosteroids requires caution due to an 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 precautions for use"). Concomitant use of NSAIDs and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses. Due to intramuscular administration, meloxicam injection solution is contraindicated in patients undergoing anticoagulant therapy (see sections "Contraindications" and "Special precautions for use").

In other cases (e.g., when using prophylactic doses), caution is required during heparin use due to an increased risk of bleeding.

Thrombolytics and antiplatelet agents. Increased risk of gastrointestinal 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 medicinal products. 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 medicinal products may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. Therefore, such combination should be used with caution, especially in elderly patients. Patients should receive adequate fluid intake, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter (see section "Special precautions for use").

Other antihypertensive medicinal products (e.g., beta-blockers). As with the use of the medicinal products listed below, a reduction in the antihypertensive effect of beta-blockers is possible (due to inhibition of vasodilatory prostaglandins).

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

Deferasirox. Concomitant use of meloxicam and deferasirox increases 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 indicate that NSAIDs increase plasma lithium concentrations (due to reduced renal excretion of lithium), which may reach toxic levels. Concomitant use of lithium and NSAIDs is not recommended (see section "Special precautions for use"). If combination therapy is necessary, plasma lithium levels should be closely monitored at the beginning 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 (over 15 mg/week) (see section "Special precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered if the patient is receiving low-dose methotrexate, particularly in the presence of renal impairment. If combination therapy is required, blood counts and renal function should be monitored. Caution is advised when NSAIDs and methotrexate are taken for 3 consecutive days, as plasma methotrexate levels may increase and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, hematological toxicity of methotrexate is considered to potentially increase during NSAID therapy (see section "Adverse reactions").

Pemetrexed. In patients receiving concomitant meloxicam and pemetrexed with creatinine clearance between 45 and 79 mL/min, meloxicam should be withheld 5 days before, on the day of, and 2 days after pemetrexed administration. If combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, particularly for signs of myelosuppression and gastrointestinal adverse reactions. Concomitant use of meloxicam with pemetrexed is not recommended in patients with severe renal impairment (creatinine clearance below 45 mL/min). In patients with normal renal function (creatinine clearance ≥ 80 mL/min), 15 mg doses of meloxicam may reduce pemetrexed elimination and thus increase the frequency of pemetrexed-related adverse reactions. Therefore, 15 mg meloxicam should be prescribed with caution when used 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 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.

Pharmacokinetic interaction: effect of combination of meloxicam and other medicinal products on pharmacokinetics

Oral antidiabetic agents (sulfonylurea derivatives, nateglinide). Meloxicam is almost entirely eliminated via hepatic metabolism, approximately two-thirds mediated by cytochrome P450 (CYP) enzymes (mainly CYP 2C9 and secondary CYP 3A4) and one-third via other pathways, such as peroxidase oxidation. Potential pharmacokinetic interactions should be considered when meloxicam is administered concomitantly with medicinal products that strongly inhibit or are metabolized by CYP 2C9 and/or CYP 3A4. Interactions mediated by CYP 2C9 may be expected when combined with medicinal products such as oral antidiabetics (sulfonylurea derivatives, nateglinide); this interaction may lead to increased plasma levels of these medicinal products and meloxicam. Patients receiving meloxicam and sulfonylurea or nateglinide should be closely monitored for the development of hypoglycemia.

No clinically significant pharmacokinetic interaction was observed with concomitant administration of antacids, cimetidine, or digoxin.

Children. Interaction studies have been conducted only in adults.

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 the therapeutic effect is insufficient, and additional NSAIDs should not be used, as this may increase toxicity without proven therapeutic benefits. Concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Meloxicam should not be used for the treatment of patients requiring relief of acute pain. If no improvement is observed after several days, the clinical benefits of treatment should be re-evaluated.

Caution should be exercised in patients with a history of esophagitis, gastritis, and/or peptic ulcer to ensure complete treatment before initiating meloxicam therapy. The possibility of recurrence should always be considered in patients treated with meloxicam and in 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 preceding symptoms or serious gastrointestinal disease history. The risk of gastrointestinal bleeding, ulceration, or perforation is higher with increasing NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should start treatment with the lowest effective dose. For such patients, the use of concomitant protective agents (such as misoprostol or proton pump inhibitors) should be considered, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risks (see below in this section and section "Interaction with other medicinal products and other forms of interaction").

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

Use of meloxicam is not recommended in patients concurrently using drugs that increase the risk of ulceration or bleeding, such as heparin (as 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 disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").

