Мовалис®

General characteristics. Structure:

Active ingredient: 7,5 mg or 15 mg of a meloksikam.

Excipients: citrate sodium dihydrate, lactoses monohydrate, cellulose microcrystallic, K25 povidone, silicon dioxide colloid, кросповидон, magnesium stearate.

The non-steroidal anti-inflammatory drug having the antiinflammatory, anesthetizing and febrifugal effect.

Pharmacological properties:

Pharmacodynamics. Movalis - non-steroidal anti-inflammatory drug, treats derivatives of enolovy acid. The expressed antiinflammatory action of a meloksikam is established on all standard models of an inflammation. The mechanism of action of a meloksikam consists in its ability to inhibit synthesis of prostaglandins - the known mediators of an inflammation.

In vivo to meloksika inhibits synthesis of prostaglandins in the place of an inflammation more than in a mucous membrane of a stomach or kidneys.

These distinctions are connected with more selection inhibition of cyclooxygenase-2 (TsOG-2) in comparison with cyclooxygenase-1 (TsOG-1). It is considered that the inhibition of TsOG-2 provides therapeutic effect of NPVP whereas the inhibition of constantly present isoenzyme of TsOG-1 can be the cause of side effects from a stomach and kidneys.

Selectivity of a meloksikam concerning TsOG-2 is confirmed in various test systems, both in vitro, and ex vivo. The selection ability of a meloksikam to inhibit TsOG-2 is shown when using as test system of whole blood of the person of in vitro. Ex vivo is established that to meloksika (in doses of 7,5 and 15 mg) TsOG-2 inhibited more actively, exerting the greater inhibiting influence on products of E2 prostaglandin stimulated lipopolisakharidy (the reaction controlled by TsOG-2), than on products of the thromboxane participating in blood coagulation process (the reaction controlled by TsOG-1). These effects depended on dose size. Ex vivo is shown that to meloksika in the recommended doses did not influence aggregation of thrombocytes and a bleeding time unlike indometacin. diclofenac. ibuprofen and Naproxenum. which considerably suppressed aggregation of thrombocytes and increased a bleeding time.

In clinical trials side effects from the digestive tract (DT) in general arose less often at reception of a meloksikam of 7,5 and 15 mg, than at reception of other NPVS with which comparison was carried out. This distinction in the frequency of side effects from a GIT is generally connected with the fact that at reception of a meloksikam such phenomena as dyspepsia, vomiting, nausea, abdominal pains were less often observed. Frequency of perforation in upper parts of a GIT, ulcers and bleedings which communicated using a meloksikam was low and depended on drug dose size.

Pharmacokinetics. Meloksikam is well soaked up from digestive tract what high absolute bioavailability at intake (89%) testifies to.

At a single dose of drug in the form of tablets average maximum concentration in plasma is reached within 5-6 hour. At repeated use the steady condition of pharmacokinetics is reached from 3 to 5 days in time.

Range of distinctions between maximum (Cmax) and basal concentration (Cmin) of drug in the period of a steady condition of pharmacokinetics after its reception is rather small once a day and makes 0,4-1,0 mkg/ml - for a dose of 7,5 mg, and 0.8-2.0 mkg/ml - for a dose of 15 mg. The maximum concentration in plasma in the period of a steady condition of pharmacokinetics is reached within 5-6 hour at reception of tablets.

Concentration of drug after constant administration of drug within more than 6 months, are similar to concentration which are noted after 2 weeks of oral administration 15 mg a day. At reception more than 6 months such distinctions are improbable.

The concomitant use of food does not influence drug absorption. Distribution. Meloksikam well contacts plasma proteins (with albumine - 99%). Meloksikam gets into synovial fluid: local concentration make about 50% of concentration in plasma. Distribution volume low, averages 11 l. Individual fluctuations - 30-40%.

Metabolism. Meloksikam is almost completely metabolized in a liver with formation of the 4th pharmacological inactive derivatives defined in urine. The main metabolite, to 5-karboksimeloksika (60% of dose size), is formed by oxidation of an intermediate metabolite, a 5-gidroksimetilmeloksikam who is also excreted, but to a lesser extent (9% of dose size). The researches in vitro showed that in this metabolic transformation an important role is played by CYP 2C9, additional value has CYP ZA4 isoenzyme. Peroxidase takes part in formation of two other metabolites (making, respectively, 16% and 4% of drug dose size). which activity probably individually varies.

