Melbek
Ukraine
Table of Contents
INSTRUCTIONS for medical use of the medicinal product MELBEK® (MELBEK®)
Composition:
Active substance: meloxicam;
1 ampoule (1.5 ml) of the preparation contains 15 mg of meloxicam;
Excipients: meglumine, glycofural, poloxamer 188, glycine, sodium chloride, sodium hydroxide or hydrochloric acid, water for injections.
Pharmaceutical form. Solution for injection.
Main physicochemical characteristics: clear yellow-colored solution.
Pharmacotherapeutic group.
Non-steroidal anti-inflammatory and antirheumatic agents.
ATC code M01A C06.
Pharmacological properties.
Pharmacodynamics.
Melbek® 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. The relative bioavailability compared to oral administration is nearly 100%. Therefore, dose adjustment is not required when switching from intramuscular to oral administration. After an intramuscular injection of 15 mg, the 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 (7.5–15 mg) is 16 L, with a coefficient of variation ranging from 11% to 32%.
Biological transformation. Meloxicam undergoes extensive biotransformation in the liver.
Four different metabolites of meloxicam, pharmacodynamically inactive, have been identified in urine. The main metabolite, 5’-carboxymeloxicam (60% of dose), is formed via oxidation of the intermediate metabolite 5’-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of dose). In vitro studies suggest that CYP2C9 plays a major role in the metabolic process, 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. Meloxicam is excreted primarily as metabolites in equal proportions via 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 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 showed significantly higher total clearance. Reduced plasma protein binding has been observed in patients with end-stage renal disease. In end-stage renal disease, increased volume of distribution may lead to higher concentrations of free meloxicam. The daily dose should not exceed 7.5 mg (see section "Dosage and administration").
Elderly patients. Pharmacokinetic parameters in elderly male patients are similar to those in younger patients. In elderly female patients, AUC values are higher and elimination half-life is longer compared to younger patients of either sex. Mean plasma clearance at steady state in elderly patients was slightly lower than in younger volunteers.
Clinical characteristics.
Indications.
Short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when oral and rectal routes of administration cannot be used.
Contraindications.
− Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
− Patient age under 18 years;
− Hypersensitivity to meloxicam or to any excipients of the medicinal product, or to active substances with similar actions, such as NSAIDs, acetylsalicylic acid. Meloxicam should not be administered to patients who have experienced asthma symptoms, nasal polyps, angioedema, or urticaria after taking acetylsalicylic acid or other NSAIDs;
− Gastrointestinal bleeding or perforation related to previous NSAID therapy in medical history;
− Active or recurrent peptic ulcer/bleeding in 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;
− Hemostasis 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).
Interaction with other medicinal products and other forms of interaction.
Studies on interactions were conducted only in adults.
Risks associated with hyperkalemia
Certain medicinal products or therapeutic groups may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (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 the presence of associated factors. The risk of developing 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"), as well as acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose.
Glucocorticoids (e.g., corticosteroids). 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 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. 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), caution is required when using heparin due to an increased risk of bleeding.
Thrombolytic and antiplatelet agents. Increased risk of bleeding through inhibition of platelet function and damage to the gastroduodenal mucosa.
Selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors or angiotensin II antagonists and medicinal products 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 concomitant therapy and periodically thereafter (see section "Special precautions for use").
Other antihypertensive medicinal products (e.g., beta-blockers). As with the use of the below-mentioned medicinal products, a reduction in the antihypertensive effect of beta-blockers may occur (due to inhibition of vasodilatory prostaglandins).
Calcineurin inhibitors (e.g., cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be enhanced by NSAIDs through mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Careful monitoring of renal function is recommended, especially in elderly patients.
Deferasirox.
Concomitant use of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these medicinal products.
Pharmacokinetic interaction: effect of meloxicam on the pharmacokinetics of other medicinal products.
Lithium. Data exist for NSAIDs increasing plasma lithium concentrations (by reducing renal excretion of lithium), which may reach toxic levels. Concomitant use of lithium and NSAIDs is not recommended (see section "Special precautions for use"). If combination therapy is necessary, plasma lithium levels should be closely monitored at the beginning of treatment, during dose adjustment, and upon discontinuation of meloxicam therapy.
