Instructions for Melbek tablets 15 mg blister No. 30
Composition
active ingredient: meloxicam;
1 tablet contains meloxicam 7.5 mg or 15 mg;
Excipients: crospovidone, povidone, microcrystalline cellulose, sodium citrate, anhydrous lactose, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
7.5 mg tablets: round, light yellow tablets with a score on one side;
15 mg tablets: round, light yellow tablets with a cross-shaped score on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Oxycodone. ATX code M01A C06.
Pharmacological properties
Pharmacodynamics.
Meloxicam belongs to the nonsteroidal anti-inflammatory drugs of the oxicam group, a selective COX-2 inhibitor containing enolic acid in its structure; it has anti-inflammatory, analgesic and antipyretic effects. The mechanism of action of the drug is its ability to inhibit the biosynthesis of prostaglandins, which are mediators of inflammation, due to the selective inhibition of COX-2.
The mechanism of action is associated with selective inhibition of COX-2 compared to COX-1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with inhibition of COX-2 synthesis, while inhibition of COX-1 leads to toxic damage to the stomach and kidneys. Compared with non-selective COX inhibitors, meloxicam rarely causes side effects from the gastrointestinal tract and kidneys. Meloxicam does not affect platelet aggregation and bleeding time.
Pharmacokinetics.
Absorption.
Meloxicam is well absorbed from the gastrointestinal tract regardless of food intake. The bioavailability of the drug is 89%. The equilibrium concentration is reached on the 3rd-5th day of treatment. Long-term administration of the drug (more than 6 months) does not cause an increase in its concentration in the blood plasma compared to the indicators at the beginning of use.
Distribution.
Approximately 99% of the drug is bound to plasma proteins. Meloxicam penetrates into the synovial fluid, where its concentration is approximately half that in plasma. The volume of distribution is on average 11 l.
Metabolism.
Biotransformation occurs in the liver by oxidation of methyl groups with the formation of 4 inactive metabolites.
Elimination (extraction).
Meloxicam is excreted mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged in the feces, a small amount in the urine. The half-life of the drug is 20 hours.
Plasma clearance is 8 ml/min, decreasing in the elderly.
Indication
Short-term symptomatic treatment of exacerbations of osteoarthritis.
Long-term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis.
Contraindication
- Hypersensitivity to meloxicam or to any of the other ingredients of the medicinal product, to active substances with similar effects, such as NSAIDs, acetylsalicylic acid. Meloxicam should not be prescribed to patients who have experienced symptoms of asthma, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs;
- 3rd trimester of pregnancy;
- patient's age up to 16 years;
- history of gastrointestinal bleeding or perforation associated with previous NSAID therapy;
- history of active or recurrent peptic ulcer/bleeding (two or more separate confirmed episodes of ulceration or bleeding);
- severe liver failure;
- severe renal failure without dialysis;
- gastrointestinal bleeding, history of cerebrovascular bleeding or other blood clotting disorders;
- severe heart failure;
- contraindicated for the treatment of perioperative pain in coronary artery bypass grafting (CABG).
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions.
Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/dose. Combination with other NSAIDs, including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g - single dose or ≥ 3 g - total daily dose) is not recommended.
Corticosteroids (e.g. glucocorticoids): Concomitant use with corticosteroids requires caution due to increased risk of bleeding or ulceration in the digestive tract.
Anticoagulants or heparin used in geriatric practice or at therapeutic doses. 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. The concomitant use of NSAIDs and anticoagulants or heparin in geriatric practice or at therapeutic doses is not recommended.
In other cases, heparin should be used with caution due to the increased risk of bleeding. Careful monitoring of the INR (international normalized ratio) is necessary if the combination is proven to be unavoidable.
Selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors and angiotensin II antagonists. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (such as dehydrated patients or elderly patients with impaired renal function), the 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, the combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and renal function should be monitored after initiation of concomitant therapy and periodically thereafter.
Other antihypertensive drugs (e.g. beta-blockers). As with the following drugs, the antihypertensive effect of beta-blockers may be reduced (due to inhibition of vasodilating prostaglandins).
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus). Nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Close monitoring of renal function is recommended, especially in elderly patients.
Intrauterine contraceptive devices: Reduced effectiveness of intrauterine contraceptive devices has been reported with the use of NSAIDs, but this requires further confirmation.
Pharmacokinetic interaction: the effect of meloxicam on the pharmacokinetics of other drugs.