It is removed equally with a stake and urine, it is preferential in the form of metabolites. In not changed view with a stake less than 5% of the size of a daily dose are removed, in urine in not changed look drug is found only in trace quantities. The average elimination half-life of a meloksikam makes 20 hours.

The plasma clearance averages 8 ml/min. Meloksikam shows linear pharmacokinetics in doses of 7,5 - 15 mg at intake.

Insufficiency of function of a liver and/or kidneys. Insufficiency of function of a liver, and also poorly or moderately expressed renal failure has no significant effect on pharmacokinetics of a meloksikam.

At a terminal renal failure increase in volume of distribution can result in higher concentration of a free meloksikam therefore at these patients the daily dose should not exceed 7,5 mg.

Elderly patients. At elderly patients the average plasma clearance in the period of a steady condition of pharmacokinetics is a little lower, than at young patients.

During the research of a meloksikam at children, the drug pharmacokinetics in the doses applied at the rate of 0,25 mg/kg was studied. When comparing indicators at children of different age (2-6 years, n = 7 and 7-14 years, n = 11) established a tendency to lower maximum concentration in plasma (Cmax,-34%) and AUC0-∞ (-28%) at children of younger age, and the clearance of drug (adjusted for body weight) at this group of children was higher. Concentration of a meloksikam in plasma at children of advanced age and adults are similar. Children of both age groups from plasma had similar elimination half-lives of a meloksikam (13 hours) and a little shorter, than at adults (15-20 hours).

Indications to use:

Symptomatic treatment:
- osteoarthritis (arthrosis, degenerative diseases of joints),
- pseudorheumatism,
- ankylosing spondylitis.

Route of administration and doses:

Osteoarthritis: 7,5 mg a day. If necessary this dose can be increased to 15 mg a day.

Pseudorheumatism: 15 mg a day. Depending on medical effect this dose can be lowered to 7,5 mg a day.

Ankylosing spondylitis: 15 mg a day. Depending on medical effect this dose can be lowered to 7,5 mg a day.

At patients with the increased risk of side reactions it is recommended to begin treatment with a dose of 7,5 mg a day.

At the patients with the expressed renal failure who are on a hemodialysis a dose should not exceed 7,5 mg a day.

At teenagers. The maximum dose at teenagers makes 0,25 mg/kg. As a rule, drug has to be used only at teenagers and adults (see the section on contraindications). The maximum recommended daily dose - 15 mg. Tablets should be washed down with water or other liquid and to accept during food.

As the risk of emergence of side reactions depends on the size of a dose and duration of use it is necessary to use drug during perhaps short term with perhaps low effective dose.

The combined use. The total daily dose of the drug Movalis® used in the form of tablets, candles, suspension for intake and injections should not exceed 15 mg.

Features of use:

The patients having digestive tract diseases have to be observed regularly. At emergence of a canker of digestive tract or gastrointestinal bleeding of Movalis® it is necessary to cancel.

Ulcers in digestive tract, perforation or bleeding can arise during treatment at any time, as in the presence of alarming symptoms or data on serious gastrointestinal complications in the anamnesis, and in the absence of these signs. Effects of these complications in general are more serious at elderly people.

Special attention should be paid to the patients reporting about development of the undesirable phenomena from skin and mucous membranes, and also hypersensitivity reactions to drug, especially, if similar reactions were observed during the previous courses of treatment. Development of similar reactions is observed, as a rule, within the first month of treatment. In such cases the question of phase-out of Movalisa® has to be considered.

As well as the risk of development of serious cardiac vascular thromboses, a myocardial infarction, a stenocardia attack can raise other NPVP, Movalis®, it is possible from the death. Such risk increases at prolonged use of drug, and also at patients with above the specified diseases in the anamnesis and predisposed to such diseases.

NPVP inhibit synthesis of prostaglandins which participate in maintenance of renal perfusion in kidneys. Use of NPVP for patients with a reduced renal blood-groove or the reduced volume of the circulating blood can lead to a decompensation is hidden the proceeding renal failure. After cancellation of NPVP function of kidneys is usually recovered to initial level. Most elderly patients, patients at whom dehydration, congestive heart failure, cirrhosis, a nephrotic syndrome or acute disorders of function of kidneys, patients, at the same time accepting diuretic means, and also the patients who transferred serious surgical interventions which conduct to a hypovolemia is noted are subject to risk of development of this reaction. At such patients at the beginning of therapy it is necessary to control a diuresis and function of kidneys carefully.

