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Active ingredients
Meloxicam
Release form
Pills
Composition
1 tablet contains the Active substance: meloxicam - 15.0 mg Auxiliary substances: sodium citrate dihydrate - 15 mg (30 mg), lactose monohydrate - 23.5 mg (20 mg), microcrystalline cellulose - 102 mg (87.3 mg), povidone K25 - 10.5 mg (9 mg), colloidal silicon dioxide - 3.5 mg (3 mg), crospovidone - 16.3 mg (14 mg), magnesium stearate - 1.7 mg.
Pharmacological effect
Non-steroidal anti-inflammatory drug (NSAIDs), is a derivative of enolic acid and has anti-inflammatory, analgesic and antipyretic effects. A pronounced anti-inflammatory effect of meloxicam is established on all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins - known inflammatory mediators. Meloxicam in vivo inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the gastric mucosa or kidneys. These differences are associated with more selective inhibition of COX-2 compared with COX-1. Inhibition of COX-2 is believed to provide the therapeutic effect of NSAIDs, whereas inhibition of a constantly present COX-1 isoenzyme may be the cause of side effects from the stomach and kidneys. The selectivity of meloxicam with respect to COX-2 was confirmed in various test systems, both in vitro and in vivo. The selective ability of meloxicam to inhibit COX-2 is shown when using in vitro human whole blood as a test system. It was found that meloxicam (at doses of 15 mg) more actively inhibited COX-2, having a greater inhibitory effect on the production of prostaglandin E2, stimulated by lipopolysaccharide (reaction controlled by COX-2) than on the production of thromboxane involved in blood clotting (a reaction controlled COX-1). These effects depended on the magnitude of the dose. Ex vivo studies have shown that meloxicam (in doses of 15 mg) had no effect on platelet aggregation and bleeding time. In clinical studies, side effects from the gastrointestinal tract as a whole occurred less frequently when taking meloxicam 15 mg than when taking other NSAIDs, which were compared. This difference in the frequency of side effects from the gastrointestinal tract, mainly due to the fact that while taking meloxicam, such phenomena as dyspepsia, vomiting, nausea, abdominal pain were less common.The frequency of perforations in the upper GI tract, ulcers and bleeding, which were associated with the use of meloxicam, was low and depended on the dose of the drug.
Pharmacokinetics
Absorption Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by the high absolute bioavailability (90%) after oral administration. After a single application of meloxicam Cmax in plasma is achieved within 5-6 hours. Simultaneous ingestion of food and inorganic antacids does not alter absorption. When using the drug inside (in doses of 7.5 and 15 mg), its concentration is proportional to the dose. The steady state pharmacokinetics is achieved within 3-5 days. The range of differences between max and min of the drug after its administration 1 time / day is relatively small and amounts to 0.4-1.0 mcg / ml when using a dose of 7.5 mg, and when using a dose of 15 mg - 0.8-2.0 mcg / ml (respectively, min values are given and max in the period of steady state pharmacokinetics), although values outside the specified range were also noted. max in plasma in the period of steady state pharmacokinetics is achieved within 5-6 hours after ingestion. Distribution Meloxicam is very well bound to plasma proteins, especially albumin (99%). Penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% concentration in plasma. Vd after repeated oral administration of meloxicam (in doses from 7.5 mg to 15 mg) is about 16 liters, with a coefficient of variation from 11 to 32%. Metabolism Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the dose), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that the CYP2C9 isoenzyme plays an important role in this metabolic transformation, CYP3A4 isoenzyme plays an additional role. Peroxidase is involved in the formation of two other metabolites (constituting 16% and 4%, respectively, of the dose), the activity of which is likely to vary individually. Withdrawal Equally excreted through the intestines and the kidneys, mainly in the form of metabolites. In an unchanged form with feces less than 5% of the daily dose is excreted, in the urine the drug is found in unchanged form only in trace amounts. The average T1 / 2 meloxicam varies from 13 to 25 hours.Plasma clearance averages 7-12 ml / min after a single dose of meloxicam. Pharmacokinetics in special clinical situations The insufficiency of the liver, as well as poorly expressed renal insufficiency, does not have a significant effect on the pharmacokinetics of meloxicam. The rate of elimination of meloxicam from the body is significantly higher in patients with moderately severe renal insufficiency. Meloxicam binds worse to plasma proteins in patients with end-stage renal disease. In terminal renal failure, an increase in Vd can lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg. Elderly patients compared with young patients have similar pharmacokinetic indicators. In elderly patients, the mean plasma clearance during the period of equilibrium pharmacokinetics is slightly lower than in younger patients. Older women have higher AUC values and a longer T1 / 2, compared with younger patients of both sexes.
