INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MELOXIC (MELOXIC)

Composition:

Active ingredient: meloxicam;

1.5 ml of the preparation contains 15 mg of meloxicam;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: solution ranging from yellow to yellowish-green, clear, with a characteristic odor.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.

ATC code M01AC06.

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 demonstrates 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 reaches approximately 1.6–1.8 mcg/mL and is achieved within 1–6 hours.

Distribution. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%). It 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 ranging from 7% to 20%. The volume of distribution after multiple oral doses of meloxicam (7.5 mg 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, 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. Elimination of meloxicam occurs primarily as metabolites in equal proportions in 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 after both 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 had significantly higher total clearance. Reduced plasma protein binding has been observed in patients with end-stage renal disease. In end-stage renal disease, increased volume of distribution may lead to higher free meloxicam concentrations. The daily dose should not exceed 7.5 mg (see section "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.

Clinical characteristics.

Indications.

Meloxicam, solution for injection, is indicated for short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when other routes of administration are not applicable.

Meloxicam, solution for injection, is indicated for use in adults.

Contraindications.

Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
age under 18 years;
hypersensitivity to meloxicam or to any of the excipients of the medicinal product, or to other active substances with similar action, such as NSAIDs, acetylsalicylic acid; meloxicam should not be administered to patients who have experienced asthma symptoms, 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;
bleeding disorders or concomitant use of anticoagulants (contraindications related to the route of administration);
severe heart failure;
treatment of perioperative pain in coronary artery bypass grafting (CABG).

Interaction with other medicinal products and other forms of interaction.

Interaction studies were conducted only in adults.

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 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 NSAIDs and acetylsalicylic acid ≥ 3 g per day. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), acetylsalicylic acid in anti-inflammatory 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 bleeding or gastrointestinal 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 solution for injection is contraindicated in patients undergoing anticoagulant therapy (see section "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 gastrointestinal 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 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 drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, combination therapy should be used with caution, especially in elderly patients. Adequate hydration should be ensured, and renal function should be monitored after initiation of combination therapy and periodically thereafter (see section "Special precautions for use").

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

Calcineurin inhibitors (e.g., cyclosporine, tacrolimus). 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 on NSAIDs increasing plasma lithium concentrations (by reducing renal excretion of lithium) are available, 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 (>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 count and renal function should be monitored. Caution is advised when NSAID and methotrexate are taken consecutively for 3 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 ml/min to 79 ml/min), meloxicam should be withheld for 5 days before pemetrexed administration, on the day of administration, and for 2 days after administration. 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 15 mg dose of 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 and partially CYP 3A4) and one-third via other pathways, e.g., peroxidative 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 combining meloxicam with medicinal products such as oral antidiabetics (sulfonylurea derivatives, nateglinide); such interactions may lead to increased plasma levels of these drugs 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 when the medicinal product was taken concomitantly with antacids, cimetidine, or digoxin.

Children

Interaction studies were 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 there is insufficient therapeutic effect, and additional NSAIDs should not be used, as this may increase toxicity without proven therapeutic benefits. Concomitant use of meloxicam with other 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.

Particular attention should be paid to a history of esophagitis, gastritis, and/or peptic ulcer to ensure their complete treatment before initiating meloxicam therapy. Close monitoring for possible recurrence is required in patients being 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 prior symptoms or serious gastrointestinal disease history.

The risk of gastrointestinal bleeding, ulceration, or perforation is higher with increasing doses of meloxicam, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should start treatment with the lowest effective dose. For these patients, 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 acetylsalicylic acid or other drugs increasing 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 during the initial stages of treatment.

Concomitant use of meloxicam is not recommended in patients receiving 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 NSAIDs, 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.

The drug should be used with caution in patients with gastrointestinal disorders in their history (ulcerative colitis, Crohn's disease), as these conditions may worsen (see section "Adverse reactions").

Hepatic disorders

Up to 15% of patients treated with meloxicam may experience increased values of one or more liver function tests. Such laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Significant increases in ALT or AST (approximately three 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 outcomes, have been reported during clinical trials with NSAIDs.

