Algezicam®

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

Composition:

Active ingredient:
meloxicam;

1 tablet contains 15 mg of meloxicam;

Excipients:
microcrystalline cellulose (type 102), lactose monohydrate, sodium citrate, crospovidone, povidone K30, magnesium stearate, colloidal anhydrous silicon dioxide.

Pharmaceutical form.
Tablets.

Main physicochemical properties:
round, flat uncoated tablets with a uniform outer layer, compact and homogeneous structure, intact edges, yellowish in color, 9 mm in diameter, with a break line on one side.

Pharmacotherapeutic group.
Non-steroidal anti-inflammatory drugs (NSAIDs) and antirheumatic agents.

ATC code M01AC06.

Pharmacological properties.

Pharmacodynamics.

Algezicam® is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties.

Meloxicam has demonstrated high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its precise 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.

The oral bioavailability of meloxicam is on average 89%. After a single dose of meloxicam in solid oral dosage form (tablets), maximum plasma concentration is reached within 5–6 hours.

When meloxicam is administered, plasma concentration of the drug is proportional to the dose (Cmin and Cmax at steady state): 0.8–2.0 mg/L. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%).

Meloxicam is mainly metabolized via oxidation of the methyl group attached to the thiazolyl ring. The main metabolite, 5'-carboxymeloxicam (60% of dose), is formed through oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted in small amounts (9% of dose).

Only 3% of the dose is excreted unchanged; half is excreted via urine and half via feces.

The mean elimination half-life is approximately 20 hours.

In vitro studies have shown that the CYP 2C9 isoenzyme plays a significant role in meloxicam metabolism, while processes involving CYP 3A4 are of lesser importance.

Steady-state levels are achieved within 5 days.

The average plasma clearance is approximately 8 mL/min. The volume of distribution is low, averaging 11 L. Individual variability is about 30–40%.

In end-stage renal failure, an increased volume of distribution may lead to higher free meloxicam concentrations; therefore, the daily dose of 7.5 mg (half of a 15 mg tablet) of meloxicam should not be exceeded.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of osteoarthritis exacerbation.

Long-term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis.

Contraindications.

• Hypersensitivity to meloxicam or to any other component of the medicinal product, or to active substances with similar action, such as NSAIDs, aspirin. Meloxicam should not be administered to patients who have experienced asthma symptoms, nasal polyps, angioedema, or urticaria after taking aspirin or other NSAIDs;
• Active peptic ulcer or history of peptic ulcer;
• Gastrointestinal bleeding or perforation, including those associated with previous NSAID therapy, cerebrovascular bleeding, or other hemorrhagic disorders;
• Severe hepatic insufficiency;
• Severe renal insufficiency not amenable to dialysis;
• Pediatric age under 16 years;
• Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
• Severe heart failure;
• Treatment of perioperative pain in coronary artery bypass grafting.

Interaction with other medicinal products and other forms of interaction.

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.

Other nonsteroidal anti-inflammatory drugs (NSAIDs), including high-dose 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 increased risk of gastrointestinal bleeding or ulceration.

Oral anticoagulants, ticlopidine, heparin, and thrombolytic agents.
The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may potentiate 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, heparin use requires caution due to increased bleeding risk. Careful monitoring of INR (International Normalized Ratio) is necessary if this combination cannot be avoided.

Lithium.
NSAIDs may increase plasma lithium concentrations (due to reduced 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, particularly those with impaired renal function. If combination therapy is necessary, blood parameters and renal function should be monitored. Caution is advised if NSAID and methotrexate are taken for three 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 above) (see section "Adverse reactions").

Pemetrexed.
When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance from 45 to 79 mL/min), meloxicam should be withheld for 5 days before, on the day of, and 2 days after pemetrexed administration. If combination of meloxicam with pemetrexed is necessary, patients must be closely monitored. 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 dose of 15 mg 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).

Diuretics.
In dehydrated patients, NSAID therapy is associated with a potential risk of acute renal failure. Adequate hydration and careful monitoring of renal function should be ensured after initiation of concomitant therapy.

Antihypertensive medicinal products (e.g., beta-blockers).
When NSAIDs are used, antihypertensive effects are noticeably reduced due to inhibition of vasodilatory prostaglandin synthesis.

ACE inhibitors and angiotensin II antagonists.
NSAIDs (including acetylsalicylic acid at doses ≥ 3 g/day) and angiotensin II antagonists demonstrate a synergistic effect in reducing glomerular filtration in the kidneys; this effect may be enhanced in patients with impaired renal function. Administration of such combinations in elderly and/or dehydrated patients may lead to acute renal failure due to direct effects on glomerular filtration. Adequate hydration and careful monitoring of renal function should be ensured after initiation of concomitant therapy. Additionally, concomitant therapy may reduce the antihypertensive effect of ACE inhibitors and angiotensin II antagonists, resulting in partial loss of efficacy (due to inhibition of vasodilatory prostaglandins).

