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

Composition:

Active substance: meloxicam;

1 ml of the preparation contains meloxicam equivalent to 100% substance 10 mg;

Excipients: meglumine (N-methylglucamine), glycine, poloxamer 188, glycofurol, sodium chloride, 0.1 M sodium hydroxide solution, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: transparent yellow or greenish-yellow liquid.

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

ATC code M01A C06.

Pharmacological properties.

Pharmacodynamics.

Rheumoxicam® is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, possessing anti-inflammatory, analgesic, and antipyretic effects.

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

Pharmacokinetics.

Absorption. Meloxicam is completely absorbed after intramuscular injection. Relative bioavailability compared to oral administration is nearly 100%. Therefore, dose adjustment is not required when switching from intramuscular to oral administration. After intramuscular injection of 15 mg, maximum plasma concentration reaches approximately 1.6–1.8 μg/mL and is achieved within 1–6 hours.

Distribution. Meloxicam is highly bound to plasma proteins, primarily to albumin (99%). Meloxicam penetrates into synovial fluid, where its concentration is about half that in plasma. The volume of distribution is low, averaging 11 L after intramuscular or intravenous administration, with individual variations within 7–20%. The volume of distribution after multiple oral doses of meloxicam (7.5 to 15 mg) is 16 L, with a coefficient of variation ranging from 11% to 32%.

Biological transformation. Meloxicam undergoes extensive biotransformation in the liver.

Four different metabolites of meloxicam, which are pharmacodynamically inactive, have been identified in urine. The main metabolite, 5’-carboxymeloxicam (60% of dose), is formed via oxidation of the intermediate metabolite 5’-hydroxymethylmeloxicam, which is also excreted but to a lesser extent (9% of dose). In vitro studies suggest that CYP 2C9 plays a major role in the metabolic process, whereas CYP 3A4 isoenzymes play a minor role. Peroxidase activity in patients may be responsible for the formation of two other metabolites, accounting for 16% and 4% of the administered dose, respectively.

Elimination. Elimination of meloxicam occurs primarily as metabolites, excreted in equal parts in urine and feces. Less than 5% of the daily dose is excreted unchanged in feces, and a negligible amount is excreted in urine. The elimination half-life ranges from 13 to 25 hours, depending on the route of administration (oral, intramuscular, or intravenous). Plasma clearance is approximately 7–12 mL/min after a single oral dose, intravenous, or rectal administration.

Dose linearity. Meloxicam exhibits linear pharmacokinetics within the therapeutic dose range of 7.5 mg to 15 mg following both oral and intramuscular administration.

Special patient groups.

Patients with hepatic/renal impairment. Mild to moderate hepatic and renal impairment do not significantly affect the pharmacokinetics of meloxicam. Patients with moderate renal impairment had significantly higher total clearance. Reduced plasma protein binding was observed in patients with end-stage renal disease. In end-stage renal disease, increased volume of distribution may lead to increased free meloxicam concentration. Daily dose should not exceed 7.5 mg (see section "Dosage and administration").

Elderly patients. In elderly male patients, mean pharmacokinetic parameters are similar to those in young male volunteers. In elderly female patients, AUC values are higher and elimination half-life is longer compared to corresponding values in young volunteers of both sexes. Mean plasma clearance at steady state in elderly patients was slightly lower than in young volunteers.

Clinical characteristics.

Indications.

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

Contraindications.

− Hypersensitivity to meloxicam or any of the excipients of the medicinal product, or to active substances with a 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;

− gastrointestinal bleeding or perforation related to previous NSAID therapy, in medical history;

− active or recurrent peptic ulcer/hemorrhage in medical history (two or more separate confirmed episodes of ulcer or bleeding);

− severe hepatic impairment;

− severe renal impairment without dialysis;

− gastrointestinal bleeding, cerebrovascular bleeding in medical history, or other coagulation disorders;

− haemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration);

− severe heart failure;

− treatment of perioperative pain in coronary artery bypass grafting (CABG);

− III trimester of pregnancy (see section ↔Use in pregnancy or lactation≈);

− patient age under 18 years.

Interaction with other medicinal products and other forms of interaction.

Studies on interactions have been conducted only in adults.

Risks associated with hyperkalemia.

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

Pharmacodynamic interactions.

Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/day. Combination with other NSAIDs is not recommended (see section «Special precautions for use»), including acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose.

Glucocorticoids (e.g. corticosteroids). Concomitant use with glucocorticoids requires caution due to an increased risk of bleeding or gastrointestinal ulceration.

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

In other cases (e.g., prophylactic doses), heparin use requires caution due to an increased risk of bleeding.

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 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 drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should receive adequate hydration, and renal function should be monitored after initiation of combined therapy and periodically thereafter (see section «Special precautions for use»).

