Movalis tablets 15mg, 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.

1 tablet contains:
Active ingredient: meloxicam - 15.0 mg
Excipients: sodium citrate dihydrate -30 mg, lactose monohydrate -20 mg, microcrystalline cellulose - 87.3 mg, povidone K25 - 9 mg, colloidal silicon dioxide - 3 mg, crospovidone - 4 mg, magnesium stearate - 1.7 mg.

- Hypersensitivity to the active ingredient or auxiliary components of the drug. There is a possibility of cross-sensitivity to acetylsalicylic acid and other NSAIDs;
- Symptoms of bronchial asthma, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs in history;
- Peptic ulcer / perforation of the stomach and duodenum in the acute stage or recently transferred;
- Crohn's disease or ulcerative colitis in the acute stage;
- Severe liver failure;
- Severe renal failure (if hemodialysis is not performed);
- Acute gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of diseases of the blood coagulation system;
- Severe uncontrolled heart failure;
- Children under 12 years of age, except for use in juvenile rheumatoid arthritis (if this indication is registered);
- Pregnancy;
- Breast-feeding;
- Therapy of perioperative pain during coronary artery bypass grafting (CABG);
With care:
- history of gastrointestinal tract diseases;
- congestive heart failure;
- renal failure;
- coronary heart disease;
- cerebrovascular diseases;
- dyslipidemia / hyperlipidemia;
- diabetes;
- peripheral arterial disease;
- elderly age;
- long-term use of NSAIDs;
- smoking;
- frequent alcohol consumption.

Pharmacological properties:
Pharmacodynamics
Movalis is a non-steroidal anti-inflammatory drug, belongs 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.
In vivo, meloxicam 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 cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that inhibition of COX-2 provides a therapeutic effect 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 ex vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when using human whole blood in vitro as a test system. Ex vivo, it was found that meloxicam (at doses of 7.5 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, which is involved in the process blood clotting (a reaction controlled by COX-1). These effects were dose dependent. It was shown ex vivo that meloxicam at the recommended doses did not affect platelet aggregation and bleeding time, in contrast to indomethacin. diclofenac. ibuprofen and naproxen.which significantly suppressed platelet aggregation and increased bleeding time.
In clinical studies, gastrointestinal (GI) side effects generally occurred less frequently with meloxicam 7.5 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.
Pharmacokinetics:
Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by the high absolute oral bioavailability (89%).
With a single dose of the drug in the form of tablets, the average maximum plasma concentration is reached within 5-6 hours. With repeated use, a steady state of pharmacokinetics is achieved within 3 to 5 days.
The range of differences between the maximum (Cmax) and basal concentrations (Cmin) of the drug during the steady state of pharmacokinetics after taking it once a day is relatively small and amounts to 0.4-1.0 ?g / ml - for a dose of 7.5 mg, and 0.8 -2.0 ?g / ml - for a dose of 15 mg. The maximum plasma concentration during the period of steady state pharmacokinetics is achieved within 5-6 hours when taking the tablets.
Concentrations of the drug after continuous use of the drug for more than 6 months are similar to those observed after 2 weeks of oral administration of 15 mg per day. When taken for more than 6 months, such a difference is unlikely.
Simultaneous food intake does not affect the absorption of the drug.
Distribution
Meloxicam binds well to plasma proteins (with albumin - 99%). Meloxicam penetrates into synovial fluid: local concentrations are approximately 50% of plasma concentrations.
The volume of distribution is low, an average of 11 liters. Individual fluctuations - 30-40%.
Metabolism
Meloxicam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives determined in the urine. 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 CYP 2C9 plays an important role in this metabolic transformation, and the CYP 3A4 isoenzyme is of additional importance. Peroxidase is involved in the formation of two other metabolites (constituting, respectively, 16% and 4% of the drug dose). the activity of which is likely to vary individually.
It is excreted equally with feces and urine, 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 elimination half-life of meloxicam is 20 hours.
Plasma clearance averages 8 ml / min. Meloxicam demonstrates linear pharmacokinetics at doses of 7.5 - 15 mg when taken orally.
Lack of liver and / or kidney function
Lack of liver function, as well as mild or moderate renal failure, does not significantly affect the pharmacokinetics of meloxicam.
In end-stage renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, therefore, in these patients, the daily dose should not exceed 7.5 mg.
Elderly patients
In elderly patients, the mean plasma clearance during steady state pharmacokinetics is slightly lower than in younger patients.
During the study of meloxicam in children, the pharmacokinetics of the drug was studied at doses used at the rate of 0.25 mg / kg. When comparing the indicators in children of different ages (2-6 years old, n = 7 and 7-14 years old, n = 11), a tendency towards a lower maximum plasma concentration (Cmax, -34%) and AUC0-? (-28%) in young children, and the clearance of the drug (adjusted for body weight) was higher in this group of children. Plasma concentrations of meloxicam in older children and adults are similar. In children of both age groups, the plasma half-lives of meloxicam were similar (13 hours) and slightly shorter than in adults (15-20 hours).