Indications
Symptomatic treatment: - osteoarthritis (arthrosis, degenerative diseases of the joints), including with a pain component; - rheumatoid arthritis; - ankylosing spondylitis; - other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathy, dorsopathy (for example, sciatica, lower back pain, shoulder periarthritis), accompanied by pain.
Contraindications
- A complete or incomplete combination of asthma, recurrent nasal polyposis and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs (including history) due to the likelihood of cross-sensitivity; - erosive-ulcerative lesions of the urine; and duodenal ulcer in the stage of exacerbation or recently transferred; - inflammatory bowel disease (Crohn's disease or ulcerative colitis in the stage of exacerbation); - liver failure is severe oh degree; - severe renal failure (if hemodialysis is not performed, CC <30 ml / min, and also with confirmed hyperkalemia); - progressive kidney disease; - active gastrointestinal bleeding,recent cerebrovascular hemorrhage or an established diagnosis of coagulation disorders; severe uncontrolled heart failure; therapy of perioperative pain during coronary artery bypass surgery; pregnancy; lactation (breastfeeding); children up to 12 years of age; rare hereditary intolerance galactose (the maximum daily dose of the drug with a dosage of meloxicam 7.5 mg and 15 mg contains 47 mg and 20 mg of lactose, respectively); viscosity to the active substance or auxiliary components of the drug.
Precautionary measures
- history of gastrointestinal tract diseases (gastric ulcer and duodenal ulcer, liver disease); - congestive heart failure; - renal failure (CC 30-60 ml / min); - IHD; - cerebrovascular diseases; - dyslipidemia / hyperlipidemia; - diabetes - concomitant therapy with the following drugs: oral GCS, anticoagulants (including warfarin), antiplatelet agents, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertralin); - peripheral artery disease; - lived age - long-term use of NSAIDs - smoking - a frequent alcohol consumption.
Use during pregnancy and lactation
The use of the drug Movalis is contraindicated in pregnancy. It is known that NSAIDs penetrate into breast milk, so the use of Movalis during breastfeeding is contraindicated. As a drug inhibiting the synthesis of cyclooxygenase / prostaglandin, Movalis may affect fertility, and therefore is not recommended for women planning a pregnancy. Meloxicam can lead to delayed ovulation. In this regard, for women who have problems with conception and are being examined for similar problems, it is recommended that Movalis be discontinued.
Dosage and administration
The drug is taken orally 1 time / day, with food, with water or other liquid. In osteoarthritis with pain, the daily dose is 7.5 mg, if necessary, the dose can be increased to 15 mg / day. In rheumatoid arthritis, the drug is prescribed in a dose of 15 mg / day,depending on the therapeutic effect, the dose may be reduced to 7.5 mg / day. In ankylosing spondylitis, the drug is prescribed at a dose of 15 mg / day, depending on the therapeutic effect, the dose may be reduced to 7.5 mg / day. The maximum recommended daily dose is 15 mg. In patients with an increased risk of adverse reactions (a history of gastrointestinal diseases, the presence of risk factors for cardiovascular diseases), it is recommended to begin treatment with a dose of 7.5 mg / day. The potential risk of adverse reactions depends on the dose and duration of treatment, the minimum effective dose should be prescribed for the shortest possible course. In patients with severe renal failure on hemodialysis, the dose of Movalis should not exceed 7.5 mg / day. The maximum dose in adolescents aged 12 -18 years old is 0.25 mg / kg and should not exceed 15 mg. The use of the drug is contraindicated in children under 12 years of age, due to the impossibility of selecting the appropriate dose for this age group. combined. Do not use the drug simultaneously with other NSAIDs. The total dose of Movalis used in different dosage forms should not exceed 15 mg / day.
