Algezicam®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALGEZIKAM® (Algezikam®)

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. Injection solution.

Main physicochemical properties: clear, yellow solution 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 has demonstrated high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its exact mechanism of action remains unknown. However, there is a common mechanism of action shared by all NSAIDs (including meloxicam): inhibition of prostaglandin biosynthesis, which are mediators of inflammation.

Pharmacokinetics.

Absorption. Meloxicam is completely absorbed after intramuscular injection. The relative bioavailability compared to oral administration is nearly 100%. Therefore, dose adjustment is not required when switching from intramuscular to oral administration. After intramuscular injection of 15 mg, the maximum plasma concentration (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 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 ranging from 7% to 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. Elimination of meloxicam occurs primarily as metabolites in equal proportions in urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, and a negligible amount is excreted in urine. The elimination half-life ranges from 13 to 25 hours, depending on the route of administration (oral, intramuscular, or intravenous). Plasma clearance is approximately 7–12 mL/min after a single oral, intravenous, or rectal dose.

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 does 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 higher concentrations of free meloxicam. The daily dose should not exceed 7.5 mg (see section "Dosage and administration").

Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, the area under the plasma concentration-time curve (AUC) is higher and the elimination half-life is longer compared to young volunteers of either sex. Mean plasma clearance at steady state in elderly patients was slightly lower than in young volunteers.

Clinical characteristics.

Indications.

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

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 other component 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 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 history (two or more separate confirmed episodes of ulcer or bleeding);
• severe hepatic impairment;
• severe renal impairment without dialysis;
• gastrointestinal bleeding, cerebrovascular bleeding in history, or other bleeding disorders;
• coagulation 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.

Studies on interactions were conducted only in adults.

Risks associated with hyperkalemia. Some medicinal products or therapeutic groups may cause hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme 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 developing hyperkalemia increases with concomitant use of the above-mentioned medicinal products and 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"), as well as with 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 bleeding or risk of gastrointestinal ulceration.

Anticoagulants or heparin. The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use"). Concomitant use of NSAIDs and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses (see section "Special precautions for use"). 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 using prophylactic doses), caution is required when administering heparin due to increased risk of bleeding.

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

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

Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors or angiotensin II antagonists and cyclooxygenase-inhibiting medicinal products may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. 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 agents (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. Data exist for NSAIDs increasing plasma lithium concentrations (by reducing renal excretion of lithium), which may reach toxic levels. Concomitant use of lithium and NSAIDs is not recommended (see section "Special precautions for use"). If combination therapy is necessary, plasma lithium levels should be closely monitored at the start of treatment, during dose adjustment, and upon discontinuation of meloxicam.

Methotrexate. NSAIDs may reduce tubular secretion of methotrexate, thereby increasing its plasma concentration. Therefore, concomitant use of NSAIDs is not recommended in patients receiving high-dose methotrexate (over 15 mg/week) (see section "Special precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low-dose methotrexate, including those with impaired renal function. If combination therapy is required, blood test parameters and renal function must be monitored. Caution is advised when NSAID and methotrexate administration continues for 3 consecutive days, as plasma methotrexate levels may increase and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, hematological toxicity of methotrexate may increase during NSAID treatment (see above) (see section "Adverse reactions").

Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45–79 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 < 45 mL/min).

In patients with normal renal function (creatinine clearance ≥ 80 mL/min), a 15 mg dose of meloxicam may reduce pemetrexed elimination and thus increase the frequency of pemetrexed-related adverse reactions. Therefore, caution should be exercised when prescribing 15 mg meloxicam 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 the elimination of meloxicam by disrupting enterohepatic circulation, thus increasing meloxicam clearance by 50% and reducing its elimination 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 (sulfonylureas, nateglinide). Meloxicam is almost entirely metabolized in the liver, approximately two-thirds mediated by cytochrome P450 (CYP) enzymes (mainly CYP 2C9 and minor CYP 3A4) and one-third by 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 antidiabetics (sulfonylureas, 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 the development of hypoglycemia.

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

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

The medicinal product ALGEXICAM® 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 clinical benefits of continued therapy 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. The possibility of recurrence should be considered 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, with or without warning symptoms or a history of serious gastrointestinal disorders.

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. 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 medicinal products that increase gastrointestinal risks (see information below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, especially elderly patients, should be informed about any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

Concomitant use of meloxicam is not recommended in patients receiving medicinal products that may increase the risk of ulceration or bleeding, such as heparin as radical therapy or in geriatric practice, anticoagulants such as warfarin or other NSAIDs, or acetylsalicylic acid at doses ≥ 500 mg per dose, or ≥ 3 g total daily dose (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment should be discontinued.

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

Hepatic disorders

Elevations in one or more liver function tests may occur in approximately 15% of patients receiving NSAIDs (including meloxicam). These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations in ALT or AST (approximately 3 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 those in whom liver function test abnormalities have occurred should be monitored for the development of signs of more severe hepatic failure during meloxicam therapy. If clinical signs and symptoms suggest hepatic disease or if systemic manifestations of disease (e.g., eosinophilia, rash) occur, use of the medicinal product ALGEXICAM® should be discontinued.

Cardiovascular disorders

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

Clinical monitoring of blood pressure is recommended at the beginning of therapy, especially at the start of meloxicam treatment, in patients with risk factors.

Data from studies and epidemiological data suggest that 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 (myocardial infarction or stroke). There are insufficient data to exclude such risk for meloxicam.