Lithium. There is evidence that NSAIDs increase the level of lithium in the blood plasma (due to a decrease in the renal excretion of lithium), to toxic values. The simultaneous use of lithium and NSAIDs is not recommended. If combination therapy is necessary, careful monitoring of the content of lithium in the blood plasma should be carried out at the beginning of treatment, during dose adjustment and when stopping treatment with meloxicam.
Methotrexate. NSAIDs may reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high doses of methotrexate (more than 15 mg per week). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low doses of methotrexate, in particular in patients with impaired renal function. If combined treatment is necessary, blood counts and renal function should be monitored. Caution should be exercised if NSAIDs and methotrexate are taken for 3 consecutive days, as the plasma level of methotrexate may increase and toxicity may be increased. Although the pharmacokinetics of methotrexate (15 mg per week) were not affected by concomitant treatment with meloxicam, it should be considered that the haematological toxicity of methotrexate may increase during treatment with NSAIDs (see information above).
Pharmacokinetic interaction: the effect of other drugs on the pharmacokinetics of meloxicam.
Cholestyramine: Cholestyramine accelerates the elimination of meloxicam due to impaired intrahepatic circulation, so the clearance of meloxicam increases by 50% and the half-life decreases to 13±3 hours. This interaction is clinically significant.
No clinically significant pharmacokinetic interaction was found when co-administered with antacids, cimetidine, and digoxin.
Application features
Adverse reactions can be minimised 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 in case of insufficient therapeutic effect, nor should additional NSAIDs be used, as this may increase toxicity while the therapeutic benefit has not been proven. The concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Meloxicam is not used to relieve acute pain.
If there is no improvement after several days of use, the clinical benefits of treatment should be re-evaluated.
Attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer in order to ensure that they are completely cured before starting therapy with meloxicam. Patients treated with meloxicam and patients with a history of such cases should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, especially complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be started at the lowest effective dose. For such patients, as well as for patients requiring concomitant low-dose acetylsalicylic acid or other medicinal products that increase gastrointestinal risks, combination therapy with protective medicinal products (such as misoprostol or proton pump inhibitors) should be considered (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 report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.
Caution should be exercised in patients receiving concomitant medications that increase the risk of ulceration or bleeding, including heparin, as a radical therapy or in geriatric practice, anticoagulants such as warfarin, or other nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g - single dose or ≥ 3 g - total daily dose).
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 diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated.
Liver disorders.
Up to 15% of patients taking NSAIDs (including Melbec®) may have elevated values of one or more liver tests. Such abnormalities may progress, may remain unchanged, or may be transient with continued treatment. Marked increases in ALT or AST (approximately 3 times or more above normal) have been observed in 1% of patients during studies with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant fatal hepatitis, hepatic necrosis, and hepatic failure, some of them fatal, have been reported.
If hepatic dysfunction is suspected or the patient has abnormal liver function tests, the patient should be evaluated for the development of symptoms of more severe hepatic insufficiency during therapy with the drug. If symptoms are consistent with the development of liver disease or if systemic manifestations of the disease (e.g. eosinophilia, rash, etc.) are observed, then the use of Melbek® should be discontinued.
Cardiovascular disorders.
Close 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 reported with NSAID therapy.
In patients with risk factors, monitoring of blood pressure is recommended at the beginning of therapy, especially at the beginning of treatment with meloxicam.
Available data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) is associated with a slightly increased risk of vascular thrombotic events (e.g. myocardial infarction or stroke). There is insufficient data to exclude such a risk with meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with meloxicam only after careful consideration. Such consideration is necessary before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).
NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. The increased risk is related to the duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease are at increased risk.
Skin disorders.
Serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported rarely with NSAIDs. The highest risk of these reactions was observed at the beginning of treatment, with the majority of these reactions occurring within the first month of treatment. Meloxicam should be discontinued at the first appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients with no known reaction to Melbek®. Melbek® should not be used in patients with the aspirin triad. This symptom complex occurs in patients with bronchial asthma who have experienced rhinitis with or without nasal polyps or who have experienced severe, potentially fatal bronchospasm after taking acetylsalicylic acid or other NSAIDs. Emergency care should be taken if an anaphylactoid reaction occurs.
As with most NSAIDs, isolated cases of increased serum transaminases, increased serum bilirubin or other liver function parameters, as well as increased serum creatinine and blood urea nitrogen, and other abnormalities have been reported. In most cases, these abnormalities were minor and transient. In the event of significant or persistent abnormalities, meloxicam should be discontinued and control tests performed.