Side effects
The following side effects are described, the connection of which with the use of Movalis was regarded as possible. The side effects registered during postmarketing use, the connection of which with the administration of the drug was regarded as possible, are marked with a * sign. The following categories are used within the systemic organ classes : very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000); not established. On the part of the blood and lymphatic system: infrequently - anemia; rarely - change in the number of blood cells, including changes in leukocyte formula, leukopenia, thrombocytopenia. From the immune system: rarely - other immediate-type hypersensitivity reactions *; frequency not established - anaphylactic shock *, anaphylactoid reactions *. On the nervous system: often - headache; infrequently - dizziness, drowsiness. Psychiatric disorders: often - changes in mood *; frequency not set - confusion *,disorientation *. For the senses: infrequently - vertigo; rarely - conjunctivitis *, visual disturbances, including blurred vision *, tinnitus. From the gastrointestinal tract: often - abdominal pain, dyspepsia, diarrhea, nausea, vomiting; infrequently - latent or overt gastrointestinal bleeding, gastritis *, stomatitis, constipation, abdominal distention, belching; rarely - gastroduodenal ulcers, colitis, esophagitis; very rarely - gastrointestinal perforation. From the side of the liver: infrequently - transient changes in liver function indicators (for example, increased transaminase activity or bilirubin concentration); very rarely - hepatitis *. On the skin and subcutaneous tissues: infrequently - angioedema, itching, skin rash; rarely, toxic epidermal necrolysis *, Stevens-Johnson syndrome *, urticaria; very rarely - bullous dermatitis *, erythema multiforme *; frequency not established - photosensitivity. From the respiratory system: rarely - bronchial asthma in patients with allergies to acetylsalicylic acid or other NSAIDs. From the side of the cardiovascular system: infrequently - increased blood pressure, feeling flushed; rarely - palpitations. From the urinary system: infrequently - changes in kidney function indicators (increased serum creatinine and / or urea), urinary disorders, including acute urinary retention *; very rarely - acute renal failure *. From the genitals and mammary gland: infrequently - late ovulation *; frequency not established - infertility in women *. Combined use with drugs that suppress bone marrow hematopoiesis (for example, methotrexate) can provoke cytopenia. Gastrointestinal bleeding, an ulcer or perforation can be fatal. interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome.
Overdose
Data on cases associated with overdose of the drug has been accumulated insufficiently. There will probably be symptoms characteristic of an NSAID overdose, in severe cases: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole. Treatment: the antidote is not known, in case of an overdose of the drug should be evacuated stomach contents and general supportive therapy. Kolestiramin accelerates the elimination of meloxicam.
Interaction with other drugs
With the simultaneous use of other prostaglandin synthesis inhibitors with meloxicam, including GCS and salicylates, increases the risk of gastrointestinal ulcers and gastrointestinal bleeding (due to synergism of action). The simultaneous use of meloxicam and other NSAIDs is not recommended. Anti-coagulants for oral administration, heparin for systemic use, thrombolytic agents, while used with meloxicam, increase the risk of bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary. Antiplatelet drugs, serotonin reuptake inhibitors, while used with meloxicam, increase the risk of bleeding due to inhibition of platelet function. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary. NVPs increase the concentration of lithium in the plasma by reducing its excretion by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. If necessary, the simultaneous use of recommended careful monitoring of the concentration of lithium in the plasma during the entire course of the use of drugs lithium. NVPP reduce tubular secretion of methotrexate, thereby increasing its concentration in plasma. The simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. In the case of simultaneous use, careful monitoring of renal function and blood formula is necessary. Meloxicam may increase the hematological toxicity of methotrexate, especially in patients with impaired renal function. With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases. There is evidence that NSAIDs can reduce the effectiveness of intrauterine contraceptive devices, but this has not been proven. NSAIDs reduce the effect of antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics) due to inhibition of prostaglandins,possessing vasodilating properties. The combined use of NSAIDs and angiotensin II receptor antagonists, as well as ACE inhibitors, enhances the effect of reducing glomerular filtration, thereby leading to the development of acute renal failure, especially in patients with impaired kidney function. leads to its more rapid removal. NVPP, having an effect on renal prostaglandins, can enhance the nephrotoxicity of cyclosporine. In patients with CC from 45 to 79 ml / min, the use of meloxic and should be discontinued 5 days before you start taking pemetrexed, and possibly to resume within 2 days after receiving pemetrexed. If there is a need to use meloxicam and pemetrexed together, then patients should be carefully monitored, especially with regard to myelosuppression and the occurrence of gastrointestinal side effects. In patients with QA <45 ml / min, the use of meloxicam together with pemetrexed is not recommended. When used with meloxicam, drugs that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or metabolized with the participation of these enzymes), such as sulfonylurea derivatives or probenecid , the possibility of pharmacokinetic interaction should be taken into account. When used together with antidiabetic agents for oral administration (for example, sulfonylurea derivatives, atteglinidom) possible interaction mediated by CYP2C9, which can lead to an increase in the concentration of both hypoglycemic agents and meloxicam in the blood. Patients concurrently taking meloxicam with sulfonylurea or nateglinide should carefully monitor the concentration of glucose in the blood due to the possibility of hypoglycemia. With the simultaneous use of antacids, cimetidine, digoxin and furosemide, there was no significant pharmacokinetic interaction.
