Revmalgine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT REVMALGIN (REUMALGIN)

Composition:

Active substance: meloxicam;

1 suppository contains meloxicam equivalent to 100% dry substance 15 mg;

Excipients: hard fat, polyoxyl hydrogenated castor oil.

Pharmaceutical form. Rectal suppositories.

Main physicochemical properties: smooth, yellowish-green colored suppositories. On longitudinal section, absence of inclusions; presence of funnel-shaped depression and air channel is acceptable.

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, exerting anti-inflammatory, analgesic, and antipyretic effects. Meloxicam demonstrates high anti-inflammatory activity in all standard models of inflammation. The overall mechanism of these effects may be attributed to meloxicam's ability to inhibit the biosynthesis of prostaglandins—mediators of inflammation.

The improved safety profile of meloxicam 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 for COX-2 inhibition has been confirmed by numerous researchers both in vitro and ex vivo. Meloxicam (15 mg) preferentially inhibits COX-2 ex vivo, as evidenced by substantial inhibition of PGE2 production in response to lipopolysaccharide stimulation, compared to thromboxane production in clotting blood (COX-1). These effects are dose-dependent. Meloxicam does not affect platelet aggregation or bleeding time when administered at recommended doses 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 recommended doses of meloxicam compared to standard doses of other NSAIDs.

Pharmacokinetics.

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

After administration of a single dose of suppositories, maximum plasma concentration of meloxicam is reached within 5–6 hours.

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

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

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

Continuous treatment over a prolonged period (e.g., 6 months) did not result in 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 duration exceeding 6 months.

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

Volume of distribution is low, averaging 11 L. 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 the administered dose), is formed via oxidation of the intermediate metabolite 5’-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of the dose). In vitro studies suggest that CYP2C9 plays a major role in metabolism, while CYP3A4 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. Excretion of meloxicam occurs predominantly in the form of metabolites, equally in urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, while only traces of unchanged drug are excreted in urine. Elimination half-life is approximately 20 hours.

Plasma clearance is 8 mL/min.

Special patient populations.

Hepatic and renal impairment.

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

Elderly patients.

Mean plasma clearance at steady-state equilibrium in elderly patients 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.

• Hypersensitivity to meloxicam or any of the excipients of the medicinal product, or to active substances with similar actions, such as NSAIDs, aspirin. Meloxicam should not be administered to patients who have experienced asthma, nasal polyps, angioedema, or urticaria after taking aspirin or other NSAIDs;
• Pregnancy and breastfeeding period (see section "Use during pregnancy or breastfeeding");
• Pediatric age (under 18 years);
• Gastrointestinal bleeding or perforation related to previous NSAID therapy, in medical history;
• History of proctitis and rectal bleeding;
• Active or recurrent peptic ulcer/hemorrhage in medical history (two or more separate confirmed episodes of ulcer or bleeding);
• Active inflammatory bowel disease (Crohn’s disease or ulcerative colitis);
• Severe hepatic insufficiency;
• Severe renal insufficiency without dialysis;
• Gastrointestinal bleeding, cerebrovascular hemorrhage in medical history, or other coagulation disorders;
• Other hemostasis disorders or concomitant therapy with anticoagulants;
• Severe heart failure;
• Treatment of perioperative pain in coronary artery bypass grafting.

Interaction with other medicinal products and other types of interactions.

Interaction studies were conducted only in adults.

Risks associated with hyperkalemia.

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

The onset of hyperkalemia may depend on associated factors. 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. Combination with other NSAIDs is not recommended (see section "Special precautions for use"), including 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 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 and 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 used at prophylactic doses), heparin administration requires caution due to an increased risk of bleeding. Careful monitoring of INR (International Normalized Ratio) is necessary if such combination cannot be avoided.

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

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

Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors or angiotensin II antagonists and cyclooxygenase-inhibiting agents 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. Adequate hydration should be ensured, and renal function should be monitored after initiation of combined therapy and periodically thereafter (see section "Special precautions for use").

Other antihypertensive medicinal products (e.g., beta-blockers). As with the medicinal products mentioned 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 due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Careful 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 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 (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 are taken for 3 consecutive days, as plasma methotrexate levels may rise and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, hematological toxicity of methotrexate may increase during NSAID therapy (see information provided above) (see section "Adverse reactions").

Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance of 45–79 mL/min), meloxicam administration should be withheld 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 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 (primarily 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 combined with medicinal products such as oral antidiabetics (sulfonylureas, nateglinide); such interactions may lead to increased plasma levels of these agents and meloxicam. Patients receiving meloxicam and sulfonylurea or nateglinide should be closely monitored for the development of hypoglycemia.

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 treatment of patients requiring relief of acute pain.

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

Particular attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer to ensure complete healing prior to initiating meloxicam therapy. Recurrence should always 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 therapy, with or without prior symptoms or serious gastrointestinal disease 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. Such patients should be started on 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 aspirin or other medicinal products increasing gastrointestinal risks (see information below and section "Interaction with other medicinal products and other forms of interaction").

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

Meloxicam is not recommended for patients who are concurrently using medicinal products that may increase the risk of ulceration or bleeding, such as heparin used as definitive therapy or in geriatric practice, anticoagulants such as warfarin, or other nonsteroidal anti-inflammatory drugs, 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 gastrointestinal disorders in their history (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 levels of one or more liver function tests. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations of ALT or AST (approximately three times or more above normal) were observed in 1% of patients during clinical trials with NSAIDs. Additionally, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported.

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

Cardiovascular disorders.

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

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

Clinical and epidemiological data suggest that use of certain NSAIDs (especially at high doses and during prolonged treatment) may be associated with a small increased risk of vascular thrombotic events (e.g., myocardial infarction or stroke). There are insufficient data to exclude such risk for meloxicam.

