INSTRUCTIONS for medical use of the medicinal product ANTEBA (ANTEBA)

Composition:

Active substance: meloxicam;

1 ml of solution contains 10 mg of meloxicam;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, yellowish-green solution.

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

Pharmacological Properties

Pharmacodynamics

ANTEBA is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, possessing anti-inflammatory, analgesic, and antipyretic effects.

The medicinal product has demonstrated high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its exact mechanism of action remains unknown. However, a common mechanism of action exists for all NSAIDs (including meloxicam): inhibition of prostaglandin biosynthesis, which are mediators of inflammation.

Pharmacokinetics

Absorption. Meloxicam is completely absorbed following intramuscular injection. 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, maximum plasma concentration reaches approximately 1.6–1.8 µg/mL and is achieved within 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 variations within 7–20%. The volume of distribution after multiple oral doses of meloxicam (7.5–15 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 have been identified in urine, all of which are pharmacodynamically inactive. 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. Elimination of meloxicam occurs primarily as metabolites in equal proportions via urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, and a negligible amount is excreted in urine. The elimination half-life ranges from 13 to 25 hours, depending on the route of administration (oral, intramuscular, or intravenous). Plasma clearance is approximately 7–12 mL/min after a single oral dose, intravenous, or rectal administration.

Dose linearity. Meloxicam exhibits linear pharmacokinetics 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 failure. In end-stage renal failure, increased volume of distribution may lead to increased concentration of free meloxicam (see sections "Dosage and administration" and "Contraindications").

Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, AUC values are higher and 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.

Short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when other routes of administration cannot be used.

The medicinal product is indicated for treatment of adult patients.

Contraindications.

Third trimester of pregnancy (see section "Use in pregnancy or breastfeeding");
patient age under 18 years;
hypersensitivity to the active substance or to any of the excipients of the medicinal product;
hypersensitivity to active substances with similar action, such as NSAIDs, aspirin. The medicinal product should not be administered to patients who have experienced asthma symptoms, nasal polyps, angioedema, or urticaria after taking aspirin or other NSAIDs;
gastrointestinal bleeding or perforation associated with previous NSAID therapy in medical history;
active or recurrent peptic ulcer / gastrointestinal bleeding in history (two or more separate confirmed episodes of ulcer or bleeding);
severe hepatic impairment;
severe renal impairment without dialysis;
gastrointestinal bleeding, cerebrovascular bleeding in history, or other coagulation disorders;
disorders of hemostasis or concomitant use of anticoagulants (contraindications related to the route of administration);
severe heart failure;
treatment of perioperative pain in coronary artery bypass grafting (CABG).

Interaction with other medicinal products and other types of interactions.

Risks associated with hyperkalemia. Certain medicinal products or therapeutic groups may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (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 whether associated risk factors are present. The risk of hyperkalemia increases if the above-mentioned medicinal products are used concomitantly with meloxicam.

Pharmacodynamic interactions.

Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), as well as acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose.

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

Anticoagulants or heparin. The risk of bleeding is significantly increased due to platelet function inhibition and damage to the gastroduodenal mucosa. NSAIDs may potentiate 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., prophylactic doses), caution is required when using heparin due to increased risk of bleeding.

Thrombolytic and antiplatelet agents. Increased risk of bleeding through 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 medicinal products that inhibit cyclooxygenase 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 (see section "Special precautions for use").

Other antihypertensive medicinal products (e.g., β-blockers). As with the use of the medicinal products listed below, a 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 through mediation of renal prostaglandin effects. 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 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 (by reducing 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 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 (over 15 mg/week) (see section "Special precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low-dose methotrexate, including those with impaired renal function. If combination therapy is required, blood test parameters and renal function should be monitored. Caution should be exercised if NSAID and methotrexate administration continues 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 may increase during NSAID therapy (see above) (see section "Adverse reactions").

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 should be withheld for 5 days before, on the day of, and for 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 <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 accelerates the elimination of meloxicam by disrupting enterohepatic circulation, thus increasing meloxicam clearance by 50% and reducing its 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 enzymes (mainly CYP 2C9, with a minor contribution from 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 in combination with medicinal products such as oral antidiabetic agents (sulfonylurea derivatives, nateglinide); this interaction may lead to increased plasma levels of these agents and meloxicam. Patients receiving meloxicam and sulfonylurea or nateglinide should be closely monitored for signs 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 adult patients.

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 inadequate, 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.

The medicinal product should not be used for the treatment of patients requiring relief of acute pain.

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

Particular attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer to ensure their complete treatment prior to initiating meloxicam therapy. Patients treated with meloxicam and those with such history should be regularly monitored for possible recurrence.

