Movalis tablets 7.5mg, No. 20

• Symptomatic treatment:

• osteoarthritis (arthrosis, degenerative joint diseases), incl. with a pain component;

• rheumatoid arthritis;

• ankylosing spondylitis;

• other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathies, dorsopathies (for example, sciatica, low back pain, shoulder periarthritis), accompanied by pain.

Osteoarthritis with pain syndrome: 7.5 mg / day. If necessary, the dose can be increased to 15 mg / day.

Rheumatoid arthritis: 15 mg / day. Depending on the therapeutic effect, the dose can be reduced to 7.5 mg / day.

Ankylosing spondylitis: 15 mg / day. Depending on the therapeutic effect, the dose can be reduced to 7.5 mg / day.

In patients with an increased risk of adverse reactions (history of gastrointestinal tract disease, presence of risk factors for cardiovascular diseases), it is recommended to start treatment with a dose of 7.5 mg / day.

In patients with severe renal failure on hemodialysis, the dose should not exceed 7.5 mg / day.

General recommendations

Since the potential risk of adverse reactions depends on the dose and duration of treatment, the lowest possible dose and duration of use should be used. The maximum recommended daily dose is 15 mg.

Combined use

The drug should not be used concomitantly with other NSAIDs. The total dose of MovalisЃ, used in different dosage forms, should not exceed 15 mg / day.

Teenagers

The maximum dose in adolescents aged 12-18 years is 0.25 mg / kg and should not exceed 15 mg.

The use of tablets

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. The total daily dose should be taken at one time, with meals, with water or other liquid.

Tablets from pale yellow to yellow, round, one side convex with a beveled edge, on the convex side - the company logo, on the other side - the code and the concave risk; roughness of tablets is allowed.

1 tab.

meloxicam 7.5 mg

Excipients: sodium citrate dihydrate - 15 mg, lactose monohydrate - 23.5 mg, microcrystalline cellulose - 102 mg, povidone K25 - 10.5 mg, colloidal silicon dioxide - 3.5 mg, crospovidone - 16.3 mg, magnesium stearate - 1.7 mg.

• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs (including in history) due to the existing likelihood of cross-sensitivity;

• erosive and ulcerative lesions of the stomach and duodenum in the acute stage or recently transferred;

• inflammatory bowel disease (Crohn's disease or acute ulcerative colitis);

• severe liver failure;

• severe renal failure (if hemodialysis is not performed, CC <30 ml / min, as well as with confirmed hyperkalemia);

• progressive kidney disease; active gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of diseases of the blood coagulation system;

• severe uncontrolled heart failure;

• therapy of perioperative pain during coronary artery bypass grafting;

• pregnancy;

• lactation period (breastfeeding);

• children under 12 years of age;

• rare hereditary galactose intolerance (the maximum daily dose of the drug with a dosage of 7.5 mg and 15 mg meloxicam contains 47 mg and 20 mg of lactose, respectively);

• hypersensitivity to the active substance or auxiliary components of the drug.

• With care: a history of gastrointestinal diseases (gastric ulcer and duodenal ulcer, liver disease); congestive heart failure; renal failure (CC 30-60 ml / min); Ischemic heart disease; cerebrovascular diseases; dyslipidemia / hyperlipidemia; diabetes; concomitant therapy with the following drugs: oral corticosteroids, anticoagulants (including warfarin), antiplatelet agents, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); peripheral arterial disease; elderly age; long-term use of NSAIDs; smoking; frequent alcohol consumption.

