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

Composition:

Active substance: meloxicam;

1 suppository contains meloxicam 15 mg;

Excipient: hard fat.

Pharmaceutical form. Rectal suppositories.

Main physicochemical characteristics: light yellow suppositories with a greenish tint, spherical in shape. A surface film on the suppository is permissible.

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

ATC code M01A C06.

Pharmacological Properties.

Pharmacodynamics.

Inflamin is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, exerting anti-inflammatory, analgesic, and antipyretic effects. Inflamin demonstrates high anti-inflammatory activity in all standard models of inflammation. The overall mechanism of these effects may be attributed to Inflamin's ability to inhibit the biosynthesis of prostaglandins—mediators of inflammation.

The safer mechanism of action of Inflamin is associated with its selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). The therapeutic effect of NSAIDs is linked to inhibition of COX-2 synthesis, whereas inhibition of COX-1 leads to adverse effects on the stomach and kidneys.

The selectivity of meloxicam in inhibiting COX-2 has been confirmed by numerous researchers both in vitro and ex vivo. Inflamin (15 mg) preferentially inhibits COX-2 ex vivo, as evidenced by greater inhibition of PGE2 production in response to lipopolysaccharide stimulation compared to thromboxane production in clotted blood (COX-1). These effects are dose-dependent. Inflamin does not affect platelet aggregation or bleeding time when recommended doses are used ex vivo, whereas indomethacin, diclofenac, ibuprofen, and naproxen significantly inhibit platelet aggregation and prolong bleeding.

Clinical studies have demonstrated a low incidence of gastrointestinal adverse events (perforations, ulceration, and bleeding) with the use of recommended doses of meloxicam compared to standard doses of other NSAIDs.

Pharmacokinetics.

Meloxicam is well absorbed from the gastrointestinal tract, reflected in its high absolute bioavailability (89%).

Bioequivalence between suppositories and capsules has been demonstrated. After administration of one suppository, maximum plasma concentration of meloxicam is reached within 5–6 hours.

Steady-state concentrations are achieved by day 3–5.

Single daily dosing results in plasma drug concentrations with relatively small fluctuations between peak and trough levels, ranging from 0.8–2 µg/mL for the 15 mg dose (Cmin and Cmax at steady-state equilibrium).

Maximum steady-state plasma concentration after administration of suppositories is reached after approximately 5 hours.

Continuous long-term treatment (e.g., 6 months) does not lead to changes in pharmacokinetic parameters compared to those observed after 2 weeks of treatment with 15 mg meloxicam daily. Any changes are also unlikely with treatment durations exceeding 6 months.

Distribution. In plasma, more than 99% is bound to plasma proteins (primarily albumin). Meloxicam penetrates into synovial fluid at concentrations approximately half of those in blood plasma.

The volume of distribution is low, averaging 11 liters. Individual variations range from 30–40%.

Biological Transformation. Meloxicam undergoes extensive biotransformation in the liver. It is almost completely metabolized into four pharmacologically inactive metabolites. 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 CYP2C9 plays a major role in metabolism, while CYP3A4 isoenzymes contribute to a lesser extent. Peroxidase activity in patients may be responsible for two other metabolites, accounting for 16% and 4% of the administered dose, respectively.

Excretion. Excretion of meloxicam occurs predominantly in the form of metabolites, in equal amounts via urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, while only trace amounts of unchanged drug are excreted in urine. Elimination half-life is approximately 20 hours.

Plasma clearance is 8 mL/min.

Special Patient Categories.

Hepatic and Renal Impairment. Hepatic or renal impairment does not significantly affect the pharmacokinetics of meloxicam. In end-stage renal disease, an increased volume of distribution may lead to elevated concentrations of free meloxicam.

Elderly Patients. Mean plasma clearance at steady-state equilibrium in elderly individuals was slightly lower than in younger individuals.

Clinical characteristics.

Indications.

Symptomatic treatment of:

Pain associated with osteoarthritis (arthrosis, degenerative joint diseases);
Rheumatoid arthritis;
Ankylosing spondylitis.

Contraindications.

Known hypersensitivity to meloxicam or to any other components of the drug.

Inflam must not be prescribed to patients who have symptoms of bronchial asthma, nasal polyps, angioneurotic edema, or urticaria associated with the use of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs), due to the possibility of cross-reactivity.