Side effects:
Below are described side effects, the connection of which with the use of the drug MovalisЃ, was regarded as possible.
Side effects, the connection of which with the intake of the drug was regarded as possible, and which were registered with the widespread use of the drug, are marked with a *.
From the side of hematopoietic organs:
Changes in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia, anemia.
From the immune system:
anaphylactoid / anaphylactic reactions, other immediate hypersensitivity reactions.
From the side of the central nervous system:
headache, dizziness, tinnitus, drowsiness, confusion, disorientation, mood changes *.
From the gastrointestinal tract:
perforation of the gastrointestinal tract, latent or overt gastrointestinal bleeding, possibly fatal, gastroduodenal ulcers, colitis, gastritis, esophagitis, stomatitis, abdominal pain, dyspepsia, diarrhea, nausea, vomiting, constipation , bloating, belching, transient changes in liver function indicators (for example, increased activity of transaminases or bilirubin), hepatitis.
On the part of the skin and skin appendages:
toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, bullous dermatitis, erythema multiforme *, pruritus, skin rash, urticaria, photosensitivity.
From the respiratory system:
bronchial asthma.
On the part of the cardiovascular system:
Increased blood pressure, palpitations, a feeling of blood rush to the face.
From the genitourinary system:
acute renal failure, changes in renal function indicators (increased serum creatinine and / or urea levels), urination disorders, including acute urinary retention, interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome *.
From the side of the organs of vision:
conjunctivitis, visual impairment, including blurred vision.
Common diseases:
Edema.

Overdose: The
antidote is not known, in case of an overdose of the drug, it is necessary to carry out: evacuation of the contents of the stomach and general supportive therapy. Cholestyramine accelerates the elimination of meloxicam.

Interaction with other medicinal products:
- Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates -
simultaneous administration with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergistic action) and is therefore not recommended. Concomitant use with other NSAIDs is not recommended.
- Selective serotonin reuptake inhibitors - increased risk of gastrointestinal bleeding.
- Sodium polystyrene sulfonate - due to the presence of sorbitol in MovalisЃ, joint administration may cause a risk of developing colon necrosis, with a possible fatal outcome.
- Anticoagulants for oral administration, antiplatelet drugs, heparin for systemic use, thrombolytic agents, serotonin reuptake inhibitors - simultaneous administration with meloxicam increases the risk of bleeding due to inhibition of platelet function.
- Lithium preparations - NSAIDs increase the plasma level of lithium by decreasing its excretion by the kidneys. It is recommended to monitor the lithium level during the appointment of MovalisЃ when changing the dose of lithium preparations and their cancellation.
- Methotrexate - NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration and hematological toxicity, while the pharmacokinetics of methotrexate does not change. In this regard, the simultaneous administration of Movalis and methotrexate at a dosage of more than 15 mg / week is not recommended.
The risk of developing an interaction between NSAIDs and methotrexate may also occur in patients using low-dose methotrexate, especially in patients with impaired renal function. Therefore, it is necessary to constantly monitor the number of blood cells and kidney function.
With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases.
- Contraception - NSAIDs reduce the effectiveness of intrauterine contraceptive devices.
- Diuretics - The use of NSAIDs in the case of dehydration of patients is accompanied by the risk of developing acute renal failure.
- Antihypertensive drugs (beta-blockers, angiotensin converting enzyme inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensive drugs due to the inhibition of prostaglandins, which have vasodilating properties.
- Antagonists of angiotensin-II receptors, when administered 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.
When used in conjunction with meloxicam drugs that have a known ability to inhibit CYP 2C9 and / or CYP ZA4 (or are metabolized with the participation of these enzymes), the possibility of pharmacokinetic interaction should be taken into account.
The possibility of interaction with oral antidiabetic drugs cannot be ruled out. With the simultaneous use of antacids, cimetidine, digoxin and furosemide, no significant pharmacokinetic interactions were identified.

Special instructions:
Patients suffering from diseases of the gastrointestinal tract 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 at any time during treatment, with or without a history of warning symptoms or a history of serious gastrointestinal complications. The consequences of these complications are generally more serious in the elderly.
Particular 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 such reactions were observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment. In such cases, the question of discontinuing the use of MovalisЃ should be considered.
Like other NSAIDs, MovalisЃ can increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, angina pectoris, 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 blood volume 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, cirrhosis of the liver, nephrotic syndrome or acute renal dysfunction, patients taking diuretics at the same time, as well as patients who have undergone major surgical interventions who 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, potassium and water retention, as well as to a decrease in 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, and adequate hydration should also be maintained.
Before starting treatment, a study of renal function is necessary.
In the case of combination therapy, renal function should also be monitored.
When using MovalisЃ (as well as most other NSAIDs), an episodic increase in the level of transaminases in the blood serum or other indicators of liver function is possible. 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, and therefore, such patients should be carefully monitored.
Like other NSAIDs, MovalisЃ can mask the symptoms of an underlying infectious disease.
As a drug that inhibits the synthesis of cyclooxygenase / prostaglandin, MovalisЃ may affect fertility and is therefore not recommended for women planning a pregnancy. In this regard, in women undergoing examination for such problems, it is recommended to cancel the use of MovalisЃ.
The maximum recommended daily dose of 7.5 and 15 mg tablets contains 47 and 20 mg of lactose, respectively. Patients with rare hereditary galactose intolerance, Lapp-lactase deficiency or impaired glucose / galactose adsorption should not take this drug.
In the case of the simultaneous use of anticoagulants for oral administration, ticlopidine, heparin for systemic use, thrombolytic agents, careful monitoring of the effect of anticoagulants is necessary.
Influence on the ability to drive vehicles and mechanisms:
Special studies regarding the effect of the drug on the ability to drive vehicles and mechanisms have not been conducted. However, patients with visual impairments, patients with drowsiness or other disorders of the central nervous system should refrain from this activity.