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

The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, especially if complicated with bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should start treatment with the lowest effective dose. Combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered, as well as for patients requiring concomitant use of low-dose aspirin or other medicinal products that increase gastrointestinal risks (see information below 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 in the initial stages of treatment.

Concomitant use of meloxicam is not recommended in patients taking medicinal products that may increase the risk of ulceration or bleeding, such as heparin, as radical therapy or in geriatric practice, anticoagulants such as warfarin or other nonsteroidal anti-inflammatory drugs, or 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 worsen (see section "Adverse reactions").

Hepatic disorders. Up to 15% of patients taking NSAIDs, including meloxicam, may experience elevation of one or more liver function tests. Such 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) 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 liver failure, some with fatal outcome, have been reported during clinical trials with NSAIDs.

Patients with symptoms and/or signs of hepatic dysfunction or with abnormal liver function tests should be evaluated for the development of more severe hepatic failure during therapy. If clinical signs and symptoms are consistent with hepatic disease or if systemic manifestations of disease (e.g., eosinophilia, rash, etc.) occur, the medicinal product should be discontinued.

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

Patients with risk factors should have clinical monitoring of blood pressure at the beginning of therapy, especially at the start of meloxicam treatment.

Data from studies and epidemiological data suggest that use of certain NSAIDs, including meloxicam (particularly at high doses and with prolonged treatment), may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There are insufficient data to exclude such risk for meloxicam.

Meloxicam therapy should be initiated only after careful evaluation in patients with uncontrolled arterial hypertension, congestive heart failure, diagnosed ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. Such evaluation is necessary before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smokers).

NSAIDs may 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 may 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 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 rash often with blisters or mucosal involvement), meloxicam treatment should be discontinued. It is important to diagnose promptly and discontinue any drugs 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 has experienced Stevens-Johnson syndrome or toxic epidermal necrolysis with meloxicam use, 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 who have had a history of fixed drug eruption associated with meloxicam use. Potential cross-reactivity may occur with other oxicams.

Anaphylactic reactions. As with other NSAIDs, anaphylactic reactions may occur in patients without known drug sensitivity. Meloxicam should not be used in patients with aspirin triad. This symptomatic complex occurs in patients with asthma who have reported rhinitis with or without nasal polyps or who have experienced severe, potentially fatal bronchospasm after aspirin or other NSAID use. Emergency measures should be taken if an anaphylactic reaction occurs.

Liver parameters and renal function. As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, serum bilirubin or other liver function parameters, elevated serum creatinine and blood urea nitrogen, as well as other laboratory parameter deviations, have been described. In most cases, these deviations were minor and transient. If significant or persistent deviations are confirmed, meloxicam use should be discontinued and follow-up tests performed.

Functional renal failure. NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, may induce functional renal failure by reducing glomerular filtration. This adverse effect is dose-dependent. Careful 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, 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, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal papillary necrosis or nephrotic syndrome.

The dose of meloxicam in 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 retention of sodium, potassium and water and affect the natriuretic effects of diuretics. In addition, a reduced 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 susceptible patients. Therefore, clinical monitoring is recommended in patients at risk of sodium, potassium and water retention (see sections "Dosage and administration" and "Contraindications").

Hyperkalemia. Hyperkalemia may be promoted by diabetes mellitus or concomitant use of medicinal products 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 interrupted 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 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 frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may 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 use may negatively affect fertility 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 (see section "Use during pregnancy or breastfeeding").

Masking of inflammation and fever. The pharmacological effect aimed at reducing fever and inflammation may reduce the diagnostic value of these signs in identifying complications of a suspected non-infectious painful condition.

Glucocorticoid therapy. Meloxicam cannot be a substitute for glucocorticoids in the treatment of glucocorticoid 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 macroscopic bleeding, or incompletely described effects on erythropoiesis. Patients undergoing long-term NSAID treatment, including meloxicam, should have hemoglobin or hematocrit monitored if symptoms and signs of anemia are present.

NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, transient and reversible. Patients receiving the medicinal product and who may have adverse effects related to changes in platelet function, such as coagulation disorders, or patients receiving anticoagulants, require careful monitoring.

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

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

Use during pregnancy or breastfeeding.

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 defects increased from less than 1% to about 1.5%. This risk is believed to increase with increasing dose and 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, an increased frequency of various developmental abnormalities, including cardiovascular, has been reported.

From the 20th week of pregnancy, use of the medicinal product may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of arterial duct constriction after treatment in the second trimester of pregnancy, which in most cases resolved after discontinuation of treatment. Meloxicam should not be used during the first and second trimesters of pregnancy, except in cases of urgent need. If a woman trying to conceive or pregnant uses meloxicam during the first and second trimesters, the dose and duration of treatment should be as low as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction may be appropriate after drug exposure for several days, starting from the 20th gestational week. The medicinal product should be discontinued if oligohydramnios or arterial duct constriction is detected.

