MOVICSICAM®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOVIKSIKAM® (MOVIXICAM®)

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 yellow solution with a greenish tint, practically free from extraneous particles.

Pharmacotherapeutic group.

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

Pharmacological properties.

Pharmacodynamics.

Movixicam® is a non-steroidal anti-inflammatory drug (NSAID) from the oxicam group, possessing anti-inflammatory, analgesic, and antipyretic properties.

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 administration. The relative bioavailability compared to oral administration is nearly 100%. Therefore, dose adjustment when switching from intramuscular to oral administration is not required. One hour after intramuscular administration of 15 mg meloxicam, the maximum plasma concentration was 1.62 \µg/mL.

Distribution. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%). Meloxicam penetrates into synovial fluid, where its concentration reaches approximately half of the plasma concentration. The volume of distribution is low, averaging 11 L. Individual variations are approximately 7–20%.

Biotransformation. Meloxicam is metabolized by liver enzymes. Four different metabolites of meloxicam, pharmacodynamically inactive, have been identified in urine. The main metabolite, 5’-carboxymeloxicam (60%), is formed via oxidation of the intermediate metabolite 5’-hydroxymethylmeloxicam. The amount of unchanged excreted 5’-hydroxymethylmeloxicam is 9%. In vitro studies have shown that CYP 2C9 plays a major role in this metabolic pathway, with a minor contribution from the CYP 3A4 isoenzyme. Peroxidase activity is likely involved in the formation of two other metabolites, accounting for 16% and 4% of the administered dose, respectively.

Elimination. Meloxicam is primarily eliminated in the form of 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 mean elimination half-life is approximately 20 hours. Total plasma clearance averages 8 mL/min.

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

Special patient groups.

Patients with hepatic/renal impairment. Mild to moderate hepatic or renal impairment does not significantly affect the pharmacokinetics of meloxicam. Patients with moderate renal impairment showed 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 concentrations of free meloxicam (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, 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.

Contraindications.

• Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
• pediatric age under 18 years;
• hypersensitivity to meloxicam, to other components of the medicinal product, or to active substances with similar actions, such as NSAIDs, acetylsalicylic acid; meloxicam should not be administered to patients who experience 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/hemorrhage in medical history (two or more separate confirmed episodes of ulcer or bleeding);
• severe hepatic insufficiency;
• severe renal insufficiency without dialysis;
• gastrointestinal bleeding, cerebrovascular hemorrhage in medical history, or other coagulation disorders;
• hemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration);
• severe heart failure;
• treatment of perioperative pain associated with 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 (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 NSAIDs and acetylsalicylic acid ≥ 3 g/dose. 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 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 (see section "Special precautions for use"). Intramuscular injection of meloxicam solution for injection is contraindicated in patients undergoing anticoagulant therapy (see sections "Contraindications" and "Special precautions for use").

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

Thrombolytics and antiplatelet agents. Increased risk of bleeding due to inhibition of platelet function and damage to the gastroduodenal mucosa.

Selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding.

Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive 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 acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should receive adequate hydration, 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 indicate that NSAIDs increase 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 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 taking high-dose methotrexate (more than 15 mg/week) (see section "Special precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered in patients taking low-dose methotrexate, including those with impaired renal function. If combination therapy is necessary, blood parameters and renal function should be monitored. Caution is advised if NSAID and methotrexate administration lasts for 3 consecutive days, as plasma methotrexate levels may rise and increase toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, hematological toxicity of methotrexate may increase with NSAID therapy (see above) (see section "Adverse reactions").

Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with creatinine clearance between 45 and 79 ml/min, meloxicam administration should be suspended 5 days before, on the day of, and 2 days after pemetrexed infusion. 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).

For 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 concurrently 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 meloxicam elimination by disrupting enterohepatic circulation, thus increasing meloxicam clearance by 50% and reducing its half-life to 13±3 hours. This interaction is clinically significant.

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

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

Oral antidiabetic agents (sulfonylureas, 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 in combination with medicinal products such as oral antidiabetic agents (sulfonylureas, 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 the development of hypoglycemia.

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 inadequate, and additional NSAIDs should not be used concomitantly, as this may increase toxicity without providing additional therapeutic benefit. Concomitant use of meloxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Meloxicam is not indicated for the treatment of patients requiring relief of acute pain.

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

Particular attention should be paid to a history of oesophagitis, gastritis and/or peptic ulcer to ensure complete treatment prior to initiating meloxicam therapy. Close monitoring for possible recurrence is required in patients previously 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, regardless of prior symptoms or serious gastrointestinal conditions in 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 be initiated on the lowest effective dose. For these patients, concomitant use of protective agents (such as misoprostol or proton pump inhibitors) should be considered. This also applies to patients requiring concomitant use of low-dose acetylsalicylic acid 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, particularly elderly patients, should be informed about any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during initial stages of treatment.

