INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALSOKAM (AlSOKAM)

Composition:

Active substance: meloxicam;

1.5 ml of the preparation contains 15 mg of meloxicam;

1 ml of the preparation contains 10 mg of meloxicam;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, yellowish-green solution.

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

ATC code M01A C06.

Pharmacological properties.

Pharmacodynamics.

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

Meloxicam has demonstrated high anti-inflammatory activity in all standard models of inflammation. Its exact mechanism of action remains unknown. However, there is a common mechanism of action shared by all non-steroidal anti-inflammatory drugs (NSAIDs), including meloxicam: inhibition of prostaglandin biosynthesis, which are mediators of inflammation.

Pharmacokinetics.

Absorption. Meloxicam is completely absorbed after intramuscular injection. Its 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 µg/mL and is achieved within 1–6 hours.

Distribution. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%). Meloxicam penetrates into synovial fluid, where its concentration is about half that in plasma. The volume of distribution is low, averaging 11 L after intramuscular or intravenous administration, with individual variations within 7–20%. The volume of distribution after multiple oral doses of meloxicam (7.5 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 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. Meloxicam is excreted mainly 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 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 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, average 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. The average plasma clearance at steady state in elderly patients was slightly lower than in young volunteers (see section "Dosage and administration").

Clinical characteristics.

Indications.

For short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when other routes of administration cannot be used. Alsykam, solution for injection, is indicated for treatment of adults.

Contraindications.

Third trimester of pregnancy (see section "Use in pregnancy or breastfeeding");
patient age under 18 years;
hypersensitivity to the active substance or to any of the excipients of the medicinal product;
hypersensitivity to active substances with similar action, such as NSAIDs, 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 insufficiency;
severe renal insufficiency without dialysis;
gastrointestinal bleeding, cerebrovascular bleeding in medical history or other coagulation disorders;
haemostasis 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.

Interaction with other medicinal products and other forms of interaction.

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

The onset of hyperkalemia may depend on whether associated factors are present. The risk of hyperkalemia increases if the above-mentioned medicinal products are used concomitantly with meloxicam.

Pharmacodynamic interactions

Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/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 gastrointestinal bleeding or ulceration.

Anticoagulants or heparin. The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use"). Concomitant use of NSAIDs and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses. Due to intramuscular administration, meloxicam injection solution is contraindicated in patients undergoing anticoagulant therapy (see sections "Contraindications" and "Special precautions for use"). In other cases (e.g., prophylactic doses), caution is required when using heparin due to increased risk of bleeding.

Thrombolytic 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 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, combination therapy should be used with caution, especially in elderly patients. Patients should receive adequate hydration, and renal function should be monitored after initiation of combination therapy and periodically thereafter (see section "Special precautions for use").

Other antihypertensive medicinal products (e.g., β-blockers). Possible reduction in antihypertensive effect of β-blockers (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 effects on renal prostaglandins. Renal function should be monitored during treatment. Careful monitoring of renal function is recommended, especially in elderly patients.

Deferasirox. Concomitant use of meloxicam and deferasirox increases the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these medicinal products.

Pharmacokinetic interaction: effect of meloxicam on the pharmacokinetics of other medicinal products

Lithium. Data exist on NSAIDs increasing plasma lithium concentrations (by reducing renal excretion of lithium), which may reach toxic levels. Concomitant use of lithium and NSAIDs is not recommended (see section "Special precautions for use"). If combination therapy is necessary, plasma lithium levels should be closely monitored at the 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 (over 15 mg/week) (see section "Special precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered when prescribing to patients taking low-dose methotrexate, including patients with impaired renal function. If combination therapy is required, blood parameters and renal function must be monitored. Caution should be exercised if NSAID and methotrexate are taken for 3 consecutive days, as plasma levels of methotrexate 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 between 45 and 79 ml/min, meloxicam administration should be suspended 5 days before, on the day of, and 2 days after pemetrexed administration. If combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, especially for signs of myelosuppression and gastrointestinal adverse reactions. Concomitant use of meloxicam with pemetrexed is not recommended in patients with severe renal insufficiency (creatinine clearance < 45 ml/min).

In patients with normal renal function (creatinine clearance ≥ 80 ml/min), 15 mg doses of meloxicam may reduce pemetrexed elimination and thus increase the frequency of pemetrexed-related adverse reactions. Therefore, 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 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.

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 (CYP) P450 enzymes (mainly CYP 2C9 and minor CYP 3A4 pathways), 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 clearly 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 antidiabetics (sulfonylurea derivatives, nateglinide); this interaction may lead to increased plasma levels of these medicinal products and meloxicam. Patients receiving meloxicam and sulfonylurea or nateglinide should be closely monitored for development of hypoglycemia.