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);
impaired renal function, which may progress to renal failure with oligohydramnios (see above).

Possible risks in late pregnancy for mother and newborn:

prolonged 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 meloxicam are lacking, NSAIDs are known to pass into breast milk. Therefore, use is not recommended for women who are 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 use should be considered.

Ability to influence reaction speed when driving or operating machinery.

No specific studies on the effect of the drug on the ability to drive a vehicle or operate machinery have been conducted. However, based on the pharmacodynamic profile and observed adverse reactions, meloxicam is likely to have no effect or only a minor effect on such activities. Nevertheless, 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 in justified exceptional cases (i.e., when other routes of administration are not feasible). Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use").

The patient’s need for symptomatic relief and response to treatment should be regularly assessed.

Special Patient Categories

Elderly Patients (see section "Pharmacokinetics"). The recommended dose for elderly patients is 7.5 mg per day (half of a 1.5 ml vial) (also see section "Method of Administration and Dosage" – "Patients at Increased Risk of Adverse Reactions" and section "Special Warnings and Precautions for Use").

Patients at Increased Risk of Adverse Reactions (see section "Special Warnings and Precautions for Use"). For patients at increased risk of adverse reactions, e.g., those with a history of gastrointestinal disorders or risk factors for cardiovascular disease, treatment should be initiated at a dose of 7.5 mg per day (half of a 1.5 ml vial).

Renal Impairment. This medicinal product is contraindicated in patients with severe renal impairment who are not undergoing hemodialysis (see section "Contraindications").

For patients with severe renal impairment undergoing dialysis, the dose should not exceed 7.5 mg per day (half of a 1.5 ml vial).

No dose reduction is required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 ml/min).

Hepatic Impairment. No dose reduction is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".

Method of Administration. The product should be administered slowly by deep intramuscular injection into the upper outer quadrant of the buttock, strictly observing aseptic technique. When repeated injections are necessary, it is recommended to alternate between left and right buttocks. Prior to injection, it is important to ensure that the needle tip has not entered a blood vessel.

The injection should be stopped immediately if severe pain occurs during administration.

In patients with a hip prosthesis, the injection should be administered into the opposite buttock.

For continuation of treatment, oral formulations of the drug should be used.

Children

The medicinal product is contraindicated in children (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 care. 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. Symptomatic and supportive measures are recommended for patients with NSAID overdose. Studies have shown that meloxicam elimination is accelerated by administration of 4 oral doses of cholestyramine given 3 times daily.

Adverse Reactions

Data from studies and epidemiological evidence suggest that the use of certain NSAIDs (especially at high doses and during long-term treatment) may be associated with a small increase in the risk of vascular 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 observed adverse effects are gastrointestinal in origin. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn’s disease have been reported following administration (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.

Serious skin reactions have been reported: Stevens-Johnson syndrome and toxic epidermal necrolysis (see section "Special Warnings and Precautions for Use").

Criteria for assessing frequency of adverse drug reactions: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); 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 "Serious and/or Common Adverse Reactions").

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

Psychiatric disorders: rare – mood changes, nightmares; 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 – dizziness; 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 aspirin or other NSAID allergy; not known – upper respiratory tract infections, cough.

Gastrointestinal disorders: very common – gastrointestinal disorders: 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; not known – pancreatitis. Gastrointestinal bleeding, ulcers, or perforation may be severe and potentially fatal, especially in elderly patients (see section "Special Warnings and Precautions for Use").

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

Skin and subcutaneous tissue disorders: uncommon – angioneurotic edema, pruritus, rash; rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria; very rare – bullous dermatitis, erythema multiforme; 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 "Special Warnings and Precautions for Use" and "Interaction with Other Medicinal Products and Other Forms of Interaction"), changes in renal function parameters (increased serum creatinine and/or urea); very rare – acute renal failure, particularly in patients with risk factors (see section "Special Warnings and Precautions for Use"); not known – urinary tract infections, changes in micturition frequency.

Reproductive system and breast disorders: not known – female infertility, ovulation delay.

General disorders and administration site conditions: common – injection site induration, injection site pain; uncommon – edema, including lower limb edema; not known – influenza-like symptoms.

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

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 drug but recognized as 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 suspected adverse reactions. Reporting suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in a place protected from sunlight and inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 1.5 mL in an ampoule; 5 ampoules per blister pack, 1 blister pack per carton.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of business activity.
36 Severina Pototskogo Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.

Anteba