Other antihypertensive agents (e.g., beta-blockers). As with the above-mentioned drugs, a reduction in the antihypertensive effect of beta-blockers may occur (due to inhibition of vasodilatory prostaglandins).

Calcineurin inhibitors (e.g., cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be enhanced by NSAIDs through mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Careful monitoring of renal function is recommended, especially in elderly patients.

Deferasirox. Concomitant use of meloxicam and deferasirox 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 are available for NSAIDs increasing plasma lithium concentrations (by reducing renal lithium excretion), 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. 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, including those with impaired renal function. If combination therapy is required, blood parameters and renal function should be monitored. Caution is advised if NSAID and methotrexate administration lasts 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 above and section «Adverse reactions»).

Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), meloxicam administration should be withheld for 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 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 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).

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

Cholestyramine accelerates the elimination of meloxicam by disrupting enterohepatic circulation, thus increasing meloxicam clearance by 50% and reducing its 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 (sulfonylurea derivatives, 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 in combination with medicinal products such as oral antidiabetics (sulfonylurea derivatives, nateglinide); this interaction 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 interaction was observed with concomitant administration of antacids, cimetidine, or digoxin.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary for treatment (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 insufficient, 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 should not be used 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. Close monitoring is required for recurrence 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, regardless of prior symptoms or serious gastrointestinal disorders in history.

The risk of gastrointestinal bleeding, ulceration, or perforation is higher with increased 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. Concomitant therapy with protective agents (such as misoprostol or proton pump inhibitors) may be considered for these patients. This also applies to 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 disorders, especially elderly patients, should be informed about any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

The use of meloxicam is not recommended in patients who are concurrently using drugs that increase the risk of ulceration or bleeding, such as heparin, anticoagulants (e.g., warfarin), or other nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid at anti-inflammatory doses (≥ 500 mg per dose or ≥ 3 g total daily dose), or as radical therapy or in geriatric practice (see section "Interaction with other medicinal products and other forms of interaction").

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

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

Hepatic disorders.

Up to 15% of patients treated with NSAIDs (including Revmoxicam®) may experience elevation of one or more liver function tests. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Marked elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (approximately 3 times or more above the upper limit of normal) were observed in 1% of patients during clinical trials with NSAIDs. Additionally, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported during clinical trials with NSAIDs.

Patients with symptoms of hepatic dysfunction or abnormal liver tests should be evaluated for signs of more severe hepatic failure during Revmoxicam® therapy. If clinical symptoms suggest liver disease or systemic manifestations (e.g., eosinophilia, rash) occur, Revmoxicam® should be discontinued.

Cardiovascular disorders.

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

Clinical monitoring of blood pressure at the beginning of meloxicam therapy is recommended for patients with cardiovascular risk factors.

Clinical trial data and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and during long-term treatment) is associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There is insufficient data to exclude such risk with meloxicam use.

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

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

Skin disorders.

Life-threatening severe skin reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis, have been reported with meloxicam use. Patients should be informed about 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 of Stevens–Johnson syndrome or toxic epidermal necrolysis (e.g., progressive skin rash, often with blisters or mucosal involvement), meloxicam treatment must be discontinued. Early diagnosis and discontinuation of any drug that may cause severe skin reactions are crucial for a better prognosis in severe skin reactions. Meloxicam must not be re-administered in the future if a patient has experienced Stevens–Johnson syndrome or toxic epidermal necrolysis during its use.

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

Potential cross-reactivity may occur with other oxicams.

Anaphylactic reactions.

As with other NSAIDs, anaphylactic reactions may occur in patients without known hypersensitivity to Revmoxicam®. Revmoxicam® 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 anaphylactic reaction occurs.

Liver parameters and renal function.

As with most NSAIDs, isolated cases of elevated serum transaminases, serum bilirubin, or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory 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.

Functional renal impairment.

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

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

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

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

Sodium, potassium, and water retention.

NSAIDs may enhance sodium, potassium, and water retention and 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 develop or worsen in susceptible patients. Therefore, clinical monitoring is recommended for patients at risk of sodium, potassium, and water retention (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"). 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 interrupted for at least 5 days before, on the day of, and for at least 2 days after pemetrexed administration (see section "Interaction with other medicinal products and other forms of interaction").

Other warnings and safety measures.

Adverse reactions are 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. Elderly patients have a higher frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "Dosage and administration").

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

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

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

Masking of inflammation and fever.

The pharmacological action of Revmoxicam® in reducing fever and inflammation may complicate diagnosis in suspected non-infectious pain syndromes.

Concomitant corticosteroid therapy.

Revmoxicam® cannot be considered a substitute for corticosteroids in the treatment of corticosteroid deficiency.

Hematological effects.