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

Children. Interaction studies have been conducted only in adults.

Special precautions for use.

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

The recommended maximum daily dose should not be exceeded if the therapeutic effect is inadequate, and additional NSAIDs should not be used, as this may increase toxicity without proven therapeutic benefits. Concomitant use of meloxicam with 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 complete treatment prior to initiating meloxicam therapy. Patients treated with meloxicam and those with such history should be regularly monitored for possible recurrence.

Gastrointestinal disorders

As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, regardless of prior symptoms or history of serious gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation is greater 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. Such patients should be started on the lowest effective dose. For these patients, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that increase gastrointestinal risks, combination therapy with protective agents such as misoprostol or proton pump inhibitors may be required (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 report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

Use of meloxicam is not recommended in patients who are concurrently using medicinal products that increase the risk of ulceration or bleeding, such as heparin, anticoagulants (including warfarin), 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

Elevations in one or more liver function tests may occur in up to 15% of patients receiving NSAIDs (including meloxicam). These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (approximately three times or more above the upper limit of normal) were observed in 1% of patients during clinical trials with NSAIDs. Additionally, rare cases of severe hepatic reactions, including jaundice, fulminant fatal hepatitis, hepatic necrosis, and hepatic failure, some with fatal outcomes, have been reported during clinical trials with NSAIDs.

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

Cardiovascular and cerebrovascular disorders

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure should be closely monitored, as fluid retention and edema have been observed during NSAID therapy.

Patients with cardiovascular risk factors should have blood pressure clinically monitored at the start of therapy, particularly at the beginning of meloxicam treatment.

Clinical trial data and epidemiological evidence suggest that use of certain NSAIDs (particularly at high doses and during prolonged treatment) may slightly increase the risk of vascular thrombotic events (such as myocardial infarction or stroke). Insufficient data are available to exclude such risk with meloxicam use.

Therapy with meloxicam 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 initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk increases with duration of use. Patients with cardiovascular disease or cardiovascular risk factors have an increased risk of thrombotic complications.

Skin disorders

Life-threatening severe skin reactions—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 lesions), meloxicam treatment must be discontinued. Prompt diagnosis and discontinuation of any drug that may cause severe skin reactions—Stevens-Johnson syndrome or toxic epidermal necrolysis—are crucial, as early intervention improves prognosis. Meloxicam therapy must not be resumed at any time in the future if a patient has experienced Stevens-Johnson syndrome or toxic epidermal necrolysis during meloxicam use.

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

Anaphylactic reactions

As with other NSAIDs, anaphylactic reactions may occur in patients without prior exposure to meloxicam. The medicinal product 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 developed severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Immediate measures for anaphylactic reaction management should be taken if such a reaction occurs.

Liver parameters and renal function

Isolated cases of increased serum transaminases, serum bilirubin, or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory test abnormalities have been observed during NSAID treatment. In most cases, these abnormalities were mild and transient. Meloxicam should be discontinued and follow-up tests performed if significant or persistent abnormalities are confirmed.

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

Combination with pemetrexed

In patients with mild to moderate renal impairment receiving pemetrexed, meloxicam treatment should be 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 measures

Adverse reactions are often more severe in elderly, debilitated, or frail patients, who require careful monitoring. Caution is required when treating elderly patients, in whom reduced renal, hepatic, and cardiac function is more likely. Elderly patients have a higher incidence of adverse reactions with NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "Dosage and administration").

Like any NSAID, meloxicam may mask symptoms of infectious diseases.

With intramuscular administration of NSAIDs, abscess or necrosis may occur at the injection site.

Meloxicam use may adversely affect fertility and is therefore not recommended for women wishing to become pregnant. For women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam should be considered (see section "Use during pregnancy or lactation").

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

Masking of inflammation and fever

The pharmacological action of the medicinal product aimed at reducing fever and inflammation may diminish the diagnostic value of these signs in identifying complications of a suspected non-infectious painful condition.

Concomitant corticosteroid therapy

Meloxicam cannot 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, occult or macroscopic gastrointestinal bleeding, or effects on erythropoiesis. Hemoglobin or hematocrit levels should be monitored in patients receiving long-term NSAID therapy, including meloxicam, if symptoms or 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. Patients receiving meloxicam who are at risk of adverse effects on platelet function, such as bleeding disorders, and patients receiving anticoagulants, require careful monitoring.

Use in patients with asthma

Patients with 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 asthma.

Use during pregnancy or lactation.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and congenital heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increases 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 loss and embryofetal mortality. Furthermore, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, increased frequency of various developmental abnormalities, including cardiovascular, has been reported.