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 (more than 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 should be exercised if NSAID and methotrexate administration continues for 3 consecutive days, as plasma methotrexate levels may increase and enhance toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, hematological toxicity of methotrexate may increase during NSAID treatment (see above) (see section "Adverse reactions").
Pemetrexed. When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance from 45 to 79 mL/min), meloxicam administration should be withheld for 5 days before pemetrexed infusion, on the day of infusion, and for 2 days after 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 adverse reactions associated with pemetrexed. 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.
No clinically significant pharmacokinetic 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 NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Meloxicam should not be used for the treatment of patients requiring relief of acute pain.
If there is no improvement 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 their complete treatment before starting meloxicam therapy. Patients treated with meloxicam and those with such history should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without previous symptoms or serious gastrointestinal disorders in history.
The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher doses of the drug in patients with a history of peptic ulcer, especially complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should start treatment with the lowest effective dose. For these patients, combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid or other drugs that increase gastrointestinal risks (see information below and section "Interaction with other medicinal products and other forms of interaction").
Patients with a history of gastrointestinal toxicity, especially elderly patients, should be informed about any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.
Concomitant use of meloxicam is not recommended in patients taking drugs that may increase the risk of ulceration or bleeding, such as heparin, as radical therapy or in geriatric practice, anticoagulants such as warfarin or other nonsteroidal anti-inflammatory drugs, or acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose (see section "Interaction with other medicinal products and other forms of interaction").
If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may worsen (see section "Adverse reactions").
Hepatic disorders.
Up to 15% of patients taking NSAIDs (including Melbex®) may experience elevated levels of one or more liver function tests. These laboratory abnormalities may progress, remain unchanged, or be transient during continued treatment. Significant increases in ALT or AST (approximately three times or more above normal) were observed in 1% of patients during clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, liver necrosis and liver failure, some of which were fatal, have been reported during clinical trials with NSAIDs.
Patients with symptoms and/or signs of hepatic dysfunction or those who have experienced abnormal liver function tests should be evaluated for the development of more severe hepatic failure during treatment with Melbex®. If clinical signs and symptoms are consistent with the development of liver disease or if systemic manifestations of disease (e.g., eosinophilia, rash, etc.) are observed, use of Melbex® 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.
Patients with risk factors should have clinical monitoring of blood pressure at the beginning of therapy, especially at the start of meloxicam treatment.
Data from studies and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and with prolonged treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There is insufficient data to exclude such a risk for meloxicam.
Therapy with meloxicam in patients with uncontrolled arterial hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be initiated only after careful evaluation. Such evaluation is necessary before starting long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smokers).
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. The risk increases with duration of use. Patients with cardiovascular disease or cardiovascular risk factors may have an increased risk of thrombotic complications.
Skin disorders.
Life-threatening severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with meloxicam use. Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored for skin reactions. The highest risk of Stevens-Johnson syndrome or toxic epidermal necrolysis occurs during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., progressive skin rash often with blisters or mucosal involvement), meloxicam treatment should be discontinued. It is important to diagnose promptly and discontinue any drugs that may cause severe skin reactions: Stevens-Johnson syndrome or toxic epidermal necrolysis. This is associated with a better prognosis in severe skin reactions. If a patient has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while using meloxicam, the drug must not be restarted at any time in the future.
Cases of fixed drug eruption have been reported with meloxicam use. Meloxicam should not be re-administered to patients who have had a history of fixed drug eruption associated with meloxicam use. Potential cross-reactivity may occur with other oxicams.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients without known sensitivity to meloxicam. Melbex® 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. Emergency measures should be taken if an anaphylactic reaction is detected.
Liver parameters and kidney function.
As with treatment with most NSAIDs, isolated cases of elevated serum transaminases, serum bilirubin, or other liver function parameters, elevated serum creatinine and blood urea nitrogen, as well as other laboratory parameter abnormalities have been described. In most cases, these abnormalities were mild and transient. If significant or persistent abnormalities are confirmed, meloxicam use should be discontinued and follow-up tests performed.
Functional renal failure.
NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, may induce functional renal failure by decreasing glomerular filtration. This adverse effect is dose-dependent. Careful monitoring of diuresis and renal function is recommended at the beginning of treatment or after dose increase in patients with the following risk factors:
− advanced age;
− concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other forms of interaction");
− hypovolemia (of any origin);
− congestive heart failure;
− renal failure;
− nephrotic syndrome;
− lupus nephritis;
− severe hepatic dysfunction (serum albumin < 25 g/L or ≥ 10 according to Child-Pugh classification).
