Meloksikam-prana

General characteristics. Structure:

Active ingredient: 7,5 mg or 15 mg of a meloksikam in 1 tablet.

Excipients: lactose monohydrate, cellulose microcrystallic, magnesium stearate, starch corn, silicon dioxide colloid, sodium of a kroskarmelloz.

Pharmacological properties:

Pharmacodynamics. Has antiinflammatory, febrifugal and analgeziruyushchy effect. The mechanism of action is caused by inhibition of activity of cyclooxygenase-2 (TsOG-2), participating in biosynthesis of prostaglandins in the field of an inflammation. To a lesser extent to meloksika affects cyclooxygenase-1 (TsOG-1) participating in synthesis of the prostaglandins which are protecting a mucous membrane of the digestive tract (DT) and taking part in regulation of a blood-groove in kidneys.
 
Pharmacokinetics. Absorption. It is well soaked up from a GIT. Absolute bioavailability of a meloksikam - 89%. The concomitant use of food does not influence absorption. Concentration of a meloksikam at administration of drug inside in doses of 7.5 mg and 15 mg is proportional to a dose.

Distribution. The equilibrium state is reached within 3-5 days of regular reception. At long (more than 1 year) drug use equilibrium concentration of a meloksikam in plasma is similar to equilibrium concentration (Css) which was established after the first days of administration of drug. Linkng with proteins of plasma makes more than 99%. At administration of drug of 1 times/days the minimum equilibrium concentration _(Cssmin) and the maximum equilibrium concentration _(Cssmax) differ in small degree and make at reception 7.5 mg 0.4-1.0 mkg/ml, and at reception of 15 mg – 0.8-2.0 mkg/ml respectively. Meloksikam gets through gistogematichesky barriers, concentration in synovial fluid reaches 50% of the maximum concentration _(Cmax) in plasma. The volume of distribution (Vd) averages 11 l.

Metabolism. Meloksikam is almost completely metabolized in a liver with formation of four pharmacological inactive metabolites. The basic is to 5-karboksimeloksika which is formed by oxidation of an intermediate metabolite (5-gidroksimetilmeloksikam). At the researches in vitro it is established that biotransformation occurs with the participation of an isoenzyme CYP2C9, additional value has CYP3A4 isoenzyme. In образованиидвух other metabolites peroxidase which activity probably individually varies takes part.

Removal. It is removed equally with a stake and urine, it is preferential in the form of metabolites (to 5-karboksimeloksika - to 60%, to 5-gidroksimetilmeloksika - 9%, and two others - 16% and 4% respectively). With a stake in not changed look less than 5% of a daily dose are removed, in urine in not changed look drug is found only in trace quantities. An elimination half-life (T1/2) - 15-20 h. The plasma clearance averages 8 ml/min.

Pharmacokinetics in special clinical cases. At elderly people the clearance of drug decreases.

At patients with a liver or renal failure of moderate severity the pharmacokinetics of a meloksikam significantly does not change.

Indications to use:

Symptomatic therapy:
— osteoarthrosis;
— pseudorheumatism;
— ankylosing spondylitis (Bekhterev's disease).

It is intended for symptomatic therapy, reduction of pain and an inflammation at the time of use, does not influence progressing of a disease.

Route of administration and doses:

At a pseudorheumatism the recommended dose makes 15 mg/days; depending on therapeutic effect the dose can be lowered to 7.5 mg/days.

At an osteoarthrosis drug appoint 7.5 mg/days in a dose, in the absence of effect the dose can be raised to 15 mg/days.

At an ankylosing spondylitis the daily dose makes 15 mg. The maximum daily dose should not exceed 15 mg.

Drug is accepted by 1 times/days during meal.

Patients with the increased risk have development of side effects, and also at the patients with the expressed renal failures (KK less than 30 ml/min.) who are on a hemodialysis, the dose should not exceed 7.5 mg/days.

With renal failures (KK more than 30 ml/min.) correction of the mode of dosing is not required from patients.

Features of use:

It is necessary to be careful at use of drug for the patients having a peptic ulcer of a stomach and duodenum in the anamnesis and for the patients receiving anticoagulating therapy since at this category of patients it is raised risk of development of erosive cankers of a GIT.

It is necessary to be careful and control indicators of function of kidneys at use of drug for patients of advanced age, patients with chronic heart failure, at patients with cirrhosis, and also at patients with a hypovolemia as a result of surgical interventions.

The patients who are at the same time accepting diuretics and to meloksika have to receive enough liquid.

At emergence of allergic reactions (an itch, skin rash, a small tortoiseshell, a photosensitization) it is necessary to stop administration of drug.

Meloksikam, also as well as other NPVP, can mask symptoms of infectious diseases.

Influence on ability to driving of motor transport and to control of mechanisms. Against the background of drug use the patient should not be engaged in potentially dangerous types of activity requiring special attention since developing of a headache, dizziness, drowsiness is possible.

Side effects:

Frequency: often – more than 1%; infrequently – 0.1-1%; seldom – 0.01-0.1%; very seldom – less than 0.01%.