Starting from the 20th week of pregnancy, meloxicam use may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible upon discontinuation of therapy. Additionally, there have been reports of arterial duct constriction after treatment during the second trimester of pregnancy, which in most cases resolves after discontinuation of treatment. Meloxicam should not be used during the first and second trimesters of pregnancy except when strictly necessary. For women attempting to conceive and for pregnant women during the first and second trimesters, the dose and duration of meloxicam treatment should be as low as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction may be advisable after meloxicam exposure for several days starting from the 20th gestational week. Treatment should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
renal dysfunction (see above).

Potential risks in late pregnancy for mother and newborn:

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

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

Lactation. Although specific data on the medicinal product are lacking, NSAIDs are known to pass into breast milk. Therefore, use of the medicinal product is not recommended for women who are breastfeeding.

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

Ability to affect reaction speed when driving or operating machinery.

No specific studies on the effect of the medicinal product on the ability to drive a vehicle or operate machinery have been conducted. However, based on the pharmacodynamic profile and observed adverse reactions, meloxicam is likely to have no effect or a negligible effect on such activities. Nevertheless, patients experiencing visual disturbances, including blurred vision, dizziness, somnolence, vertigo, or other central nervous system disorders should 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 one injection at the beginning of therapy, with a maximum duration of up to 2–3 days in exceptional cases (when other routes of administration are not possible). Adverse reactions may 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 (see section "Pharmacokinetics"). The recommended dose for elderly patients is 7.5 mg daily (half of a 1.5 ml vial) (also see subsection "Patients at increased risk of adverse reactions" and section "Special Warnings and Precautions for Use").

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

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

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

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

Hepatic impairment. No dose reduction is required in patients with mild to moderate hepatic impairment. The medicinal product is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

Method of administration. For intramuscular use.

The 10 mg/ml injection solution should be administered by deep intramuscular injection into the upper outer quadrant of the buttock, strictly following aseptic technique. In case of repeated administration, it is recommended to alternate between left and right buttocks. Before injection, it is important to ensure that the needle tip has not entered 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 dosage forms (tablets) should be used.

Children.

ALOSCAM 10 mg/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 care. Gastrointestinal bleeding may occur. Severe poisoning may lead to arterial hypertension, acute renal failure, liver dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported during therapeutic use of NSAIDs and may also occur in overdose.

Treatment. Symptomatic and supportive measures are recommended for patients with NSAID overdose. Studies have shown accelerated elimination of meloxicam using oral doses of cholestyramine 4 g three times daily.

Adverse Reactions

Data from studies and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and during long-term treatment) may slightly increase the risk of vascular thrombotic events, such as myocardial infarction or stroke (see section "Special Warnings and Precautions for Use").

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

Most of the adverse reactions observed are gastrointestinal in origin. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported following NSAID use (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 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 count abnormalities (including changes in leukocyte count), leukopenia, thrombocytopenia.
Very rare cases of agranulocytosis have been reported (see "Specific serious and/or common adverse reactions" below).

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

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

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

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

Ear and labyrinth disorders:
uncommon – dizziness;
rare – tinnitus.

Cardiac disorders:
rare – palpitations. Heart failure associated with NSAID use has been reported.

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

Respiratory, thoracic and mediastinal disorders:
rare – asthma in patients with aspirin or other NSAID allergy;
frequency not known – upper respiratory tract infections, cough.

Gastrointestinal disorders:
very common – gastrointestinal disorders: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea;
uncommon – occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, eructation;
rare – colitis, gastroduodenal ulcer, esophagitis;
very rare – gastrointestinal perforation;
frequency not known – pancreatitis.
Gastrointestinal bleeding, ulcers, or perforation may be severe and potentially fatal, especially in elderly patients (see section "Special Warnings and Precautions for Use").

Hepatobiliary disorders:
uncommon – liver function test abnormalities (e.g., elevated transaminase or bilirubin levels);
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 (see section "Special Warnings and Precautions for Use").

Renal and urinary disorders:
uncommon – sodium and water retention, hyperkalemia (see sections "Special Warnings and Precautions for Use" and "Interaction with Other Medicinal Products and Other Forms of Interaction"), changes in renal function parameters (elevated serum creatinine and/or urea levels);
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, altered frequency of urination.

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, joint signs and symptoms.

Specific 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 typical of other compounds in the class:
Renal organic damage, which may lead to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported (see section "Special Warnings and Precautions for Use").

Reporting suspected adverse reactions. Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

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

Packaging. 1.5 ml in a vial, 5 vials in a blister pack, 1 blister pack in a carton.

Prescription status. Prescription only.

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

Address of manufacturer and location of its business activity.
36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.

Alsokam