Meloxicam

INSTRUCTIONS for medical use of the medicinal product MELOXICAM (Meloxicam)

Composition:

Active substance: 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: clear, yellow liquid with a greenish tint.

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

ATC code M01A C06.

Pharmacological properties.

Pharmacodynamics.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, exhibiting anti-inflammatory, analgesic, and antipyretic effects.

Meloxicam demonstrates 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 has been established for all NSAIDs (including meloxicam): inhibition of prostaglandin biosynthesis, which are mediators of inflammation.

Pharmacokinetics.

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

Biotransformation. 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 excreted to a lesser extent (9% of dose).

In vitro studies suggest that CYP 2C9 plays a major role in the metabolic 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 predominantly 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, intravenous, or rectal dose.

Linearity of dose. 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 showed significantly higher total clearance. Reduced plasma protein binding was observed in patients with end-stage renal disease. In end-stage renal disease, increased volume of distribution may lead to increased free meloxicam concentration (see sections "Contraindications" and "Dosage and administration").

Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, the area under the plasma concentration–time curve (AUC) is higher and 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 in pregnancy or lactation");
• 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 actions, such as NSAIDs, acetylsalicylic acid; meloxicam should not be administered to patients who have experienced asthma, nasal polyps, angioedema, or urticaria after taking acetylsalicylic acid or other NSAIDs;
• gastrointestinal bleeding or perforation related to previous NSAID therapy in medical history;
• active or recurrent peptic ulcer/hemorrhage in medical history (two or more separate confirmed episodes of ulcer or bleeding);
• severe hepatic impairment;
• severe renal impairment without dialysis;
• gastrointestinal bleeding, cerebrovascular bleeding in medical history, or other coagulation disorders;
• disorders of hemostasis or concomitant use of anticoagulants (contraindications related to the route of administration);
• severe heart failure.

Do not use for treatment of perioperative pain in coronary artery bypass grafting.

Interaction with other medicinal products and other forms of interactions.

Risks associated with hyperkalemia

Some medicinal products or therapeutic groups may cause hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.

Development of hyperkalemia may depend on the presence of concomitant factors. 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 per day. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), acetylsalicylic acid in 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 development of ulcers in the gastrointestinal tract.

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 meloxicam and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses. Due to intramuscular administration, meloxicam injection solution is contraindicated in patients undergoing anticoagulant therapy (see sections "Contraindications" and "Special precautions for use").

In other cases (e.g., when prophylactic doses are used), caution is required when used concomitantly with heparin due to increased risk of bleeding.

Thrombolytic and antiplatelet medicinal products. 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 effect of diuretics and other antihypertensive medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with impaired renal function), 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, this combination 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., beta-blockers). As with the use of the medicinal products listed below, a reduction in the antihypertensive effect of beta-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. 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 receiving 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 receiving low-dose methotrexate, including patients with impaired renal function. If combination therapy is required, blood parameters and renal function should be monitored. Caution should be exercised when NSAID and methotrexate are taken for 3 consecutive days, as methotrexate plasma levels may increase and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, hematological toxicity of methotrexate may increase during NSAID treatment (see above and section "Adverse reactions").

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

In patients with normal renal function (creatinine clearance ≥ 80 ml/min), a dose of 15 mg meloxicam may reduce pemetrexed elimination and thus increase the frequency of adverse reactions associated with pemetrexed. 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 due to disruption of 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 of which is mediated by cytochrome P450 enzymes (mainly CYP 2C9 and to a lesser extent 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 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 medicinal products and meloxicam. Patients receiving meloxicam and sulfonylurea or nateglinide preparations should be closely monitored for the development of hypoglycemia.

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

Interaction studies were conducted only in adults.

Special precautions for use.

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

If the therapeutic effect is inadequate, the recommended maximum daily dose should not be exceeded. Additional NSAIDs should not be used, as this may increase toxicity without proven therapeutic benefits. Concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Meloxicam should not be used for the treatment of patients requiring relief from acute pain.