Hepatic disorders. Approximately 15% of patients taking 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 increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (at least three times above normal) were observed in 1% of patients during clinical trials with NSAIDs. Additionally, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported during clinical trials with NSAIDs. Patients with symptoms and/or signs of hepatic dysfunction or abnormal liver test results should be monitored for the development of more severe hepatic failure during meloxicam treatment. If clinical signs of liver disease develop or systemic manifestations of disease occur (e.g., eosinophilia, rash), this medicinal product should be discontinued.

Cardiovascular and cerebrovascular disorders. Careful monitoring is recommended for patients with arterial hypertension and/or mild to moderate congestive heart failure history, as fluid retention and edema have been observed during NSAID therapy. Clinical monitoring of blood pressure is recommended at the start of therapy, especially at the beginning of meloxicam treatment, in patients with risk factors. Data from studies and epidemiological evidence suggest that the use of certain NSAIDs, including meloxicam (especially at high doses and for prolonged periods), is associated with a certain increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There is insufficient data to exclude such risk with meloxicam use. Meloxicam therapy should be prescribed to patients with uncontrolled arterial hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease only after careful evaluation. Such evaluation is necessary before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smokers). NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk increases with the duration of use. Patients with cardiovascular diseases or cardiovascular risk factors have an increased risk of thrombotic complications.

Skin disorders. Life-threatening severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam use. Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored for skin reactions. The highest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis occurs during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., progressive skin rashes, often with blisters or mucosal involvement), meloxicam treatment should be discontinued. It is crucial to diagnose promptly and discontinue any medicinal products that may cause severe skin reactions: Stevens-Johnson syndrome or toxic epidermal necrolysis. This is associated with a better prognosis in severe skin reactions. If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking meloxicam, this medicinal product must never be used again in the future.

Cases of fixed drug eruption have been reported with meloxicam use. Meloxicam should not be re-administered to patients with a history of fixed drug eruption associated with meloxicam. Cross-reactivity with other oxicams is possible.

Anaphylactoid reactions. As with other NSAIDs, anaphylactoid reactions may occur in patients without known sensitivity to meloxicam.

Meloxicam should also not be used in patients with aspirin triad. This symptomatic complex occurs in patients with 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. Emergency measures should be taken if anaphylactoid reactions occur. Liver parameters and kidney function. As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, serum bilirubin, or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory parameter abnormalities have been described. These abnormalities were mostly mild and transient. However, if abnormalities are significant or persistent, meloxicam use should be discontinued and follow-up tests performed.

Functional renal failure. Due to the inhibition of the vasodilatory effect of renal prostaglandins, NSAIDs may induce functional renal failure by reducing glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of diuresis and kidney 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, diuretics (see section "Interaction with other medicinal products and other forms of interaction"); 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 Child-Pugh classification).

In isolated cases, NSAID use may lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome. The meloxicam dose for patients with end-stage renal failure on dialysis should not exceed 7.5 mg. Dose adjustment 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 affect the natriuretic effects of diuretics. Additionally, a reduction in the antihypertensive effect of antihypertensive drugs may occur (see section "Interaction with other medicinal products and other forms of interaction"). As a result, edema, heart failure, or arterial hypertension may be accelerated or exacerbated in sensitive patients. Therefore, clinical monitoring is recommended for patients at risk of sodium, potassium, and water retention (see sections "Contraindications" and "Dosage and administration").

Hyperkalemia. Hyperkalemia may be caused by diabetes mellitus or concomitant use of drugs that increase potassium levels (see section "Interaction with other medicinal products and other forms of interaction"). In such cases, potassium levels should be monitored regularly.

Combination with pemetrexed. In patients with mild to moderate renal impairment receiving pemetrexed, meloxicam treatment should be suspended at least 5 days before pemetrexed administration, on the day of administration, and for at least 2 days after administration (see section "Interaction with other medicinal products and other forms of interaction").

Other warnings and safety measures. Adverse reactions are often less 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 kidney, liver, and heart function is more likely. Elderly patients have a higher frequency of adverse reactions during NSAID treatment, especially gastrointestinal bleeding and perforation, which can be fatal (see section "Dosage and administration").

Meloxicam, like any other NSAID, may mask symptoms of infectious diseases. As with intramuscular administration of other NSAIDs, abscess or necrosis may occur at the injection site. Meloxicam may negatively affect reproductive function and is therefore not recommended for women wishing to become pregnant. For women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam should be considered (see section "Use during pregnancy or breastfeeding").

Masking of inflammation and fever. The pharmacological action of meloxicam aimed at reducing fever and inflammation may complicate the diagnosis of suspected non-infectious painful conditions.

Treatment with corticosteroids. Meloxicam cannot be a likely substitute for corticosteroids in the treatment of corticosteroid deficiency.