Functional renal failure.
NSAIDs, by inhibiting the vasodilatory effects of renal prostaglandins, may induce functional renal failure due to decreased glomerular filtration. This adverse effect is dose-dependent. Close monitoring of urine output and renal function is recommended at the beginning of treatment or after dose increases in patients with the following risk factors:
- old age;
- concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics;
- hypovolemia (of any origin);
- congestive heart failure;
- renal failure;
- nephrotic syndrome;
- lupus nephropathy;
- severe hepatic dysfunction (serum albumin < 25 g/l or ≥ 10 according to the Child-Pugh classification).
In rare cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.
The dose of meloxicam for patients with end-stage renal disease on dialysis should not exceed 7.5 mg. In patients with mild to moderate renal impairment, the dose may not be reduced (creatinine clearance greater than 25 ml/min).
Sodium, potassium and water retention.
NSAIDs may increase sodium, potassium and water retention and may interfere with the natriuretic effects of diuretics. In addition, the antihypertensive effect of antihypertensive drugs may be reduced. As a result, edema, heart failure or hypertension may be exacerbated in susceptible patients. Therefore, clinical monitoring is recommended in patients at risk.
Hyperkalemia.
Hyperkalemia may be caused by diabetes mellitus or concomitant use of drugs that increase potassium levels. In such cases, potassium levels should be monitored regularly.
Other warnings and precautions.
Adverse reactions are often worse tolerated in elderly, frail, or debilitated patients who require close monitoring. As with other NSAIDs, caution should be exercised in the elderly, who are more likely to have decreased renal, hepatic, and cardiac function. Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
Meloxicam, like any other NSAID, may mask the symptoms of infectious diseases.
Meloxicam may impair reproductive function and is not recommended in women attempting to conceive. Therefore, discontinuation of meloxicam should be considered in women attempting to conceive or undergoing investigation of infertility.
The drug contains lactose, so this drug is not recommended for patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Masking inflammation and fever.
The pharmacological action of the drug to reduce fever and inflammation may complicate diagnosis in suspected non-infectious pain conditions.
Corticosteroid treatment.
Melbek® cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may occur in patients receiving NSAIDs, including Meloxicam. This may be due to fluid retention, gastrointestinal bleeding of unknown origin, or macroscopic or incompletely described effects on erythropoiesis. Patients receiving long-term treatment with NSAIDs, including meloxicam, should have their hemoglobin or hematocrit monitored if they develop symptoms of anemia.
NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. In contrast to acetylsalicylic acid, their effect on platelet function is quantitatively smaller, short-lived and reversible. Patients taking Melbek® who may have adverse effects on platelet function, including coagulation disorders, and patients receiving anticoagulants should be carefully monitored.
Use in patients with existing asthma.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which may be fatal. Given the cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs, Melbek® should not be used in patients sensitive to aspirin and should be prescribed with caution in patients with bronchial asthma.
Use during pregnancy or breastfeeding
Fertility: Meloxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may have an adverse effect on reproductive function and is not recommended in women attempting to conceive. Therefore, in women planning pregnancy or undergoing investigation of infertility, discontinuation of meloxicam should be considered.
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo-foetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations has increased from less than 1% to approximately 1.5%. This risk is thought to increase with increasing dose and duration of treatment.
During the first and second trimesters of pregnancy, meloxicam should not be used unless clearly necessary. For women attempting to conceive and during the first and second trimesters of pregnancy, the dose and duration of treatment with meloxicam should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors pose a risk to the fetus:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired renal function, which may develop into renal failure with oligohydramnios.
Risks for the mother in the last stages of pregnancy and the newborn;
- possibility of prolongation of bleeding time, anti-aggregation effect even at very low doses;
- suppression of uterine contractions, leading to delayed or prolonged labor.
Therefore, meloxicam is contraindicated during the third trimester of pregnancy.
Breastfeeding: Although there are no specific data on the drug, NSAIDs are known to pass into breast milk. Therefore, use is not recommended in women who are breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no specific studies on the effects of the drug on the ability to drive or use machines. Based on the pharmacodynamic profile and the observed adverse reactions, it can be assumed that meloxicam has no or negligible influence on these activities. However, patients who have experienced visual disturbances, including blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, are advised to refrain from driving or using machines.