Use of NPVP together with diuretics can lead to a delay of sodium, potassium and water, and also to decrease in a natriuretic effect of diuretics. As a result of it at predisposed patients strengthening of symptoms of heart failure or hypertensia is possible. Therefore careful control of a condition of such patients is necessary, and also at them adequate hydration has to be supported.

Prior to treatment the research of function of kidneys is necessary. In case of carrying out a combination therapy it is necessary to control function of kidneys also.

When using Movalisa® (as well as majority of other NPVP) perhaps incidental increase in level of transaminases in blood serum or other indicators of function of a liver. In most cases this increase was small and passing.

If the revealed changes are essential or do not decrease over time, Movalis® should be cancelled and to make observation of the revealed laboratory changes.

The weakened or exhausted patients can worse transfer the undesirable phenomena in this connection, such patients have to be observed carefully.

Like other NPVP Movalis® can mask symptoms of the basic infectious disease.
As the drug inhibiting synthesis of cyclooxygenase/prostaglandin Movalis® can exert impact on fertility and therefore it is not recommended to the women planning pregnancy. In this regard at the women undergoing inspection concerning similar to problems cancellation of reception of Movalisa® is recommended.

The maximum recommended daily dose of tablets 7,5 and 15 of mg contains 47 and 20 mg of lactose respectively. Patients with rare hereditary intolerance to a galactose, with Lapp-laktazny deficit or disturbance of adsorption of a glucose/galactose, should not accept this drug.

In case of simultaneous use of anticoagulants intake, a tiklopidina, heparin for system use, thrombolytic means requires careful observation of effect of anticoagulants.

Influence on ability to manage motor transport and mechanisms. Special researches concerning influence of drug on ability to manage motor transport and mechanisms were not conducted. However patients should abstain from this activity with vision disorders, to the patients noting drowsiness or other disturbances from the central nervous system.

Side effects:

Below side effects which communication using the drug Movalis®, was regarded as possible are described. Side effects which communication with administration of drug was regarded as possible and which were registered at broad use of drug, are noted by a sign *.

From bodies of a hemopoiesis. Changes of number of blood cells, including changes of a leukocytic formula, a leukopenia, thrombocytopenia, anemia.

From immune system: anaphylactoid/anaphylactic reactions *, other reactions of hypersensitivity immediate типа*.

From the central nervous system.: headache, dizziness, sonitus, drowsiness, confusion of consciousness *, disorientation *, change настроения*.

From digestive tract: perforation of digestive tract, the concealed or explicit gastrointestinal hemorrhage, it is possible from the death, gastroduodenal ulcers, colitis, gastritis *, an esophagitis, stomatitis, an abdominal pain, dyspepsia, diarrhea, nausea, vomiting, a lock, abdominal distention, an eructation, tranzitorny changes of indicators of function of a liver (for example, increase in activity of transaminases or bilirubin), гепатит*.

From skin and skin appendages: toxic epidermal necrolysis *, Stephens-Johnson's syndrome *, ангиоотек *, violent dermatitis *, multiformny erythema *, itch, skin rash, small tortoiseshell, photosensitization.

From a respiratory organs: bronchial asthma.

From cardiovascular system: increase in arterial pressure, heartbeat, feeling of rush of blood to the person.

From urinogenital system: an acute renal failure *, changes of indicators of function of kidneys (increase in level of creatinine and/or urea in blood serum), disturbances of an urination, including an acute ischuria *, intersticial nephrite, a glomerulonephritis, a renal medullary necrosis, nephrotic синдром*.

From organs of sight: conjunctivitis *, vision disorders, including an illegibility зрения*.

General diseases: hypostases.

Interaction with other medicines:

- Other inhibitors of synthesis of prostaglandin, including glucocorticoids and salicylates.

- The concomitant use with meloksikamy increases risk of formation of ulcers in digestive tract and gastrointestinal bleedings (owing to an action synergism) and therefore it is not recommended. The concomitant use with other NPVP is not recommended.

- Selective serotonin reuptake inhibitors - increase in risk of gastrointestinal bleedings.