Hematological effects. Anemia is possible in patients receiving NSAIDs, particularly meloxicam. This may be related to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or incompletely described effects on erythropoiesis. In patients receiving long-term NSAID treatment, particularly meloxicam, hemoglobin or hematocrit levels should be monitored if symptoms and signs of anemia are present. NSAIDs inhibit platelet aggregation and may lead to prolonged bleeding time in some patients. Unlike acetylsalicylic acid, their effect on platelet function is quantitatively less, short-term, and reversible. Careful monitoring is required for patients prescribed meloxicam who may have adverse effects on platelet function, such as coagulation disorders, and patients receiving anticoagulants. Use in patients with asthma. Patients with asthma may have aspirin-induced asthma. Use of acetylsalicylic acid in patients with aspirin-induced 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 and should be used cautiously in patients with existing asthma.

Important information on excipients. The medicinal product contains less than 1 mmol of sodium (23 mg) per 1.5 mL ampoule, i.e., is essentially sodium-free.

Use during pregnancy or breastfeeding

Pregnancy.

Inhibition of prostaglandin synthesis may negatively 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 heart defects increased from less than 1% to about 1.5%. This risk is believed to increase with higher doses and longer duration of treatment. In animal studies, administration of a prostaglandin synthesis inhibitor led to increased pre- and post-implantation losses and embryofetal mortality. Furthermore, in animals receiving a prostaglandin synthesis inhibitor during organogenesis, the frequency of various developmental abnormalities, including cardiovascular ones, was increased.

From the 20th week of pregnancy, use of meloxicam may cause oligohydramnios due to fetal kidney dysfunction. Oligohydramnios may occur soon after starting treatment and is usually reversible after discontinuation of treatment. Therefore, the medicinal product should not be used during the first and second trimesters of pregnancy, except in cases of urgent need. If meloxicam is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dosage and duration of treatment should be minimal. Prenatal monitoring for oligohydramnios and constriction of the arterial duct after meloxicam exposure is recommended for several days starting from the 20th week of pregnancy. If oligohydramnios or constriction of the arterial duct is detected, meloxicam use should be discontinued.

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

• ·cardiopulmonary toxicity (with premature constriction/closure of the arterial duct and pulmonary hypertension);
• ·kidney dysfunction (see above);

risks in late pregnancy for mother and newborn:

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

Therefore, the medicinal product is contraindicated during the third trimester of pregnancy.

Breastfeeding period.

Although specific data on meloxicam are lacking, it is known that NSAIDs can pass into breast milk. Therefore, use of the medicinal product is not recommended for breastfeeding women.

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 use should be considered.

Ability to affect reaction speed when driving or operating machinery

No specific studies on the effect of the medicinal product on the ability to drive or operate machinery have been conducted. Given the pharmacodynamic profile and observed adverse reactions, meloxicam is not expected to affect or may have 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

Intramuscular use. One injection of 15 mg once daily.

DO NOT EXCEED THE DOSE OF 15 mg/DAY.

Treatment should be limited to one injection at the beginning of therapy, with a maximum duration of up to 2–3 days only in justified exceptional cases (e.g., when oral and rectal routes of administration are not feasible). Adverse reactions can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to control symptoms (see section "Special precautions for use"). The patient's need for symptomatic relief and response to treatment should be periodically evaluated.

Elderly patients (see section "Pharmacokinetics"). The recommended dose for elderly patients is 7.5 mg daily (half of a 1.5 ml vial) (see subsection "Patients at increased risk of adverse reactions" below and section "Special precautions for use").

Patients at increased risk of adverse reactions (see section "Special precautions for use"). For patients at increased risk of adverse reactions, e.g., patients with a history of gastrointestinal disorders or risk factors for cardiovascular diseases, treatment should be initiated at a dose of 7.5 mg daily (half of a 1.5 ml vial).

Renal impairment. This medicinal product is contraindicated in patients with severe renal impairment who are not on haemodialysis (see section "Contraindications"). For patients with end-stage renal disease on haemodialysis, the dose should not exceed 7.5 mg daily (half of a 1.5 ml vial). Dose reduction is not required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 ml/min).

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

Method of administration.

For intramuscular use.

The medicinal product MELOXICAM-VISTA, solution for injection, is administered by deep intramuscular injection into the upper outer quadrant of the buttock, strictly observing aseptic technique. In case of repeated administration, it is recommended to alternate between left and right buttocks. Before injection, it is important to ensure that the needle tip is not within a blood vessel. The injection should be stopped immediately if severe pain occurs during administration. If the patient has a hip prosthesis, the injection should be administered into the opposite buttock. For continuation of treatment, oral formulations of the drug (tablets) should be used.