pharmachologic effect

Non-steroidal anti-inflammatory drug (NSAID), refers to the derivatives of enolic acid and has anti-inflammatory, analgesic and antipyretic effects. The pronounced anti-inflammatory effect of meloxicam has been established in all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins - known mediators of inflammation. 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 a more selective inhibition of COX-2 compared to COX-1. Inhibition of COX-2 is believed to mediate the therapeutic effects of NSAIDs, while inhibition of the persistent isoenzyme COX-1 may cause gastric and renal side effects.The selectivity of meloxicam in relation to COX-2 has been confirmed in various test systems, both in vitro and in vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when using human whole blood in vitro as a test system. It was found that meloxicam (at doses of 7.5 mg and 15 mg) inhibited COX-2 more actively, exerting a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (a reaction controlled by COX-2) than on the production of thromboxane involved in blood coagulation ( reaction controlled by COX-1). These effects were dose dependent. Ex vivo studies have shown that meloxicam (at doses of 7.5 mg and 15 mg) has no effect on platelet aggregation and bleeding time.In clinical studies, gastrointestinal side effects in general occurred less frequently with meloxicam 7.5 mg and 15 mg than with other NSAIDs with which the comparison was made. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact that when taking meloxicam, such phenomena as dyspepsia, vomiting, nausea, and abdominal pain were less often observed. The incidence of upper gastrointestinal perforations, ulcers, and bleeding associated with meloxicam was low and dose-dependent.ulcers and bleeding associated with meloxicam were low and dose-dependent.ulcers and bleeding associated with meloxicam were low and dose-dependent.

Pharmacokinetics

Suction

Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by the high absolute bioavailability (90%) after oral administration. After a single use of meloxicam, Cmax in plasma is achieved within 5-6 hours. Simultaneous intake of food and inorganic antacids does not change absorption. When using the drug inside (in doses of 7.5 and 15 mg), its concentrations are proportional to the doses. The steady state of pharmacokinetics is achieved within 3-5 days. The range of differences between Cmax and Cmin of the drug after taking it 1 time / day is relatively small and amounts to 0.4-1.0 ?g / ml when using a dose of 7.5 mg, and when using a dose of 15 mg - 0.8-2.0 ?g / ml (the values ??of Cmin and Cmax during steady state pharmacokinetics), although values ??outside the specified range were also noted.Cmax in plasma during the period of steady state pharmacokinetics is achieved 5-6 hours after oral administration.

Distribution

Meloxicam binds very well to plasma proteins, mainly albumin (99%). Penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the plasma concentration. 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 an intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that the isoenzyme CYP2C9 plays an important role in this metabolic transformation, and the isoenzyme CYP3A4 plays an additional role. The formation of the other two metabolites (making up 16% and 4% of the drug dose, respectively) involves peroxidase, the activity of which is likely to vary individually.

Withdrawal

It is excreted equally through the intestines and by the kidneys, mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged with feces, in urine unchanged the drug is found only in trace amounts. The average T1 / 2 of 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

Lack of liver function, as well as mild renal failure, has no significant effect on the pharmacokinetics of meloxicam. The rate of elimination of meloxicam from the body is significantly higher in patients with moderate renal failure. Meloxicam binds to plasma proteins worse in patients with end-stage renal failure. In end-stage renal failure, an increase in Vd can lead to higher concentrations of free meloxicam, therefore, in these patients, the daily dose should not exceed 7.5 mg.

Elderly patients

Elderly patients in comparison with young patients have similar pharmacokinetic parameters. In elderly patients, the mean plasma clearance during steady state pharmacokinetics is slightly lower than in younger patients. Older women have higher AUC values ??and a longer T1 / 2 compared to younger patients of both sexes.

Side effect

From the hematopoietic system: infrequently - anemia; rarely - a change in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia.

Immune system disorders: infrequently - other immediate-type hypersensitivity reactions *; frequency not established - anaphylactic shock *, anaphylactoid reactions *.

From the nervous system: often - headache; infrequently - dizziness, drowsiness. Mental disorders: often - mood changes *; frequency not established - confusion *, disorientation *.

From the senses: infrequently - vertigo; rarely - conjunctivitis *, visual impairments, including blurred vision *, tinnitus.