- Sodium полистирен sulphonate - owing to availability of sorbitol in structure of Movalisa® joint reception can cause risk of development of a necrosis of a large intestine, with possible death.

- Anticoagulants for intake, antitrombotsitrany drugs, heparin for system use, thrombolytic means, inhibitors of the return serotonin reuptake - the concomitant use with meloksikamy increases risk of bleedings owing to inhibition of platelet function.

- Lithium drugs - NPVP increase lithium level in plasma, by means of removal reduction by his kidneys. It is recommended to monitorirovat lithium level during purpose of Movalis® at change of a dose of drugs of lithium and their cancellation.

- A methotrexate - NPVP reduce tubular secretion of a methotrexate, thereby, increasing its concentration in plasma and hematologic toxicity, the methotrexate pharmacokinetics at the same time does not change. In this regard the concomitant use of Movalisa® and a methotrexate in a dosage more than 15 mg/week is not recommended.

The risk of development of interaction between NPVP and methotrexate can take place and at the patients applying a methotrexate in low dosages, especially at patients with a renal failure. Therefore constant control behind number of blood cells and behind function of kidneys is necessary.

At combined use of a meloksikam and methotrexate within 3 days the risk of increase in toxicity of the last increases.

- Contraception - NPVP reduce efficiency of intrauterine contraceptive devices.

- Diuretics - Use of NPVP in case of dehydration of patients is followed by risk of development of an acute renal failure.

- Anti-hypertensive means (beta adrenoblockers, inhibitors angiotensin of the turning enzyme, vazodilatator, diuretics). NPVP reduce effect of anti-hypertensive means, owing to inhibition of prostaglandins having vazodilatiruyushchy properties.

- Antagonists angiotensin-II of receptors at joint appointment with NPVP strengthen decrease in glomerular filtering that thereby, can lead to development of an acute renal failure, especially at patients with a renal failure.

- Holestiramin, connecting meloksika in digestive tract, leads to its more bystry removal.

- NPVP, having effect on renal prostaglandins, can increase nephrotoxicity of cyclosporine.

When using together with meloksikamy medicines which have the known ability to inhibit CYP 2C9 and/or CYP ZA4 (or are metabolized with the participation of these enzymes) it is necessary to take a possibility of pharmacokinetic interaction into account.

It is impossible to exclude a possibility of interaction with anti-diabetic drugs for intake. At simultaneous use of antacids, Cimetidinum, digoxin and furosemide, significant pharmacokinetic interactions it was not revealed.

Contraindications:

- Hypersensitivity to active ingredient or auxiliary components of drug. There is a probability of cross sensitivity to acetylsalicylic acid and other NPVP;
- Symptoms of bronchial asthma, nose polyps, a Quincke's disease or a small tortoiseshell after reception of acetylsalicylic acid or other NPVP in the anamnesis;
- An ulcer illness / perforation of a stomach and duodenum in a stage of an aggravation or recently postponed;
- A disease Krone or ulcer colitis in an aggravation stage;
- Heavy liver failure;
- A heavy renal failure (if the hemodialysis is not carried out);
- Acute gastrointestinal bleedings, recently postponed cerebrovascular bleedings or the established diagnosis of diseases of coagulant system of blood;
- The expressed uncontrollable heart failure;
- Children's age up to 12 years, except for use at a juvenile pseudorheumatism (in case of registration of this indication);
- Pregnancy;
- Breastfeeding;
- Therapy of perioperatsionny pains when performing shunting of coronary arteries (CABG).

With care:
- digestive tract diseases in the anamnesis;
- congestive heart failure;
- renal failure;
- coronary heart disease;
- cerebrovascular diseases;
- dislipidemiya / lipidemia;
- diabetes mellitus;
- diseases of peripheral arteries;
- advanced age;
- long use of NPVP;
- smoking;
- frequent alcohol intake.

Overdose:

The antidote is not known, in case of overdose of drug it is necessary to carry out: evacuation of contents of a stomach and general maintenance therapy. Holestiramin accelerates removal of a meloksikam.

Storage conditions:

Period of validity 3 years. Not to use after the expiry date specified on packaging. Tablets at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 7,5 mg or 15,0 mg. On 10 tablets in the blister from PVH/A1 foil or PVH/PVDH/A1 foil. 1 or 2 blisters together with the application instruction in a cardboard pack.