Anemia may occur in patients receiving NSAIDs, including Revmoxicam®. 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 therapy, including Revmoxicam®, if symptoms 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, transient, and reversible. Close monitoring is required for patients receiving Revmoxicam® who may have adverse effects on platelet function, such as coagulation disorders, and 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, Revmoxicam® should not be used in patients hypersensitive to aspirin and should be used with caution in patients with asthma.

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

Use during pregnancy or 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, discontinuation of meloxicam should be considered for women planning pregnancy or undergoing infertility evaluation.

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

From the 20th week of pregnancy, meloxicam use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, cases of arterial duct constriction after second-trimester treatment have been reported, most of which resolved after treatment discontinuation. Therefore, meloxicam should not be used during the first and second trimesters of pregnancy, except in cases of urgent medical need. For women attempting to conceive or during the first and second trimesters of pregnancy, the dosage and duration of meloxicam treatment should be as low as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after meloxicam exposure for several days starting from the 20th gestational week. Revmoxicam® treatment should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

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

Risks in late pregnancy for mother and newborn:

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

Therefore, meloxicam is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Although specific data on Revmoxicam® are lacking, NSAIDs are known to pass into breast milk. Therefore, use is not recommended for women who are breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

No specific studies on the effect of the medicinal product on the ability to drive a vehicle or operate machinery have been conducted. Based on the pharmacodynamic profile and observed adverse reactions, meloxicam is unlikely to affect or has 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 or operating machinery.

Method of Administration and Dosage.

Dosing.

One injection of 15 mg once daily.

DO NOT EXCEED THE DOSE OF 15 mg/DAY.

Treatment should be limited to one injection at the beginning of therapy; the maximum duration of treatment is up to 2–3 days in justified exceptional cases (e.g., when oral and rectal routes of administration are not feasible). Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Precautions").

The patient's need for symptomatic relief and response to treatment should be periodically evaluated.

Special Patient Categories.

Elderly patients (see section "Pharmacokinetics")

The recommended dose for elderly patients is 7.5 mg per day (half of a 1.5 ml ampoule) (also see section "Method of Administration and Dosage" – "Patients at Increased Risk of Adverse Reactions" and section "Special Precautions").

Patients at Increased Risk of Adverse Reactions (see section "Special Precautions")

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

Renal Impairment

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

For patients with end-stage renal disease undergoing hemodialysis, the dose should not exceed 7.5 mg per day (half of a 1.5 ml ampoule).

Dose reduction is not required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 ml/min).

Hepatic Impairment

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

Method of Administration.

For intramuscular use.

The drug should be administered slowly by deep intramuscular injection into the upper outer quadrant of the buttock, strictly observing aseptic technique. In case of repeated administration, it is recommended to alternate between left and right buttocks. Prior to injection, it is important to ensure that the needle tip is not within a blood vessel.

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

If the patient has a hip prosthesis, the injection should be administered into the opposite buttock.

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

Children.

Rheumoxicam® 15 mg/1.5 ml solution for injection is contraindicated in children (under 18 years of age).

Overdose.

Symptoms.

Symptoms of acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding may occur. Severe poisoning may lead to arterial hypertension, acute renal failure, 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 overdose.

Management.

In case of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown that meloxicam elimination is accelerated by administering 4 oral doses of cholestyramine 3 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) is associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke) (see section "Special Warnings and Precautions for Use").

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

Most of the adverse 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"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported following administration (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.

There have been reports of severe skin reactions: Stevens–Johnson syndrome and toxic epidermal necrolysis (see section "Special Warnings and Precautions for Use").

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

Immune system disorders:

Uncommon – allergic reactions, excluding anaphylactic or anaphylactoid reactions;

Not known – anaphylactic shock, 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 use has been reported.

Vascular disorders:

Uncommon – increased blood pressure (see section "Special Warnings and Precautions for Use"), flushing.

Respiratory, thoracic and mediastinal disorders:

Rare – asthma in patients with aspirin or other NSAID allergy;

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;

Not known – pancreatitis.

Gastrointestinal bleeding, ulcers, or perforation may be severe and potentially fatal, particularly in elderly patients (see section "Special Warnings and Precautions for Use").

Hepatobiliary disorders:

Uncommon – abnormalities in liver function tests (e.g., increased transaminases or bilirubin);

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 (increased serum creatinine and/or urea);

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.

Reproductive system and breast disorders:

Not known – female infertility, ovulation delay.

General disorders and administration site conditions:

Common – injection site induration, injection site pain;

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 receiving meloxicam and other potentially myelotoxic medicinal products (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Adverse reactions not associated with the use of the drug but typical for other compounds of the class.

Renal parenchymal injury, 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 authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

4 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature between 8°C and 25°C.

Keep out of the reach and sight of children.

Packaging.

1.5 ml in an ampoule. 3 or 5 ampoules in a blister. 1 blister in a carton. Or 5 ampoules in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Address of the manufacturer and location of its business operations.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.

Revmoxykam®