Additional contraindications include:

Active or recent history of gastrointestinal ulceration/perforation;
Pregnancy and breastfeeding period (see section "Use during pregnancy or lactation");
Pediatric age (under 18 years);
Gastrointestinal bleeding or perforation associated with previous NSAID therapy in medical history;
History of proctitis and rectal bleeding;
Active or recurrent peptic ulcer/gastrointestinal bleeding in history (two or more separate confirmed episodes of ulcer or bleeding);
Active inflammatory bowel disease (Crohn’s disease or ulcerative colitis);
Severe hepatic impairment;
Severe renal impairment without dialysis;
Gastrointestinal bleeding, cerebrovascular bleeding in history, or other coagulation disorders;
Other hemostasis disorders or concomitant therapy with anticoagulants;
Severe heart failure.

Do not use for the treatment of perioperative pain in coronary artery bypass grafting (CABG).

Interaction with other medicinal products and other forms of interaction.

Studies on interactions were conducted only in adults.

Risks associated with hyperkalemia. Certain medicinal products may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.

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

Pharmacodynamic interactions.

NSAIDs and acetylsalicylic acid. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), including acetylsalicylic acid at doses ≥500 mg per single dose or ≥3 g total daily dose.

Corticosteroids (e.g., glucocorticoids). Concomitant use with corticosteroids requires caution due to an 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 with anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses (see section "Special precautions for use").

In other cases (e.g., when administered at prophylactic doses), heparin use requires caution due to an increased risk of bleeding. Careful monitoring of INR (International Normalized Ratio) is necessary if such a combination cannot be avoided.

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

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

Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients), concomitant use of ACE inhibitors or angiotensin II antagonists with drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should receive adequate hydration, and renal function should be monitored after initiation of combination therapy and periodically thereafter (see section "Special precautions for use").

Other antihypertensive agents (e.g., β-blockers). Possible reduction in the 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 due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Close monitoring of renal function is recommended, especially in elderly patients.

Contraception. It has been reported that NSAIDs may reduce the effectiveness of intrauterine devices, but these data require further confirmation.

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 indicate that NSAIDs increase plasma lithium concentrations (due to reduced renal excretion of lithium), potentially reaching 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. For this reason, 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, particularly those with impaired renal function. If combination therapy is required, blood parameters and renal function should be monitored. Caution is advised when NSAID and methotrexate administration occurs for three consecutive days, as plasma methotrexate levels may increase and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, hematological toxicity of methotrexate may increase with NSAID therapy (see above and section "Adverse reactions").

Pemetrexed. When concomitant use of meloxicam with pemetrexed is required in patients with mild to moderate renal impairment (creatinine clearance from 45 to 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 is advised when administering 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. Cholestyramine accelerates the elimination of meloxicam due to disruption of enterohepatic circulation, resulting in a 50% increase in meloxicam clearance and a reduction in half-life to 13±3 hours. This interaction is clinically significant.

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

Oral antidiabetic agents (sulfonylureas, nateglinide). Meloxicam is almost entirely eliminated via hepatic metabolism, approximately two-thirds mediated by cytochrome P450 (CYP) enzymes (mainly CYP 2C9 and secondarily CYP 3A4) and one-third via other pathways, such as peroxidase oxidation. Potential pharmacokinetic interactions should be considered when meloxicam is administered concomitantly with medicinal products that strongly inhibit or are metabolized by CYP 2C9 and/or CYP 3A4. Interactions mediated by CYP 2C9 may be expected when combining meloxicam with medicinal products such as oral antidiabetic agents (sulfonylureas, nateglinide); such interactions may lead to increased plasma levels of both agents. Patients receiving meloxicam and sulfonylurea or nateglinide should be closely monitored for the development of hypoglycemia.

No clinically significant pharmacokinetic interactions were 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, and 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 is not suitable for the treatment of patients requiring relief from 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 healing before initiating meloxicam therapy. The possibility of recurrence should be considered in patients treated with meloxicam and in those with such history.

Gastrointestinal disorders.

As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without prior symptoms or serious gastrointestinal conditions in history.