Children

The medicinal product is contraindicated in patients under 18 years of age (see section "Contraindications").

Overdose

Symptoms. 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 arterial 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.

Treatment. In case of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown accelerated elimination of meloxicam using 4 oral doses of cholestyramine administered 3 times daily.

Adverse Reactions

Data from studies and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and during prolonged treatment) is associated with a certain increased risk of thrombotic events (such as myocardial infarction or stroke) (see section "Special Warnings and Precautions for Use"). 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 (see section "Special Warnings and Precautions for Use"). Following administration of the medicinal product, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been observed (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently. Serious skin reactions have been reported, including Stevens–Johnson syndrome and toxic epidermal necrolysis (see section "Special Warnings and Precautions for Use").

The frequency of the adverse reactions listed below is based on reported adverse reactions recorded in 27 clinical trials with treatment duration of at least 14 days. The information is based on clinical trials involving 15,197 patients who received oral meloxicam at daily doses of 7.5 mg or 15 mg for up to one year.

Also included are adverse reactions identified from post-marketing experience.

Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders: uncommon — anemia; rare — blood test abnormalities (including changes in leukocyte count), leukopenia, thrombocytopenia. Very rare cases of agranulocytosis have been reported (see "Specific serious and/or common adverse reactions" below).

Immune system disorders: uncommon — allergic reactions, excluding anaphylactic or anaphylactoid reactions; frequency not known — anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, including shock.

Psychiatric disorders: rare — mood changes, night terrors; frequency not known — confusion, disorientation, insomnia.

Nervous system disorders: common — headache; uncommon — dizziness, somnolence.

Eye disorders: rare — visual disturbances including blurred vision; conjunctivitis.

Ear and labyrinth disorders: uncommon — vertigo; rare — tinnitus.

Cardiac disorders: rare — palpitations.

Heart failure associated with NSAID use has been reported.

Vascular disorders: uncommon — increased blood pressure (see section "Special Warnings and Precautions for Use"), flushing.

Respiratory, thoracic and mediastinal disorders: rare — asthma in patients with a history of allergy to acetylsalicylic acid and other NSAIDs; frequency not known — upper respiratory tract infections, cough.

Gastrointestinal disorders: very common — dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; uncommon — occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, eructation; rare — colitis, gastroduodenal ulcer, esophagitis; very rare — gastrointestinal perforation; frequency not known — pancreatitis.

Gastrointestinal bleeding, ulcers, or perforation may be severe and potentially fatal, particularly in elderly patients (see section "Special Warnings and Precautions for Use").

Hepatobiliary disorders: uncommon — liver function test abnormalities (e.g., elevated transaminases or bilirubin); rare — hepatitis; frequency not known — jaundice, hepatic failure.

Skin and subcutaneous tissue disorders: uncommon — angioedema, pruritus, rash; rare — Stevens–Johnson syndrome, toxic epidermal necrolysis, urticaria; very rare — bullous dermatitis, erythema multiforme; frequency not known — photosensitivity reactions, exfoliative dermatitis, fixed drug eruption (see section "Special Warnings and Precautions for Use").

Renal and urinary disorders: uncommon — sodium and water retention, hyperkalemia (see sections "Interaction with Other Medicinal Products and Other Forms of Interaction" and "Special Warnings and Precautions for Use"), changes in renal function parameters (increased serum creatinine and/or urea); rare — acute renal failure, particularly in patients with risk factors (see section "Special Warnings and Precautions for Use"); frequency not known — urinary tract infections, micturition disorders.

Reproductive system and breast disorders: frequency not known — female infertility, delayed ovulation.

General disorders and administration site conditions: common — injection site induration, injection site pain; uncommon — edema, including peripheral edema; frequency not known — influenza-like symptoms.

Musculoskeletal and connective tissue disorders: frequency not known — arthralgia, back pain, signs and symptoms related to joints.

Specific serious and/or common adverse reactions. Very rare cases of agranulocytosis have been reported in patients receiving meloxicam and other potentially myelotoxic medicinal products (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Adverse reactions not associated with the use of the medicinal product but typical for other compounds of the class. Organic kidney 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 (see section "Special Warnings and Precautions for Use").

Reporting of suspected adverse reactions. Reporting suspected adverse reactions after marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life. 5 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 30 °C. Keep out of the reach and sight of children.

Packaging. 1.5 ml (15 mg) in ampoules, 5 ampoules per cassette in a carton.

Prescription status. Prescription only.

Manufacturer. HELP S.A.

Manufacturer's address and place of business. Pedi n’Ionninon, Ioannina, 45500, Greece