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

NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. This risk increases with prolonged use and in patients with cardiovascular disease 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 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. Prompt diagnosis and discontinuation of any drug that may cause severe skin reactions—Stevens-Johnson syndrome, toxic epidermal necrolysis—are crucial, as early intervention improves prognosis for severe skin reactions. Meloxicam must never be restarted in patients who developed Stevens-Johnson syndrome or toxic epidermal necrolysis during meloxicam therapy.

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.

Potential cross-reactivity may occur with other oxicams.

Anaphylactic reactions.

As with other NSAIDs, anaphylactic reactions may occur in patients without known prior sensitivity to meloxicam. Meloxicam 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 experienced severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency measures should be taken if an anaphylactoid reaction occurs.

Liver function tests and renal function.

As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, elevated serum bilirubin, or other liver function test abnormalities, increased serum creatinine, blood urea nitrogen, and other laboratory test abnormalities have been reported. 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, by inhibiting the vasodilatory effect of renal prostaglandins, may induce functional renal impairment due to decreased glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of diuresis and renal function is recommended at the beginning of treatment or after dose increase in patients with the following risk factors:

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

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

The dose of meloxicam in patients with end-stage renal disease on dialysis should not exceed 7.5 mg (as tablets). For patients with mild or moderate renal impairment, dose reduction is not required (creatinine clearance > 25 mL/min).

Sodium, potassium, and water retention.

NSAIDs may enhance sodium, potassium, and water retention and affect the natriuretic effects of diuretics. 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 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"). Regular monitoring of potassium levels is required in such cases.

Combination with pemetrexed.

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

Other warnings and safety precautions.

Adverse reactions are often less well tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with other NSAIDs, caution is required in elderly patients, in whom reduced renal, hepatic, and cardiac function is more likely. The frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal, is higher in elderly patients (see section "Dosage and administration").

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

Meloxicam use may negatively affect fertility 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.

REVMALGIN cannot substitute for corticosteroids in the treatment of corticosteroid insufficiency.

Hematological effects.

Anemia may occur in patients receiving NSAIDs, including meloxicam. This may be related to fluid retention, gastrointestinal bleeding (either occult or macroscopic), or incompletely described effects on erythropoiesis. Patients undergoing long-term treatment with NSAIDs, including meloxicam, should have hemoglobin or hematocrit monitored if symptoms or 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 smaller, short-term, and reversible. Close monitoring is required for patients taking meloxicam who may experience adverse effects related to platelet function, such as coagulation disorders, or for patients receiving anticoagulants.

Use in patients with asthma.

Patients with asthma may have aspirin-sensitive asthma. Aspirin use in patients with aspirin-sensitive 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 hypersensitive to aspirin and should be used cautiously in patients with asthma.

Use during pregnancy or breastfeeding.

Fertility. Meloxicam, like other medicinal products inhibiting 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.

Pregnancy. Meloxicam is contraindicated during pregnancy.

Use of meloxicam from the 20th week of gestation may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation of the drug. Additionally, cases of fetal ductus arteriosus constriction have been reported after second-trimester treatment, most of which resolved after treatment cessation. Therefore, meloxicam should not be prescribed during the first and second trimesters unless clearly needed. If meloxicam is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered if meloxicam exposure occurs for several days starting from the 20th gestational week. Meloxicam use should be discontinued if oligohydramnios or ductus arteriosus constriction is detected in the fetus.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic and fetal development. Epidemiological data suggest an increased risk of miscarriage, cardiac 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 dysfunction, 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 pass into breast milk; therefore, meloxicam is contraindicated in breastfeeding women.

Ability to influence reaction speed when driving or operating machinery.

No specific studies on the effect of the drug on the ability to drive a vehicle or operate machinery have been conducted. However, based on the pharmacodynamic profile and observed adverse reactions, meloxicam is likely to have no or negligible effect on such activities. Nevertheless, 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.

Method of Administration and Dosage.

Osteoarthritis: 15 mg/day (1 suppository).

Rheumatoid arthritis: 15 mg/day (1 sup游戏副本).

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

The maximum recommended daily dose of meloxicam 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 duration necessary.

When combining different dosage forms of the drug (capsules, tablets, suppositories, suspension, or injection solution), the total daily dose of meloxicam 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 treatment. Gastrointestinal bleeding may occur. Severe poisoning may lead to arterial hypertension, acute renal failure, liver 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 cases of overdose.

In cases of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown that the elimination of meloxicam can be accelerated by oral administration 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 be associated with a small increased risk of vascular thrombotic events (e.g., 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 effects 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"). Following administration, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.

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

Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); 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 cases of agranulocytosis have been reported (see section "Specific Serious and/or Common Adverse Reactions").

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 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 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.

Gastrointestinal bleeding, ulceration, or perforation may be severe and potentially fatal, especially in elderly patients (see section "Special Warnings and Precautions for Use");
Not known – pancreatitis.

Hepatobiliary disorders:

Uncommon – abnormal liver function tests (e.g., elevated transaminases or bilirubin);
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, changes in micturition frequency.

General disorders and administration site conditions:

Uncommon – edema, including peripheral edema;
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 the use of the medicinal product but generally recognized as characteristic of other compounds in the class.

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

Shelf life. 3 years.

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

Packaging.

5 suppositories per strip. 1 or 2 strips per carton.

Prescription status. Prescription only.

Manufacturer. LLC "FARMEKS GROUP".

Manufacturer's address and place of business.

100, Shevchenka Street, Boryspil, Kyiv Oblast, Ukraine, 08301.