The risk of gastrointestinal bleeding, ulceration, or perforation is higher with increasing NSAID doses in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should initiate treatment with the lowest effective dose. For such patients, as well as for patients requiring concomitant use of low-dose aspirin or other drugs increasing gastrointestinal risks, combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered (see 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 taking medicinal products that increase the risk of ulceration or bleeding, including heparin as radical therapy or in geriatric practice, anticoagulants such as warfarin, or other NSAIDs, including acetylsalicylic acid at doses ≥500 mg per dose or ≥3 g total daily dose (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment with this drug 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.

Up to 15% of patients receiving NSAIDs (including meloxicam) may have elevated values of one or more liver function tests. Such laboratory abnormalities may progress, remain unchanged, or resolve during continued treatment. Marked elevations in ALT [alanine aminotransferase] or AST [aspartate aminotransferase] (approximately 3 times or more above normal) were observed in 1% of patients during clinical trials with NSAIDs. Rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis, and liver failure, sometimes fatal, have also been reported.

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

Cardiovascular disorders. Patients with arterial hypertension and/or a history of mild to moderate congestive heart failure require careful monitoring, as fluid retention and edema have been observed during NSAID therapy.

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

Data from studies and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and during prolonged treatment) may slightly increase the risk of vascular thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to exclude such risk with meloxicam use.

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

NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. This risk increases with prolonged use of the drug and in patients with cardiovascular diseases or cardiovascular risk factors.

Skin disorders. Life-threatening severe skin reactions, such as 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, toxic epidermal necrolysis. This is associated with a better prognosis in severe skin reactions. If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis during meloxicam therapy, the drug must never be restarted in the future.

Cases of fixed drug eruption have been reported with meloxicam use.

Meloxicam should not be re-prescribed 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 who have not previously reacted 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 developed severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency measures should be taken if an anaphylactoid reaction is detected.

Liver function and kidney function parameters. As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, elevated serum bilirubin, or other liver function parameters, increased serum creatinine, blood urea nitrogen, and other laboratory parameter abnormalities have been described. These abnormalities were mostly minor and transient. If significant or persistent abnormalities are confirmed, meloxicam use should be discontinued and follow-up tests performed.

Functional renal impairment. By inhibiting the vasodilatory effect of renal prostaglandins, NSAIDs may induce functional renal failure due to decreased glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of diuresis and renal function is recommended at the beginning of treatment or after dose increase in patients with the following risk factors:

advanced age;
concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other forms of interaction");
hypovolemia (of any origin);
congestive heart failure;
renal failure;
nephrotic syndrome;
lupus nephropathy;
severe hepatic dysfunction (serum albumin <25 g/L or Child-Pugh score ≥10).

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

The dose of meloxicam in patients with end-stage renal failure on dialysis should not exceed 7.5 mg (as tablets). For patients with mild or moderate renal impairment, the dose need not be reduced (creatinine clearance level exceeds 25 mL/min).

Sodium, potassium, and water retention. NSAIDs may enhance sodium, potassium, and water retention and affect the natriuretic effects of diuretics. Additionally, a reduction in the antihypertensive effect of antihypertensive drugs may occur (see section "Interaction with other medicinal products and other forms of interaction"). As a result, edema, heart failure, or arterial hypertension may be accelerated or exacerbated in susceptible patients. Therefore, clinical monitoring is recommended for patients with such risks (see sections "Dosage and administration" and "Contraindications").

Hyperkalemia. Hyperkalemia may be promoted 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. When concomitant use of meloxicam with pemetrexed is required in patients with mild to moderate renal impairment, meloxicam treatment should be withheld at least 5 days before pemetrexed administration, on the day of administration, and for at least 2 days after administration (see section "Interaction with other medicinal products and other forms of interaction").

Other warnings and safety measures.

Adverse reactions are often poorly tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with treatment with other NSAIDs, caution is required in elderly patients, in whom reduced kidney, liver, and heart function is more likely. In elderly patients, the frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal, is higher (see section "Dosage and administration").

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

The use of meloxicam may negatively 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 (see section "Use during pregnancy or breastfeeding").

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

Concomitant corticosteroid therapy. Meloxicam cannot replace corticosteroids in corticosteroid deficiency.

Hematological effects. Anemia may occur in patients receiving NSAIDs, including meloxicam. This may be related to fluid retention, gastrointestinal bleeding (either occult or macroscopic), or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit levels should be monitored during long-term treatment with NSAIDs, including meloxicam, if symptoms and signs of anemia are present.

NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, short-term, and reversible. Patients taking meloxicam who may have adverse effects on platelet function, particularly coagulation disorders, and those receiving anticoagulants should be carefully monitored.

Use in patients with asthma. Patients with asthma may have aspirin-induced asthma. Use of aspirin in patients with aspirin-induced asthma is associated with severe bronchospasm, which may be fatal. Due to cross-reactivity, including bronchospasm, between aspirin and other NSAIDs, meloxicam should not be used in patients sensitive to aspirin and should be used cautiously in patients with asthma.

Use during pregnancy or breastfeeding.

Pregnancy. Meloxicam is contraindicated during pregnancy.

Use of meloxicam from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic and fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects, and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. This risk is believed to increase with increasing dose and duration of treatment.

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

cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
renal impairment, which may progress to renal failure with oligohydramnios.

Potential risks in late pregnancy for the mother and newborn:

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

Although specific data on meloxicam are lacking, NSAIDs are known to cross into breast milk; therefore, meloxicam is contraindicated in women who are breastfeeding.

Fertility. Meloxicam, like other medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, may negatively 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 drug on the ability to drive a car or operate machinery have been conducted. Based on the pharmacodynamic profile and observed adverse reactions, meloxicam is expected to have no effect or a negligible effect on such activities. However, patients experiencing visual disturbances, including blurred vision, dizziness, somnolence, vertigo, or other central nervous system disorders, are advised to refrain from driving and operating machinery.

Administration and Dosage

Before using the suppository, it is necessary to:

Tear off one suppository along the perforation line of the blister pack in the primary packaging;
Then pull the edges of the film apart in opposite directions to remove the suppository from its primary packaging.

For adults:

Osteoarthritis: 15 mg/day (1 suppository).

Rheumatoid arthritis: 15 mg/day (1 suppository).

Ankylosing spondylitis: 15 mg/day (1 suppository).

The maximum recommended daily dose of meloxicam for adults is 15 mg.

Since the risk of adverse reactions increases with higher doses and longer duration of treatment, the lowest effective daily dose should be used for the shortest possible treatment period.

When combining different dosage forms of meloxicam (capsules, tablets, suppositories, solution), the total daily dose must not exceed 15 mg.

Children. The drug is not intended for use in children under 18 years of age.

Overdose.

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 cases of overdose.

In cases of NSAID overdose, symptomatic and supportive treatment is recommended for patients. According to study results, oral administration of cholestyramine at 4 g three times daily accelerates the elimination of meloxicam.

Adverse Reactions

Most adverse effects of the medicinal product are gastrointestinal in origin. Peptic ulcer, perforation, or gastrointestinal hemorrhage, sometimes fatal, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). After administration of meloxicam, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn's disease have been observed (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.

Data from clinical trials and epidemiological studies suggest that the use of certain NSAIDs (especially at high doses and during long-term treatment) may be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special Warnings and Precautions for Use").

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

Serious skin reactions have also been reported with NSAID use, including 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 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); 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 – agranulocytosis (see "Specific serious and/or common adverse reactions" below).

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

Psychiatric disorders: rare – mood changes, nightmares; 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 therapy has also 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; 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. Gastrointestinal bleeding, ulceration, or perforation may be severe and may result in fatal outcomes, particularly in elderly patients (see section "Special Warnings and Precautions for Use"); not known – pancreatitis.

Hepatobiliary disorders: uncommon – liver function abnormalities (e.g., increased transaminase or bilirubin levels); very rare – hepatitis; 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; 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); very rare – acute renal failure, particularly in patients with risk factors (see section "Special Warnings and Precautions for Use"); not known – urinary tract infections, disturbances in micturition frequency.

General disorders and administration site conditions: uncommon – edema, including edema of the lower limbs; not known – influenza-like symptoms.

Musculoskeletal and connective tissue disorders: 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 treated with meloxicam and other potentially myelotoxic medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

Adverse reactions not observed during use of the product but typical for 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").

Reporting of suspected adverse reactions. Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 5 suppositories per blister; 2 blisters per carton.

Prescription status. Prescription only.

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

Manufacturer's address.
36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.