From the gastrointestinal tract: often - abdominal pain, dyspepsia, diarrhea, nausea, vomiting; infrequently - latent or overt gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, belching; rarely - gastroduodenal ulcers, colitis, esophagitis; very rarely - perforation of the gastrointestinal tract.

From the liver: infrequently - transient changes in liver function indicators (for example, an increase in transaminase activity or bilirubin concentration); very rarely - hepatitis *.

On the part of 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 allergy to acetylsalicylic acid or other NSAIDs.

From the side of the cardiovascular system: infrequently - increased blood pressure, a feeling of 'rush' of blood to the face; rarely - palpitations.

From the urinary system: infrequently - changes in renal function indicators (increased serum creatinine and / or urea levels), 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 inhibit bone marrow hematopoiesis (for example, methotrexate) can provoke cytopenia. Gastrointestinal bleeding, ulceration, or perforation can be fatal. As with other NSAIDs, the possibility of the appearance of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome is not excluded.

Application during pregnancy and lactation

The use of MovalisЃ is contraindicated in pregnancy. It is known that NSAIDs are excreted in breast milk, therefore, the use of MovalisЃ during breastfeeding is contraindicated. As a drug that inhibits the synthesis of COX / prostaglandin, MovalisЃ may affect fertility and is therefore not recommended for women planning a pregnancy. Meloxicam may delay ovulation. In this regard, in women who have problems with conception and undergoing examination for such problems, it is recommended to cancel the use of the drug MovalisЃ.

Application for violations of liver function

The drug is contraindicated in severe liver failure. No dose adjustment is required in patients with (compensated) cirrhosis of the liver.

Application for impaired renal function

The drug is contraindicated in severe renal failure (if hemodialysis is not performed, CC <30 ml / min, as well as with confirmed hyperkalemia), progressive kidney disease. The drug should be prescribed with caution in case of renal failure (CC 30-60 ml / min). In patients with severe renal failure on hemodialysis, the dose should not exceed 7.5 mg / day. In patients with mild to moderate renal insufficiency (CC> 25 ml / min), dose adjustment is not required.

Application in children

The use of the drug in children under 12 years of age is contraindicated. Use in elderly patients The drug should be prescribed with caution in elderly patients.

special instructions

Patients with gastrointestinal diseases should be monitored regularly. If ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, MovalisЃ must be canceled. Gastrointestinal ulcers, perforation, or bleeding can occur with NSAIDs at any time with or without a history of alarming symptoms or a history of serious gastrointestinal complications. The consequences of these complications are generally more serious in the elderly. When using the drug MovalisЃ, such serious skin reactions as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis can develop. Therefore, special attention should be paid to patients reporting the development of adverse events from 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 a skin rash, changes in mucous membranes or other signs of hypersensitivity appear, the question of discontinuing the use of MovalisЃ should be considered. There are cases when taking NSAIDs to increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, angina pectoris attack, possibly fatal. This risk increases with prolonged use of the drug, as well as in patients with a history of the above diseases and those predisposed to such diseases. NSAIDs inhibit the synthesis of prostaglandins in the kidney, 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 the withdrawal of NSAIDs, renal function is usually restored to its original level. The most at risk of developing this reaction are elderly patients, patients with dehydration, congestive heart failure, liver cirrhosis, nephrotic syndrome or acute renal dysfunction, patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists, and also patients who have undergone major surgical interventions that lead to hypovolemia. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. The use of NSAIDs in conjunction with diuretics can lead to sodium retention,potassium and water, as well as to reduce the natriuretic effect of diuretics. As a result, predisposed patients may experience increased signs of heart failure or hypertension. Therefore, careful monitoring of the condition of such 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 using the drug Movalis (as well as most other NSAIDs), an episodic increase in the activity of transaminases or other indicators of liver function in the blood serum was reported. In most cases, this increase was small and transient. If the identified changes are significant or do not decrease over time,MovalisЃ should be canceled and the identified laboratory changes should be monitored. Weakened or emaciated patients may be less tolerant of adverse events, therefore such patients require careful monitoring. Like other NSAIDs, MovalisЃ can mask the symptoms of an infectious disease. As a drug that inhibits the synthesis of COX / prostaglandin, MovalisЃ can affect fertility and is therefore not recommended for women who have difficulty conceiving. In women undergoing examination for this reason, it is recommended to cancel the use of the drug MovalisЃ. In patients with mild to moderate renal insufficiency (CC> 25 ml / min), dose adjustment is not required. No dose adjustment is required in patients with (compensated) cirrhosis of the liver.Influence on the ability to drive vehicles and control mechanisms Special clinical studies of the effect of the drug on the ability to drive a car and mechanisms have not been conducted. However, when driving and working with mechanisms, the possibility of dizziness, drowsiness, visual impairment or other disorders of the central nervous system should be taken into account. Patients should be careful when driving and operating machinery.Patients should be careful when driving and operating machinery.Patients should be careful when driving and operating machinery.