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

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

Cholestyramine.
Cholestyramine accelerates meloxicam elimination 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.

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

No clinically significant pharmacokinetic drug interactions were observed with concomitant use 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 other 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 continued treatment should be re-evaluated.

Particular attention should be paid to a history of esophagitis, gastritis, and/or peptic ulcer to ensure complete treatment before initiating meloxicam therapy. Close monitoring for possible recurrence should be maintained in patients treated with meloxicam and in those with such history.

Effects on the cardiovascular and cerebrovascular systems.

Careful monitoring is recommended in 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 trials and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and during long-term treatment) may be associated with a small increase in the risk of arterial thrombotic complications (e.g., myocardial infarction and stroke). There are insufficient data to exclude such a risk for meloxicam.

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

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 and in patients with pre-existing cardiovascular disease or cardiovascular risk factors.

Gastrointestinal disorders.

As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without preceding symptoms or a history of serious gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher 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 aspirin or other drugs 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, especially elderly patients, should be informed about any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

Caution should be exercised in patients who are concurrently using medications that may increase the risk of ulceration or bleeding, including heparin (as radical 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. Use of meloxicam in such patients is not recommended (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").

Skin disorders.

Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam use. Patients should be informed about the signs and symptoms of such reactions. The highest risk of such reactions occurs early in treatment, mostly within the first weeks. At the first sign of skin rash, mucosal lesions, or other signs of hypersensitivity, meloxicam should be discontinued. If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking meloxicam, the drug must never be re-administered in the future.

Liver parameters and renal function.

As with most NSAIDs, isolated cases of elevated serum transaminases, increased serum bilirubin, or other liver function parameters, as well as increased serum creatinine, blood urea nitrogen, and other laboratory abnormalities have been reported. In most cases, these abnormalities were mild and transient. If significant or persistent abnormalities are confirmed, meloxicam should be discontinued and follow-up tests performed.

Renal functional 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. Close 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, or diuretics (see section "Interaction with other medicinal products and other forms of interaction");

− hypovolemia (of any origin);

− congestive heart failure;

− renal insufficiency;

− nephrotic syndrome;

− lupus nephritis;

− severe hepatic dysfunction (serum albumin < 25 g/L, or ≥ 10 according to Child-Pugh classification).

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

The dose of meloxicam in patients with end-stage renal disease on dialysis should not exceed 7.5 mg (half of a 15 mg tablet). Dose adjustment is not required in patients with mild to moderate renal impairment (creatinine clearance > 25 mL/min).

Hepatic disorders.

Up to 15% of patients taking NSAIDs may experience 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 of NSAIDs. Rare cases of severe hepatic reactions have also been reported, including jaundice, fulminant fatal hepatitis, liver necrosis, and hepatic failure, some of which were fatal.

Patients with symptoms or suspected hepatic dysfunction, or those with abnormal liver tests, should be evaluated for signs of more severe hepatic impairment during treatment with Algezicam®. If clinical signs and symptoms suggest hepatic disease or if systemic manifestations (e.g., eosinophilia, rash) occur, Algezicam® should be discontinued.

Sodium, potassium, and water retention.

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

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").

Masking of inflammation and fever.

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

Treatment with corticosteroids.

Algezicam® cannot serve as a substitute for corticosteroids in the treatment of corticosteroid insufficiency.

Hematological effects.

Anemia may occur in patients receiving NSAIDs, including Algezicam®. This may be related to fluid retention, gastrointestinal bleeding of unknown origin, macroscopic bleeding, or incompletely described effects on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients undergoing long-term NSAID treatment, including Algezicam®, 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 less, short-term, and reversible. Close monitoring is required in patients taking Algezicam® who may experience adverse effects related to altered platelet function, such as coagulation disorders, or in patients receiving anticoagulants.

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, Algezicam® should not be used in patients hypersensitive to aspirin and should be used with caution in patients with existing asthma.

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.

Anaphylactic reactions.

Anaphylactic reactions may occur with meloxicam, as with other NSAIDs, even in patients without a known reaction to meloxicam. Algezicam® 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 have experienced severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Immediate emergency measures should be taken if an anaphylactoid reaction occurs.

Other warnings.

Adverse reactions are often less tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with other nonsteroidal anti-inflammatory drugs, special caution is required in elderly patients, in whom renal, hepatic, and cardiac dysfunction are common.

Like most NSAIDs, meloxicam may mask symptoms of infectious disease.

Since the product contains lactose, patients with rare hereditary lactose intolerance, galactose intolerance, or glucose-galactose malabsorption should not take this medication.

Use during pregnancy or breastfeeding.