Method of administration and doses
It is administered orally.
The total daily amount of the drug should be taken once, washed down with water or other liquid, during meals.
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to control symptoms.
The patient's need for symptomatic relief and response to treatment should be assessed periodically.
Exacerbation of osteoarthritis:
7.5 mg/day (1 tablet of 7.5 mg or half a tablet of 15 mg). If necessary, the dose can be increased to 15 mg/day (1 tablet of 15 mg or 2 tablets of 7.5 mg).
Rheumatoid arthritis, ankylosing spondylitis:
15 mg/day (1 tablet of 15 mg or 2 tablets of 7.5 mg).
See also “Special patient categories”.
Depending on the therapeutic effect, the dose can be reduced to 7.5 mg/day (1 tablet of 7.5 mg or half a tablet of 15 mg).
Do not exceed a dose of 15 mg/day.
Special categories of patients.
Elderly patients and patients at increased risk of developing adverse reactions.
The recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg per day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg per day.
Kidney failure.
For patients with severe renal insufficiency who are on dialysis, the dose should not exceed 7.5 mg per day.
No dose reduction is 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 requiring dialysis, see section 4.3).
Liver failure.
No dose reduction is required in patients with mild to moderate hepatic impairment (for patients with severe hepatic impairment, see section "Contraindications").
Children.
Contraindicated for 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 therapy. Gastrointestinal bleeding may occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic use of NSAIDs, which may also occur with overdose.
In case of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown that meloxicam elimination is accelerated by administration of 4 oral doses of cholestyramine 3 times daily.
Adverse reactions
Available data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) is associated with a somewhat increased risk of vascular thrombotic events (e.g. myocardial infarction or stroke).
Edema, hypertension, and heart failure have been observed with NSAID treatment.
Most of the side effects observed are of gastrointestinal origin. Peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, may occur. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been observed after use. Gastritis has been observed less frequently.
Blood system: anemia, blood count abnormalities (including changes in leukocyte count), leukopenia, thrombocytopenia. Very rare cases of agranulocytosis have been reported.
Immune system disorders: allergic reactions, except anaphylactic or anaphylactoid; anaphylactic reaction, anaphylactoid reaction, including shock.
On the part of the psyche: mood swings, nightmares, confusion, disorientation, insomnia.
From the nervous system: headache, dizziness, drowsiness.
On the part of the organs of vision: visual function disorders, including blurred vision; conjunctivitis.
On the part of the organs of hearing: dizziness, ringing in the ears.
From the cardiovascular system: feeling of palpitations, increased blood pressure, hot flashes.
Heart failure has been reported in association with NSAID treatment.
On the part of the respiratory system: bronchial asthma in patients allergic to acetylsalicylic acid and other NSAIDs, upper respiratory tract infections, cough.
On the part of the digestive tract: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea, occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, belching, colitis, gastroduodenal ulcer, esophagitis, gastrointestinal perforation.
Gastrointestinal bleeding, ulceration or perforation may be severe and potentially fatal, especially in elderly patients.
Hepatobiliary system: abnormal liver function tests (e.g. increased transaminases or bilirubin), hepatitis, jaundice, liver failure.
Skin: angioedema, itching, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, bullous dermatitis, erythema multiforme, photosensitivity reactions, exfoliative dermatitis.
From the urinary system: sodium and water retention, hyperkalemia, changes in renal function (increased creatinine and/or serum urea), acute renal failure, particularly in patients with risk factors, urinary tract infections, urinary frequency disorders.
General disorders: edema, including edema of the lower extremities; flu-like symptoms.
Musculoskeletal system: arthralgia, back pain, joint-related symptoms.
Certain serious and/or common adverse reactions.
Very rare cases of agranulocytosis have been reported in patients treated with meloxicam and other potentially myelotoxic drugs.
Adverse reactions that have not been observed during use of the drug, but which are characteristic of other compounds of the class.
Organic renal damage, possibly leading to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome and papillary necrosis have been reported.
Expiration date
4 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
15 mg tablets: 4 tablets in a blister. 1 blister in a cardboard box.
10 tablets in a blister. 1 or 3 blisters in a cardboard box.
7.5 mg tablets: 10 tablets in a blister. 1 or 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
NOBEL ILACH SANAI VE TJARET A.Sh.
Location of the manufacturer and its business address
Sancaklar Koyu 81100 m. Duzce, Turkey.