In isolated cases, NSAIDs may lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndromes.
The dose of meloxicam in patients with end-stage renal failure on dialysis should not exceed 7.5 mg. Dose adjustment is not required in patients with mild to moderate renal impairment (creatinine clearance > 25 mL/min).
Sodium, potassium, and water retention.
NSAIDs may enhance sodium, potassium, and water retention and affect the natriuretic effects of diuretics. In addition, a reduction in the antihypertensive effect of antihypertensive drugs may occur (see section "Interaction with other medicinal products and other forms of interaction"). As a result, edema, heart failure, or arterial hypertension may be accelerated or exacerbated in susceptible patients. Therefore, clinical monitoring is recommended for patients at risk of sodium, potassium, and water retention (see sections "Dosage and administration" and "Contraindications").
Hyperkalemia.
Hyperkalemia may be promoted by diabetes mellitus or concomitant use of drugs that increase potassium levels (see section "Interaction with other medicinal products and other forms of interaction"). In such cases, potassium levels should be monitored regularly.
Combination with pemetrexed.
In patients with mild to moderate renal impairment receiving pemetrexed, meloxicam treatment should be withheld for at least 5 days before, on the day of, and for at least 2 days after pemetrexed administration (see section "Interaction with other medicinal products and other forms of interaction").
Other warnings and safety measures.
Adverse reactions are often worse tolerated in elderly, debilitated, or weakened patients, who require careful monitoring. As with treatment with other NSAIDs, caution is required in elderly patients, in whom decreased renal, hepatic, and cardiac function is more likely. Elderly patients have a higher frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can 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, like any other NSAID, may negatively affect reproductive function and is not recommended for women who wish 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").
The medicinal product contains less than 1 mmol of sodium (23 mg) per 1.5 mL vial, i.e., is essentially sodium-free.
Masking of inflammation and fever.
The pharmacological action of meloxicam, aimed at reducing fever and inflammation, may reduce the diagnostic value of these signs in identifying complications related to suspected non-infectious painful conditions.
Glucocorticoid therapy.
Melbex® cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may occur in patients receiving NSAIDs, including Melbex®. This may be related to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients undergoing long-term treatment with NSAIDs, including Melbex®, if symptoms and signs of anemia are present.
NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, short-term, and reversible. Patients receiving Melbex® who may have adverse effects related to changes in platelet function, such as coagulation disorders, or patients receiving anticoagulants, require careful monitoring.
Use in patients with asthma.
Patients with asthma may have aspirin-sensitive asthma. Use of aspirin 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, Melbex® should not be used in patients sensitive to aspirin and should be used with caution in patients with asthma.
Use during pregnancy or breastfeeding.
Fertility. Meloxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may negatively affect reproductive function and is not recommended for women who wish to become pregnant. Therefore, for women planning pregnancy or undergoing infertility evaluation, discontinuation of meloxicam use should be considered.
Pregnancy. Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and development of cardiac defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac defects increased from less than 1% to about 1.5%. This risk is believed to increase with higher doses and longer duration of treatment.
From the 20th week of pregnancy, use of meloxicam may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after discontinuation of treatment. Therefore, meloxicam should not be used during the first and second trimesters of pregnancy, except in cases of urgent need. If a woman trying to conceive or during the first and second trimesters of pregnancy uses meloxicam, the dose and duration of treatment should be as low as possible.
Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after meloxicam exposure for several days starting from the 20th gestational week. Use of meloxicam 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 (see above).
Risks for the mother in late pregnancy and the newborn:
− potential for prolonged bleeding time, anti-aggregatory effect even at very low doses;
− inhibition of uterine contractions leading to delayed or prolonged labor.
Therefore, meloxicam is contraindicated during the third trimester of pregnancy.
Breastfeeding. Although specific data on the use of meloxicam are lacking, it is known that NSAIDs can 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 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 effect or only a minor effect on such activities. Nevertheless, patients who experience visual disturbances, including blurred vision, dizziness, somnolence, vertigo, or other central nervous system disorders, are advised to refrain from driving a vehicle or operating machinery.
Method of Administration and Dosage
Intramuscular use.