From the alimentary system: often – dyspepsia, including nausea, vomiting, abdominal pains, a lock, a meteorism, diarrhea; infrequently – passing increase in activity of "hepatic" transaminases, a hyperbilirubinemia, an eructation, an esophagitis, a gastroduodenal ulcer, bleeding from a GIT (including hidden), stomatitis; seldom – perforation of a GIT, colitis, hepatitis, gastritis.

From cardiovascular system: often – peripheral hypostases, infrequently – tachycardia, increase in the arterial pressure (AP), feeling of "inflows".

From respiratory system: seldom – an aggravation of a course of bronchial asthma.

From the central nervous system (CNS): often – a headache, dizziness; infrequently – вертиго, a sonitus, drowsiness; seldom – a disorientation, confusion of consciousness, emotional lability.

From an urinary system: infrequently – a giperkreatininemiya and/or increase in concentration of urea in blood serum; seldom – an acute renal failure; connection with reception of a meloksikam is not established – intersticial nephrite, an albuminuria, a hamaturia.

Dermatological reactions: often – an itch, skin rash; infrequently – a small tortoiseshell, it is rare – the increased photosensitivity, violent rashes, a mnogoformny erythema, including Stephens-Johnson's syndrome, a toxic epidermal necrolysis.

From system of a hemopoiesis: often – anemia; infrequently – a leukopenia, thrombocytopenia.

Allergic reactions: seldom – anaphylactoid reactions (including an acute anaphylaxis), hypostasis of lips and language, an allergic vasculitis.

Others: fever.

Interaction with other medicines:

At simultaneous use with other NPVP (including with acetylsalicylic acid) the risk of emergence of erosive cankers and bleedings of a GIT increases.

At simultaneous use with anti-hypertensive drugs decrease in efficiency of action of the last is possible.

At simultaneous use with drugs of lithium development of cumulation of lithium and increase in its toxic action is possible (control of concentration of lithium in blood is recommended).

At simultaneous use with a methotrexate the probability of developing of anemia and a leukopenia increases (periodic performing the general blood test is shown).

At simultaneous use with diuretics and with cyclosporine the risk of development of a renal failure increases.

At simultaneous use with intrauterine contraceptive means decrease in efficiency of action of the last is possible.

At simultaneous use with anticoagulants (including with heparin, warfarin), and also with thrombolytic drugs (including with Streptokinasa, fibrinolysin) the risk of development of bleedings increases (periodic control of indicators of coagulability of blood is necessary).

At simultaneous use with Colestyraminum removal of a meloksikam through a GIT increases (due to binding).

Contraindications:

- hypersensitivity (including to NPVP of other groups);
- a full or incomplete combination of bronchial asthma, the nose recuring a polypose and about nasal bosoms and intolerance of acetylsalicylic acid, etc. NPVP;
- a peptic ulcer of a stomach and duodenum in an aggravation phase;
- inflammatory diseases of intestines;
- bleeding of various genesis (including from a GIT, cerebrovascular);
- a heavy renal failure – the clearance of creatinine (CC) less than 30 ml/min. (if the hemodialysis is not carried out);
- the progressing diseases of kidneys;
- heavy liver failure or active disease of a liver;
- heavy heart failure;
- the bronchial asthma caused by reception of acetylsalicylic acid;
- the confirmed hyperpotassemia;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
- children's age up to 12 years;
- pregnancy;
- lactation (breastfeeding);
- hypersensitivity to drug components.

With care. Advanced age, the coronary heart disease (CHD), the chronic heart failure (CHF), cerebrovascular diseases, дислипидемия / a lipidemia, a diabetes mellitus, diseases of peripheral arteries, smoking, KK of 30-60 ml/min., GIT cankers in the anamnesis, existence of an infection of N. of pylori, long use NPVP, alcoholism, heavy somatopathies, a concomitant use of peroral glucocorticosteroids (GKS) (including Prednisolonum), anticoagulants (including warfarin), antiagregant (including klopidogret), selective serotonin reuptake inhibitors (including a tsitaloprama, fluoxetine, a paroksetin, sertraline). For rectal administration (in addition): inflammatory diseases of a rectum and proctal department, rectal or proctal bleeding (including in the anamnesis).

Overdose:

Symptoms: consciousness disturbance, nausea, vomiting, pains in epigastriums, bleeding from a GIT, an acute renal failure, an acute liver failure, an apnoea, an asystolia.

Treatment: a gastric lavage, reception of absorbent carbon (during 1 h after administration of drug); if necessary carry out symptomatic therapy. Colestyraminum accelerates removal of a meloksikam from an organism. The artificial diuresis, urine alkalinization, a hemodialysis are ineffective because of high extent of linkng of a meloksikam with blood proteins. There is no specific antidote.

Storage conditions:

List B. To store in the dry, protected from light place, at a temperature not over 25 to °s.khranit in the places unavailable to children. Not to use after the period of validity specified on packaging. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 7,5 and 15 mg. On 10 tablets in a blister strip packaging or on 50, 60, 70, 80, 90, 100 tablets in a polymeric can. Packaging 70, 80, 90, 100 tablets – for hospitals. Each can or 1, 2, 3 or 4 blister strip packagings together with the application instruction are placed in a pack from a cardboard.