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

Cardiovascular disorders

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

Patients with risk factors should undergo 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 the use of certain NSAIDs (particularly at high doses and during prolonged treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There is insufficient data to exclude such risk for meloxicam.

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

Use of meloxicam may increase the risk of serious cardiovascular thrombotic complications, myocardial infarction, and stroke, which may be fatal. The increased risk is associated with the duration of use. Patients with cardiovascular diseases 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 the signs and symptoms of severe skin reactions and closely monitored for skin reactions. The highest risk of developing 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. Early diagnosis and discontinuation are associated with a better prognosis in severe skin reactions. If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking meloxicam, the drug must not be restarted at any time in the future.

Cases of fixed drug eruption (FDE) have been reported with meloxicam use. Meloxicam should not be re-administered to patients with a history of FDE associated with meloxicam. Potential cross-reactivity may occur with other oxicams.

Anaphylactic reactions

As with other NSAIDs, anaphylactic reactions may occur in patients without a known reaction to meloxicam. The drug 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 experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Immediate measures should be taken if an anaphylactic reaction is detected.

Liver parameters and kidney function

As with treatment with most NSAIDs, isolated cases of increased serum transaminase levels, serum bilirubin, or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory parameter deviations have been described. In most cases, these deviations were minor and transient. If significant or persistent deviations are confirmed, meloxicam should be discontinued and follow-up tests conducted.

Renal functional impairment

NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, may induce renal functional impairment by reducing glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of diuresis and kidney function at the beginning of treatment or after dose increase is recommended 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 impairment;
nephrotic syndrome;
lupus nephritis;
severe hepatic dysfunction (serum albumin < 25 g/L or ≥ 10 according to Child-Pugh classification).

In isolated cases, NSAIDs may lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.

The dose of meloxicam in patients with end-stage renal impairment 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 well tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with treatment with other NSAIDs, caution should be exercised in elderly patients, in whom decreased kidney, liver, and heart function is more likely. Elderly patients have a higher frequency of adverse reactions after NSAID use, 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 therefore not recommended for women wishing to become pregnant. Thus, for women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam should be considered (see section "Use during pregnancy or breastfeeding").

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

Masking of inflammation and fever

The pharmacological action of meloxicam aimed at reducing fever and inflammation may reduce the diagnostic value of these signs in identifying complications related to suspected non-infectious painful conditions.

Corticosteroid therapy

Meloxicam cannot be considered a suitable substitute for corticosteroids in the treatment of corticosteroid deficiency.

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 receiving long-term meloxicam treatment 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 acetylsalicylic acid, their effect on platelet function is quantitatively smaller, short-term, and reversible. Careful monitoring is required in patients receiving meloxicam who may have adverse reactions related to changes in platelet function, such as coagulation disorders, or patients receiving anticoagulants.

Use in patients with asthma

Patients with asthma may have aspirin-sensitive asthma. Use of acetylsalicylic acid 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 and should be used with caution in patients with asthma.

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 heart defects increased from less than 1% to approximately 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, an increased frequency of various developmental abnormalities, including cardiovascular, has been reported.

From the 20th week of pregnancy, use of meloxicam injection solution may cause oligohydramnios due to fetal kidney dysfunction. Kidney dysfunction may occur almost immediately after starting treatment and is usually reversible after discontinuation of meloxicam. Additionally, arterial duct constriction has been reported after treatment in the second trimester, which resolved after discontinuation of treatment.

Antenatal monitoring for oligohydramnios and arterial duct constriction may be appropriate after meloxicam use for several days starting from the 20th week of pregnancy. Meloxicam should be discontinued if signs of oligohydramnios or arterial duct constriction are detected.

During the first and second trimesters of pregnancy, meloxicam should not be used except in cases of urgent need. If a woman is trying to become pregnant or uses meloxicam during the first and second trimesters of pregnancy, dosing and duration of treatment should be minimized.