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, with a maximum duration of up to 2–3 days only in justified exceptional cases (e.g., when oral and rectal routes of administration are not feasible). Adverse reactions may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Instructions").
The patient's need for symptomatic relief and response to treatment should be periodically evaluated.
Special patient populations
Elderly patients and patients at increased risk of adverse reactions
The recommended dose for elderly patients is 7.5 mg per day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg per day (half of a 1.5 ml vial) (see section "Special Instructions").
Renal impairment
For patients with severe renal impairment undergoing dialysis, the dose should not exceed 7.5 mg per day (half of a 1.5 ml vial).
Dose adjustment is not required in patients with moderate to mild 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
Dose reduction is not required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".
Method of administration
The medication should be administered slowly via deep intramuscular injection into the upper outer quadrant of the buttock, strictly following aseptic technique. When repeated injections are necessary, alternating between left and right buttocks is recommended. Prior to injection, it is important to ensure that the needle tip has not entered a blood vessel.
The injection should be stopped immediately if severe pain occurs during administration.
In the presence of a hip prosthesis, the injection should be administered into the opposite buttock.
Children
Melbek® 15 mg/1.5 ml solution for injection is contraindicated in children (under 18 years of age) (see section "Contraindications").
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, 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.
In cases of NSAID overdose, symptomatic and supportive measures are recommended for patients. Studies have shown accelerated elimination of meloxicam using 4 oral doses of cholestyramine administered 3 times daily.
Adverse Reactions
Data from clinical trials and epidemiological studies 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 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 exacerbation of colitis and Crohn’s disease have been reported after administration (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.
Serious skin reactions have been reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis (see section "Special Warnings and Precautions for Use").
Blood and lymphatic system disorders: anemia, 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: allergic reactions, including anaphylactic or anaphylactoid reactions, anaphylactic shock, anaphylactic reaction; anaphylactoid reaction, including shock.
Psychiatric disorders: mood changes, nightmares, confusion, disorientation, insomnia.
Nervous system disorders: headache, dizziness, somnolence.
Eye disorders: visual disturbances including blurred vision; conjunctivitis.
Ear and labyrinth disorders: dizziness, tinnitus.
Cardiac disorders: palpitations.
Heart failure associated with NSAID use has been reported.
Vascular disorders: increased blood pressure (see section "Special Warnings and Precautions for Use"), flushing.
Respiratory, thoracic and mediastinal disorders: asthma in patients with aspirin or other NSAID allergy; upper respiratory tract infections, cough.
Gastrointestinal disorders: gastrointestinal disturbances: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea, occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, eructation, colitis, gastroduodenal ulcer, esophagitis, gastrointestinal perforation, pancreatitis.
Gastrointestinal bleeding, ulceration, or perforation may be severe and potentially fatal, especially in elderly patients (see section "Special Warnings and Precautions for Use").
Hepatobiliary disorders: abnormalities in liver function tests (e.g., elevated transaminases or bilirubin), hepatitis, jaundice, liver failure.
Skin and subcutaneous tissue disorders: angioneurotic edema, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, bullous dermatitis, erythema multiforme, photosensitivity reactions, exfoliative dermatitis, fixed drug eruption (see section "Special Warnings and Precautions for Use").
Renal and urinary disorders: 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), acute renal failure, particularly in patients with risk factors (see section "Special Warnings and Precautions for Use"), urinary tract infections, altered micturition frequency.
General disorders and administration site conditions: injection site induration, injection site pain, edema including peripheral edema, influenza-like symptoms.
Musculoskeletal and connective tissue disorders: arthralgia, back pain, joint signs and symptoms.
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 generally recognized as typical for other compounds in 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").
Shelf life. 4 years.
Storage conditions.
Store in a light-protected place at a temperature not exceeding 25 °C.
Keep out of reach and sight of children.
Incompatibilities.
Due to possible incompatibility, Melbek® (injection solution) must not be mixed with other medicinal products in the same syringe.
Packaging.
1.5 ml in 2 ml ampoules. 3 ampoules per cardboard pack.
Prescription category.
Prescription only.
Manufacturer.
Idol Ilac Dolulm Sanayi Ve Ticaret A.S.
Manufacturer's address and place of business.
Davutpasa Cadessi Cebelik Bey Sokak No 20 Topkapi Zeytinburnu Istanbul, Turkey.