If there is no improvement after several days of treatment, the benefit of continued therapy should be re-evaluated.

Patients with a history of esophagitis, gastritis, and/or peptic ulcer should be fully healed before starting meloxicam therapy.

Patients being treated with meloxicam who have such a history should be monitored regularly 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 warning symptoms, or in patients with a history of serious gastrointestinal disorders (see section "Contraindications").

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses and in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, as well as 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 that increase the risk of gastrointestinal adverse reactions (see information below and section "Interaction with other medicinal products and other forms of interaction").

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

Meloxicam is not recommended for patients who are concurrently using 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.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").

Hepatic disorders

Approximately 15% of patients receiving NSAIDs (including meloxicam) may experience elevated levels of one or more liver function tests in serum. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations of ALT or AST (approximately three times or more above normal) were observed in 1% of patients during clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis, and hepatic failure, some of which were fatal, have been reported during clinical trials with NSAIDs.

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

Cardiovascular and cerebrovascular disorders

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

Patients with risk factors should have their blood pressure monitored, particularly at the beginning of meloxicam treatment.

NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk increases with the duration of use. Patients with cardiovascular disease or cardiovascular risk factors may have an increased risk of thrombotic complications. 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, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Such evaluation is also necessary before starting long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smokers).

Skin disorders

Life-threatening severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam use. Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored for skin reactions. The highest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis occurs during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., progressive skin 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. A better prognosis is associated with early diagnosis and discontinuation. 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 have been reported with meloxicam use. Meloxicam should not be re-administered to patients who have 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 sensitivity to meloxicam. Meloxicam should not be used in patients with aspirin triad. This symptomatic complex occurs in patients with asthma who have experienced rhinitis, with or without nasal polyps, or who have experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. 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, increased serum creatinine and 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, due to inhibition of the vasodilatory effect of renal prostaglandins, may induce functional renal impairment by reducing glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of renal function, including urine output, 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 nephropathy;
• severe hepatic dysfunction (serum albumin < 25 g/L or ≥ 10 points on the Child-Pugh classification).

In isolated 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. The dose does not need to be reduced 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. In addition, 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 provoked or exacerbated in susceptible 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, regular monitoring of potassium levels is required.

Combination with pemetrexed

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

Other warnings and safety precautions

Adverse reactions are often less well tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with treatment with other NSAIDs, particular caution should be exercised in elderly patients, in whom reduced renal, hepatic, and cardiac function is more likely. Elderly patients have a higher frequency of adverse reactions caused by 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.

Meloxicam may negatively affect fertility and is not recommended for women who wish 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 action of meloxicam in reducing fever and inflammation may complicate the diagnosis of suspected non-infectious painful conditions.

Treatment with corticosteroids

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

Hematological effects

Anemia may occur in patients receiving NSAIDs, including meloxicam. This may be related to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients on long-term meloxicam therapy 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 less, short-term, and reversible. Patients receiving meloxicam 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 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.

Other

As with intramuscular administration of other NSAIDs, abscess or necrosis may occur at the injection site.

The medicinal product contains less than 1 mmol of sodium (23 mg) per 1.5 mL ampoule, i.e., it is 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 heart defects increased from less than 1% to approximately 1.5%. This risk is considered to increase with increasing dose and duration of treatment.

During the first and second trimesters of pregnancy, meloxicam should not be used except in cases of absolute 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.

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

For the fetus:

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

For the mother and newborn at the end of pregnancy:

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

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

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

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

Ability to affect reaction speed when driving or operating machinery.

There are no specific studies on the effect of the drug on the ability to drive a vehicle or operate machinery. Given the pharmacodynamic profile and adverse reactions of meloxicam, no significant effect on such activities is expected. However, patients who experience visual disturbances, including blurred vision, dizziness, somnolence, vertigo, or other central nervous system disorders, are advised to refrain from driving a vehicle or operating machinery.

Method of Administration and Dosage

Dosing

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; maximum duration up to 2–3 days in justified exceptional cases (i.e., when other routes of administration are not possible). 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 symptom relief and response to treatment should be periodically evaluated.