In 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 function impairment, which may progress to renal failure with oligohydramnios (see above);

possible risks in late pregnancy for mother and newborn:

potential for 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 in the third trimester of pregnancy.

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

Fertility. Meloxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, 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.

Ability to affect reaction speed when driving or operating machinery.

No specific studies on the effect of the drug on the ability to drive or operate machinery have been conducted. However, based on the pharmacodynamic profile and observed adverse reactions, meloxicam has no effect or a negligible 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.

Dosing

One injection of 15 mg once daily.

DO NOT EXCEED THE DOSE OF 15 MG/DAY.

Treatment should be limited to a single injection at the beginning of therapy; maximum duration of treatment – up to 2–3 days 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 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 periodically evaluated.

Special Patient Populations

Elderly patients and patients at increased risk of adverse reactions

The recommended dose for elderly patients is 7.5 mg per day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg per day (half of a 1.5 ml vial) (see section "Special Warnings and Precautions for Use").

Renal impairment

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).

Dosage adjustment is not required in patients with moderate to moderate renal impairment (patients with creatinine clearance above 25 ml/min). For patients with severe renal impairment not undergoing dialysis, see section "Contraindications".

Hepatic impairment

Dosage adjustment 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 drug should be administered slowly by deep intramuscular injection into the upper outer quadrant of the buttock, strictly following aseptic techniques. When repeated administration is necessary, it is recommended to alternate injection sites (left and right buttocks). Prior to injection, it is important to ensure that the needle tip is not within a blood vessel.

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

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

Children.

Meloxik, 15 mg/1.5 ml solution for injection, 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 treatment. Gastrointestinal bleeding may occur. Severe poisoning may lead to arterial hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, seizures, 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 with 4 oral doses of cholestyramine administered 3 times daily.

Adverse reactions.

Data from studies and epidemiological data suggest that the use of certain NSAIDs (particularly 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 precautions for use").

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

Most of the adverse reactions observed are of gastrointestinal origin. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn's disease have been reported after administration (see section "Special 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 precautions for use").

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); 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 "Particular serious and/or common adverse reactions").

Immune system disorders:

uncommon – allergic reactions other than 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 – 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 precautions for use"), flushing.

Respiratory, thoracic and mediastinal disorders:

rare – asthma in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs;

frequency not known – upper respiratory tract infections, cough.

Gastrointestinal disorders:

common – dyspepsia, nausea, vomiting, abdominal pain, diarrhea;

uncommon – occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, constipation, flatulence, 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, especially in elderly patients (see section "Special precautions for use").

Hepatobiliary disorders:

uncommon – liver function test abnormalities (e.g., increased transaminases or bilirubin);

very 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.

Renal and urinary disorders:

uncommon – sodium and water retention, hyperkalemia (see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction"), changes in renal function parameters (increased creatinine and/or blood urea);

very rare – acute renal failure, particularly in patients with risk factors (see section "Special precautions for use");

frequency not known – urinary tract infections, disturbances in micturition frequency.

General disorders and administration site conditions:

common – induration at injection site, pain at injection site;

uncommon – edema, including peripheral edema;

frequency not known – influenza-like symptoms.

Reproductive system and breast disorders:

frequency not known – female infertility, ovulation delay.

Musculoskeletal and connective tissue disorders:

frequency not known – arthralgia, back pain, signs and symptoms related to joints.

Particular serious and/or common adverse reactions

Very rare cases of agranulocytosis have been reported in patients taking 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 generally 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 precautions for use").

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging to protect from light.

Keep out of reach of children.

Incompatibilities.

Meloxicam solution for injection should not be mixed in the same syringe with other medicinal products.

Packaging.

Clear glass ampoules with a capacity of 2 ml (each ampoule contains 1.5 ml of solution for injection).

3 or 5 ampoules per cardboard box.

Prescription status.

Prescription only.

Manufacturer. Pharmaceutical Works «Polpharma» S.A., Poland.

Manufacturer's address and place of business.

19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.