Overdose

Insufficient data have been accumulated on cases associated with drug overdose. Symptoms typical of an NSAID overdose are likely to be present 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 unknown, in case of an overdose of the drug, evacuation of the stomach contents and general supportive therapy should be performed. Cholestyramine accelerates the elimination of meloxicam.

Drug interactions

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concomitant use with meloxicam increases the risk of gastrointestinal ulcers and gastrointestinal bleeding (due to synergistic action). Concomitant use with other NSAIDs is not recommended. Anticoagulants for oral administration, heparin for systemic use, thrombolytic agents - simultaneous administration with meloxicam increases the risk of bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary. Antiplatelet drugs, serotonin reuptake inhibitors - simultaneous administration with meloxicam increases 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.Lithium preparations - NSAIDs increase the plasma level of lithium by decreasing its excretion by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. If necessary, simultaneous use is recommended to carefully monitor the concentration of lithium in the plasma during the entire course of the use of lithium preparations. Methotrexate - NSAIDs reduce the secretion of methotrexate by the kidneys, 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 counts 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. Contraception - There is evidence that NSAIDs can reduce the effectiveness of intrauterine contraceptive devices, but this has not been proven. Diuretics - the use of NSAIDs while taking diuretics in case of dehydration of patients is accompanied by the risk of developing acute renal failure. Antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensive drugs by inhibiting prostaglandins, which have vasodilating properties. Angiotensin II receptor antagonists, as well as ACE inhibitors, when used together with NSAIDs, increase the decrease in glomerular filtration, which, thereby, can lead to the development of acute renal failure,especially in patients with impaired renal function. Cholestyramine, binding meloxicam in the gastrointestinal tract, leads to its faster excretion. NSAIDs, acting on renal prostaglandins, can increase the nephrotoxicity of cyclosporine. Pemetrexed - with the simultaneous use of meloxicam and pemetrexed in patients with CC from 45 to 79 ml / min, meloxicam should be discontinued 5 days before starting pemetrexed and may be resumed 2 days after the end of the drug. If there is a need for the combined use of meloxicam and pemetrexed, then patients should be closely monitored, especially with regard to myelosuppression and the occurrence of side effects from the gastrointestinal tract. In patients with CC <45 ml / min, the use of meloxicam in conjunction with pemetrexed is not recommended.With the simultaneous use of drugs with meloxicam that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or are 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 hypoglycemic agents for oral administration (for example, sulfonylurea derivatives, nateglinide), an interaction mediated by CYP2C9 is possible, which can lead to an increase in the concentration of both hypoglycemic agents and meloxicam in the blood. Patients who are simultaneously taking meloxicam with sulfonylureas or nateglinide should carefully monitor the blood glucose concentration due to the possibility of hypoglycemia.With the simultaneous use of meloxicam with antacids, cimetidine, digoxin and furosemide, no significant pharmacokinetic interaction was revealed.