Use of meloxicam is not recommended in patients receiving concomitant 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, 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 gastrointestinal diseases in history (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").

Hepatic disorders

In patients receiving NSAIDs (including meloxicam), elevation of one or more liver function tests may occur. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Increases in alanine aminotransferase or aspartate aminotransferase (approximately 3 times or more above normal) may occur. Rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, hepatic necrosis, and hepatic failure, some with fatal outcome, have been reported.

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

Cardiovascular disorders

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

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

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and during prolonged treatment) may slightly increase the risk of thrombotic vascular events (e.g., myocardial infarction or stroke). There are insufficient data to exclude such risk for meloxicam.

Therapy with meloxicam should be initiated only after careful consideration in patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. A similar assessment is required before initiating long-term treatment in patients with cardiovascular risk factors (such as hypertension, hyperlipidaemia, diabetes mellitus, smoking).

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 risk factors for cardiovascular disease have an increased risk of thrombotic complications.

Skin disorders

Serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been observed very rarely with NSAIDs (see section "Adverse reactions"). The highest risk of such reactions occurs early in treatment, with most cases appearing within the first month of therapy. At the first appearance of signs of severe skin reactions (e.g., progressive skin rash often with blisters or mucosal lesions) or other signs of hypersensitivity, meloxicam should be discontinued. Prompt diagnosis of skin disorders and discontinuation of any drug that may cause severe skin reactions are crucial, as this is associated with a better prognosis in severe skin reactions. If exfoliative dermatitis, Stevens-Johnson syndrome, or toxic epidermal necrolysis has occurred during meloxicam use, re-administration of the drug is contraindicated.

Cases of fixed drug eruption have been reported with meloxicam. Meloxicam should not be re-administered to patients with 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 hypersensitivity to meloxicam. The drug should not be used in patients with aspirin triad. This symptomatic complex occurs in patients with bronchial asthma who have rhinitis, with or without nasal polyps, or who have experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Immediate emergency measures should be taken if an anaphylactoid 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, as well as increased serum creatinine, blood urea nitrogen, and other laboratory abnormalities have been reported. In most cases, these abnormalities were mild and transient. If significant or persistent abnormalities are confirmed, meloxicam should be discontinued and follow-up tests performed.

Functional renal impairment

NSAIDs, by inhibiting the vasodilatory effect of renal prostaglandins, may induce functional renal impairment due to decreased 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 impairment;
• nephrotic syndrome;
• lupus nephritis;
• severe hepatic dysfunction (serum albumin <25 g/L or ≥10 according to Child-Pugh classification).

In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal medullary 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 sodium, potassium, and water retention and may interfere with 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"). Consequently, oedema, heart failure, or hypertension may be accelerated or exacerbated in susceptible patients. Therefore, clinical monitoring is recommended for patients with such risks (see sections "Contraindications" and "Dosage and administration").

Hyperkalaemia

Hyperkalaemia may be caused 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, regular monitoring of potassium levels is required.

Combination with pemetrexed

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

Other warnings and safety measures

Adverse reactions are often poorly tolerated in elderly and debilitated patients, who require careful monitoring. As 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 with NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "Dosage and administration").

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

Meloxicam may impair female fertility and is not recommended for women wishing to become pregnant. Therefore, discontinuation of meloxicam should be considered in women planning pregnancy or undergoing infertility investigations (see section "Use during pregnancy or breastfeeding").

Masking of inflammation and fever

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

Glucocorticoid therapy

Meloxicam cannot be considered a substitute for glucocorticoids in the treatment of glucocorticoid deficiency.

Haematological effects

Anaemia may occur in patients receiving NSAIDs, including meloxicam. This may be related to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or an incompletely described effect on erythropoiesis. Patients undergoing long-term treatment with NSAIDs, including meloxicam, should have haemoglobin or haematocrit monitored if signs of anaemia are present.

NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike acetylsalicylic acid, their effect on platelet function is quantitatively less, short-term, and reversible. Close monitoring is required in patients taking meloxicam who may have adverse effects on platelet function, particularly coagulation disorders, and in patients receiving anticoagulants.

Use in patients with bronchial asthma

Patients with bronchial asthma may have aspirin-sensitive asthma. Administration of acetylsalicylic acid to 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 hypersensitive to acetylsalicylic acid and should be used with caution in patients with bronchial asthma.

Others.

As with other injectable NSAIDs, abscess formation and necrosis may occur at the injection site.

The product contains a very small amount of sodium, i.e., is essentially sodium-free.