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 subsection "Patients at Risk of Adverse Reactions" and section "Special Warnings and Precautions for Use").

Patients at 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 on haemodialysis (see section "Contraindications").

For patients with end-stage renal disease on haemodialysis, the dose should not exceed 7.5 mg per day (half of a 1.5 ml vial).

Dose reduction is not required in patients with mild to moderate renal impairment (creatinine clearance >25 ml/min).

Hepatic Impairment

Dose reduction is not required in patients with mild to moderate hepatic impairment.

This medicinal product is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

Method of Administration

For intramuscular use.

The 15 mg/1.5 ml injection solution should be administered by deep intramuscular injection into the upper outer quadrant of the buttock, using strict aseptic technique. In case of repeated administration, the injection site should be alternated (left and right buttock). 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.

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

For continuation of treatment, oral dosage forms (tablets) should be used.

Children

Meloxicam 15 mg/1.5 ml injection solution 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

In case of meloxicam overdose, symptomatic and supportive measures are recommended. Studies have shown enhanced elimination of meloxicam with oral administration of cholestyramine (4 g three times daily).

Adverse Reactions

Data from clinical 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 increased 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.

Gastrointestinal adverse reactions are the most commonly observed. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Following NSAID administration, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn's disease have been reported (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 the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders:

Uncommon – anemia;
Rare – blood test abnormalities (including changes in leukocyte count), leukopenia, thrombocytopenia.

Very rare cases of agranulocytosis have been reported (see "Specific serious and/or common adverse reactions").

Immune system disorders:

Uncommon – allergic reactions, excluding anaphylactic or anaphylactoid reactions;
Frequency not known – anaphylactic shock, anaphylactic reactions, anaphylactoid reactions.

Psychiatric disorders:

Rare – mood changes, night terrors;
Frequency not known – confusion, disorientation, insomnia.

Nervous system disorders:

Common – headache;
Uncommon – dizziness, somnolence.

Eye disorders:

Rare – visual disturbances including blurred vision; conjunctivitis.

Ear and labyrinth disorders:

Uncommon – vertigo;
Rare – tinnitus.

Cardiac disorders:

Rare – palpitations.

Heart failure associated with NSAID use has been reported.

Vascular disorders:

Uncommon – increased blood pressure (see section "Special Warnings and Precautions for Use"), flushing.

Respiratory, thoracic and mediastinal disorders:

Rare – asthma in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs;
Frequency not known – upper respiratory tract infections, cough.

Gastrointestinal disorders:

Very common – gastrointestinal disturbances: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea;
Uncommon – occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, eructation;
Rare – colitis, gastroduodenal ulcer, esophagitis;
Very rare – gastrointestinal perforation;
Frequency not known – pancreatitis.

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

Hepatobiliary disorders:

Uncommon – abnormalities in liver function tests (e.g., increased transaminases or bilirubin);
Very rare – hepatitis;
Frequency 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;
Frequency not known – photosensitivity reactions, exfoliative dermatitis, fixed drug eruption.

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");
Frequency not known – urinary tract infections, disturbances in micturition frequency.

Reproductive system and breast disorders:

Frequency not known – female infertility, ovulation delay.

General disorders and administration site conditions:

Common – injection site induration, injection site pain;
Uncommon – edema, including peripheral edema;
Frequency not known – influenza-like symptoms.

Musculoskeletal and connective tissue disorders:

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

Specific serious and/or common adverse reactions

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

Adverse reactions not associated with the use of this drug but typical of other compounds in the class

Organic renal damage, which may lead to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported (see section "Special Warnings and Precautions for Use").

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

1.5 ml in ampoules; 5 ampoules in a cassette; 1 cassette in a carton.

Prescription status.

Prescription only.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchagovskiy Chemical and Pharmaceutical Plant".

Address of manufacturer and location of its operations.

17 Myru Street, Kyiv, 03134, Ukraine.