special instructions
Patients with gastrointestinal diseases should be monitored regularly. If ulceration of the gastrointestinal tract or gastrointestinal bleeding occurs, Movalis should be canceled. Gastrointestinal ulcers, perforation or bleeding can occur during the use of NSAIDs at any time if there are warning signs or information about serious gastrointestinal complications in the history, and in the absence of signs.The consequences of these complications are generally more severe in the elderly. With the use of Movalis, serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis may develop. Therefore, special attention should be paid to patients reporting the development of adverse events on the skin and mucous membranes, as well as hypersensitivity reactions to the drug, especially if similar reactions have been observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment. If the first signs of skin rash, mucous membranes or other signs of hypersensitivity appear, discontinue use of Movalis should be considered. There have been described cases of increased risk of serious cardiovascular thrombosis, myocardial infarction, angina, possibly with a fatal outcome, when taking NSAIDs. This risk increases with long-term use of the drug, as well as in patients with the above mentioned diseases in history and predisposed to such diseases. NVP inhibit the synthesis of prostaglandins in the kidneys, which are involved in maintaining renal perfusion. The use of NSAIDs in patients with reduced renal blood flow or reduced BCC can lead to decompensation of latent renal failure. After abolishing NSAIDs, the kidney function is usually restored to its original level. Elderly patients, patients with dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal dysfunction, patients simultaneously receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, and also patients who have undergone serious surgery that leads to hypovolemia. In these patients, at the beginning of therapy, diuresis and kidney function should be carefully monitored. The use of NSAIDs in conjunction with diuretics can lead to sodium, potassium, and water retention, as well as to a decrease in the natriuretic effect of diuretics.As a result, in predisposed patients, signs of heart failure or arterial hypertension may increase. Therefore, careful monitoring of the condition of these patients is necessary, as well as the maintenance of adequate hydration. Before starting treatment, a study of renal function is necessary. In the case of combination therapy, renal function should also be monitored. When Movalis was used (as well as most other NSAIDs), an episodic increase in transaminase activity or other indicators of liver function in blood serum was reported. In most cases, this increase was small and transient. If the identified changes are significant or do not diminish over time, Movalis should be canceled and monitored laboratory changes should be observed. Weakened or depleted patients may be worse tolerated by adverse events, so such patients require careful observation. Like other NSAIDs, Movalis can mask the symptoms of an infectious disease. How COX / prostaglandin synthesis inhibiting drug Movalis may affect fertility and is therefore not recommended for women who have difficulty and with conception. In women undergoing examination for this reason, it is recommended that the Movavis medication be discontinued. Patients with mild to moderate renal insufficiency (CC> 25 ml / min) do not require dose adjustment. Patients with liver cirrhosis (compensated) do not need dose adjustment. on the ability to drive vehicles and control mechanismsSpecialty clinical studies of the effect of the drug on the ability to drive and mechanisms were not conducted. However, when driving and working with mechanisms, the possibility of developing dizziness, drowsiness, visual impairment or other disorders of the central nervous system should be taken into account. Patients should be careful when driving a car and controlling mechanisms.