Use during pregnancy or breastfeeding.

Fertility.

Meloxicam, like other medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended for women wishing to become pregnant.

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 considered to increase with higher doses and longer duration of treatment.

Use of meloxicam from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation of therapy. In addition, cases of ductus arteriosus constriction have been reported after treatment in the second trimester, most of which resolved after discontinuation. Therefore, meloxicam should not be used during the first and second trimesters of pregnancy, except in cases of extreme necessity. If meloxicam is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose and duration of treatment should be as low as possible.

Ultrasound monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to the drug for several days starting from the 20th gestational week. The drug should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks.

Risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above).

Risks to the mother at the end of pregnancy and to the newborn:

• possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labour.

Therefore, the drug is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding.

Although specific data on meloxicam are lacking, NSAIDs are known to pass into breast milk. Therefore, use of the drug is not recommended in breastfeeding women.

Ability to influence 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. Based on the pharmacodynamic profile and observed adverse reactions, meloxicam is expected to have no effect or 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

Movixicam® should be administered by intramuscular injection.

One injection of 15 mg once daily.

DO NOT EXCEED THE DOSE OF 15 MG PER 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 (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").

Special Patient Populations

Elderly Patients

The recommended dose for elderly patients is 7.5 mg per day (half of a 1.5 ml ampoule).

Patients at Increased Risk of Adverse Reactions

For patients at increased risk of adverse reactions, such as those with a history of gastrointestinal disorders or risk factors for cardiovascular diseases, treatment should be initiated at a dose of 7.5 mg per day (half of a 1.5 ml ampoule).

Renal Impairment

This medicinal product is contraindicated in patients with severe renal impairment who are not undergoing hemodialysis.

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

Dose adjustment is not required in patients with mild 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

Dose 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 observing aseptic technique. In case of repeated administration, the injection site should be alternated (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 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 drug is contraindicated in children (under 18 years of age).

Overdose

Symptoms of acute nonsteroidal anti-inflammatory drug (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.

In case of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown that meloxicam elimination can be accelerated by administering 4 oral doses of cholestyramine 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) may be associated with a small increase in the risk of vascular thrombotic events (such as myocardial infarction or stroke).

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

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

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

Blood and lymphatic system disorders:
Anemia, blood test abnormalities (including changes in white blood cell count), leukopenia, thrombocytopenia. Very rare cases of agranulocytosis have been reported (see description of individual serious and/or common adverse reactions).

Immune system disorders:
Allergic reactions, including anaphylactic shock, anaphylactoid reactions, and anaphylactic reactions.

Psychiatric disorders:
Mood changes, night terrors, confusion, disorientation, insomnia.

Nervous system disorders:
Headache, dizziness, somnolence.

Eye disorders:
Visual disturbances including blurred vision, conjunctivitis.

Ear and labyrinth disorders:
Vertigo, tinnitus.

Cardiovascular disorders:
Palpitations, heart failure, increased blood pressure, flushing.

Respiratory, thoracic and mediastinal disorders:
In patients with a history of allergic reactions to acetylsalicylic acid or other NSAIDs, asthma attacks may occur; upper respiratory tract infections, cough.

Gastrointestinal disorders:
Dyspepsia, nausea, vomiting, abdominal pain, diarrhea, occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, constipation, flatulence, belching, colitis, gastroduodenal ulcer, esophagitis, gastrointestinal perforation, pancreatitis. Gastrointestinal bleeding, ulcers, or perforation may be severe and potentially fatal, particularly in elderly patients.

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

Skin and subcutaneous tissue disorders:
Itching, rash, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, bullous dermatitis, erythema multiforme, photosensitivity, exfoliative dermatitis, fixed drug eruption (see section "Special Warnings and Precautions for Use").

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

Reproductive system and breast disorders:
Female infertility, delayed ovulation.

General disorders and administration site conditions:
Induration at injection site, pain at injection site; edema, including peripheral edema, influenza-like symptoms.

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

Individual serious and/or common adverse reactions.

Very rare cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic medicinal products (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Adverse reactions not observed with this medicinal product but typical for other compounds in the class.

Renal dysfunction up to renal failure: cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging, out of the reach of children, at a temperature not exceeding 25 °C.

Incompatibilities.

The injection solution must not be mixed with other medicinal products in the same syringe.

Packaging.

5 ampoules of 1.5 ml each in a plastic container, in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Help S.A.

Manufacturer's address and place of business.

Pedinion Ianion, Ioannina, 45500, Greece.

Marketing Authorization Holder.

Movi Health GmbH

Address of the Marketing Authorization Holder.

Bleghistrasse 25, 6340 Baar, Switzerland