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

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

Skin disorders

Life-threatening severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam use. Patients should be informed about signs and symptoms of severe skin reactions and closely monitored for skin reactions. The highest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis occurs during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., progressive skin rash often with blisters or mucosal involvement), meloxicam treatment must be discontinued. Rapid diagnosis and discontinuation of any drug that may cause severe skin reactions—Stevens-Johnson syndrome or toxic epidermal necrolysis—is essential, as this is associated with a better prognosis in severe skin reactions. If a patient has experienced Stevens-Johnson syndrome or toxic epidermal necrolysis with meloxicam, the drug must not be used in the future. 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 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 medicinal product ALGEXICAM® should not be used in patients with aspirin triad. This symptomatic complex occurs in patients with asthma who have a history of rhinitis with or without nasal polyps, or who experience severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Immediate emergency measures should be taken if an anaphylactic reaction occurs.

Liver parameters and renal function

As 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 test abnormalities have been reported with meloxicam use. In most cases, these abnormalities were mild and transient. If significant or persistent abnormalities are confirmed, meloxicam use 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 diuresis and renal function is recommended at the beginning of treatment or after dose escalation 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 on 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. Dose adjustment is not required in patients with mild to moderate renal impairment (creatinine clearance > 25 mL/min).

Sodium, potassium and water retention

NSAIDs may enhance retention of sodium, potassium and water and may interfere with 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 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 caused by diabetes 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 less well tolerated in elderly, debilitated or frail patients, who require careful monitoring. As with treatment with other NSAIDs, caution is required in elderly patients, in whom reduced renal, hepatic and cardiac function is more likely. Elderly patients have a higher incidence of adverse reactions to 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.

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

Meloxicam may negatively affect female fertility; therefore, this medicinal product is 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 breastfeeding").

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

Masking of inflammation and fever

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

Glucocorticoid therapy

The medicinal product ALGEXICAM® cannot be considered a substitute for glucocorticoids in the treatment of glucocorticoid insufficiency.

Hematological effects

Anemia may occur in patients receiving NSAIDs, including ALGEXICAM®. 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 receiving long-term treatment with ALGEXICAM® 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 less, short-term and reversible. Patients receiving ALGEXICAM® who are at risk of adverse reactions 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, the medicinal product ALGEXICAM® should not be used in patients hypersensitive to acetylsalicylic acid and should be used with caution in patients with asthma.

Use during pregnancy or breastfeeding.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and congenital heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. This risk is considered to increase with increasing dose and duration of treatment.

From the 20th week of gestation, use of meloxicam may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. In addition, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after discontinuation. Meloxicam should not be used during the first and second trimesters of pregnancy, except when strictly necessary. 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. Monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to meloxicam for several days starting from the 20th gestational week. Use of ALGEXICAM® should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

• cardiopulmonary toxicity (with premature constriction/closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligohydramnios (see above).

Potential risks in late pregnancy for mother and newborn:

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

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

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

Fertility. ALGEXICAM®, like other medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, may negatively affect female 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.

Ability to influence 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. However, based on the pharmacodynamic profile and observed adverse reactions, meloxicam has no effect or a negligible effect on these activities. Nevertheless, patients experiencing visual disturbances, including blurred vision, dizziness, somnolence, vertigo or other central nervous system disorders, are advised to refrain from driving or operating machinery.

Method of Administration and Dosage

Dosing

Administered intramuscularly.

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").

The patient's need for symptomatic 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 ampoule) (also see section "Method of Administration and Dosage" ("Patients at Increased Risk of Adverse Reactions") and section "Special Warnings and Precautions for Use").

Patients at Increased Risk of Adverse Reactions (see section "Special Warnings and Precautions for Use")

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

Renal Impairment

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

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

Hepatic Impairment

Dose reduction 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 preparation should be administered slowly by deep intramuscular injection into the upper outer quadrant of the buttock under aseptic conditions. When repeated administration is necessary, alternate injections between the left and right buttocks. Prior to injection, it is important to ensure that the needle tip has not entered a blood vessel.

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

In the case of a hip prosthesis, the injection should be administered into the opposite buttock.

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

Children

ALGEXICAM® 15 mg/1.5 mL injection solution is contraindicated in children (under 18 years of age) (see section "Contraindications").

Overdose

Symptoms

Symptoms of acute overdose with ALGEXICAM® are generally limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are usually reversible with supportive treatment. Gastrointestinal bleeding may occur. Severe poisoning may lead to arterial hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, seizures, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported during therapeutic use of NSAIDs and may also occur in overdose.

Treatment

In case of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown accelerated elimination of meloxicam with four oral doses of cholestyramine administered three times daily.

Adverse Reactions

Data from studies and epidemiological evidence suggest that the use of certain NSAIDs (especially at high doses and during long-term treatment) may be associated with a small increased risk of vascular thrombotic events, such as myocardial infarction or stroke (see section "Special precautions").

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

Most adverse reactions observed with the use of the medicinal product ALGIZIKAM® are of gastrointestinal origin. Peptic ulcer, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn's disease have been reported following administration (see section "Special precautions"). Gastritis has been observed less frequently.

Severe skin reactions have been reported: Stevens-Johnson syndrome and toxic epidermal necrolysis (see section "Special precautions").

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the 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 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 – 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 precautions"), 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 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 can be severe and potentially fatal, particularly in elderly patients (see section "Special precautions").

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

Skin and subcutaneous tissue disorders:
uncommon – 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 (see section "Special precautions").

Renal and urinary disorders:
uncommon – sodium and water retention, hyperkalemia (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions"), 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 precautions");
frequency not known – urinary tract infections, changes 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 lower limb 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 taking meloxicam and other potentially myelotoxic medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

Adverse reactions not associated with the use of the drug but generally recognized as typical for other compounds of the class. Organic kidney damage, which may lead to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, and papillary necrosis have been reported (see section "Special precautions").

Reporting suspected adverse reactions. Reporting suspected adverse reactions after medicinal product authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy through 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 reach of children.

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

Prescription category. Prescription only.

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

Manufacturer's address and location of its business activities.
36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.