Reproductive function. Meloxicam use may affect reproductive function and is not recommended for women attempting to conceive. Therefore, discontinuation of meloxicam should be considered for women planning pregnancy or undergoing infertility evaluation.**

Pregnancy. Higher than recommended doses may adversely affect pregnancy and/or embryonic and fetal development. Epidemiological data suggest an increased risk of miscarriage. Meloxicam should not be used during the first and second trimesters of pregnancy except when strictly necessary. If a woman is trying to conceive or is using meloxicam during the first or second trimester, the dose and duration of treatment should be as low as possible.

During the third trimester of pregnancy, drugs in the prostaglandin synthesis inhibitor class may cause fetal cardiac toxicity (pulmonary hypertension with premature closure of the arterial duct) and renal failure or may inhibit uterine contractions, leading to delayed or prolonged labor. Therefore, meloxicam is contraindicated during the third trimester of pregnancy.

Lactation. NSAIDs are known to pass into breast milk. Therefore, their use is not recommended in breastfeeding women.

Ability to influence reaction speed when driving or operating machinery.

No specific studies have been conducted on the effect of the drug on the ability to drive or operate machinery. However, based on the pharmacodynamic profile and observed adverse reactions, it can be assumed that meloxicam has no effect or only a negligible effect on such activities. Nevertheless, patients experiencing visual disturbances, drowsiness, or other central nervous system disorders are advised to refrain from driving or operating machinery.

Method of Administration and Dosage

Administer orally.

The total daily dose of the medicinal product should be taken once daily with water or another liquid, during a meal.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Precautions"). Therapy should be reviewed periodically to assess the patient's need for symptomatic relief and response to treatment.

Acute exacerbation of osteoarthritis: 7.5 mg/day (half of a 15 mg tablet). If necessary, the dose may be increased to 15 mg/day.

Rheumatoid arthritis, ankylosing spondylitis: 15 mg/day. The dose may be reduced to 7.5 mg (half of a 15 mg meloxicam tablet) per day, depending on the therapeutic response.

The maximum recommended daily dose is 15 mg of meloxicam.

Special patient populations

Elderly patients and patients with increased risk of adverse reactions

The recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg per day ( half of a 15 mg tablet) . Patients at increased risk of adverse reactions should start treatment with 7.5 mg ( half of a 15 mg tablet)

• per day* (see section "Special Precautions") .

Renal impairment

For patients with severe renal impairment undergoing dialysis, the dose should not exceed 7.5 mg ( half of a 15 mg tablet) per day. Dosage adjustment is not required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 mL/min). For patients with severe renal impairment not undergoing dialysis, see section "Contraindications".

Hepatic impairment

Dosage adjustment is not required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".

Children

Not recommended for use in children under 16 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 elevated blood pressure, acute renal failure, hepatic dysfunction, respiratory depression, coma, seizures, cardiovascular failure, and cardiac arrest. Anaphylactic reactions have been reported during therapeutic use of NSAIDs and may also occur in cases of overdose.

In the event of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown that administration of 4 oral doses of cholestyramine 3 times daily accelerates the elimination of meloxicam.

Adverse reactions.

Edema, arterial hypertension, and heart failure have been observed during treatment with NSAIDs.

Data from studies and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and during prolonged treatment) may be associated with a small increased risk of thrombotic vascular events (e.g., myocardial infarction or stroke) (see section "Special precautions for use").

Most observed adverse effects are gastrointestinal in origin. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special 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 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 precautions for use").

Criteria for assessing the frequency of adverse drug 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); not known (cannot be estimated from available data).

Blood and lymphatic system disorders:

Uncommon – anemia;

Rare – blood test abnormalities (including changes in white blood cell count), leukopenia, thrombocytopenia;

Very rare – agranulocytosis (see "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.

Cardiovascular disorders:

Rare – palpitations;

Heart failure associated with NSAID treatment has been reported;

Uncommon – increased blood pressure, 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, belching;

Rare – colitis, gastroduodenal ulcer, esophagitis;

Very rare – gastrointestinal perforation;

Not known – pancreatitis.

Gastrointestinal bleeding, ulceration, or perforation may be severe and potentially fatal, particularly in elderly patients (see section "Special precautions for use").

Hepatobiliary disorders:

Uncommon – liver function abnormalities (e.g., elevated transaminase or bilirubin levels);

Very rare – hepatitis;

Not known – jaundice, hepatic failure.

Skin and subcutaneous tissue disorders:

Uncommon – angioedema, pruritus, rash;

Rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria;

Very rare – bullous dermatitis, erythema multiforme;

Not known – photosensitivity reactions, exfoliative dermatitis.

Renal and urinary disorders:

Uncommon – sodium and water retention, hyperkalemia (see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction"), changes in renal function parameters (increased serum creatinine and/or urea);

Very rare – acute renal failure, particularly in patients with risk factors (see section "Special 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.

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 medicinal product but generally recognized as 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 precautions for use").