Meloksikam

General characteristics. Structure:

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

Excipients: starch prezhelatinizirovanny (starch 1500), cellulose microcrystallic, citrate sodium dihydrate, silicon dioxide colloid (aerosil 380), magnesium stearate.

Anesthetic, febrifugal and anti-inflammatory drug, for elimination of symptoms of the inflammatory and progressing joint diseases. Among the non-steroidal anti-inflammatory drugs which are widely used in therapy of joint diseases became meloksika one of the first demanded drugs of selective effect – i.e. having less than side effects.

It differs in high performance in elimination of an inflammation and pain at rather sparing impact on the patient's organism in general. In addition, to meloksika reduces education of the free radicals who are harmful influencing genetics of cells of an organism.

Pharmacological properties:

Pharmacodynamics. Meloksikam - the non-steroidal anti-inflammatory drug possessing anesthetic, antiinflammatory and febrifugal action. Antiinflammatory action is connected with braking of enzymatic 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 prostaglandin which is protecting a mucous membrane of digestive tract and taking part in regulation of a blood-groove in kidneys.

Pharmacokinetics. Absolute bioavailability of a meloksikam – 89% is well soaked up from a GIT (digestive tract). The concomitant use of food does not change absorption. When using drug inside in doses of 7,5 mg and 15 mg of its concentration are proportional to doses. Equilibrium concentration are reached within 3-5 days. At prolonged use of drug (more than 1 year), concentration are similar to those which are noted after the first achievement of an equilibrium state. Linkng with proteins of plasma makes more than 99%. Range of distinctions between the maximum and basal concentration of drug after its reception is rather small once a day and makes when using a dose 7,5 mg 0,4-1,0 mkg/ml, and when using a dose of 15 mg – 0,8–2,0 mkg/ml, (Cmin and Cmax values are given, respectively). Meloksikam gets through gistogematichesky barriers, concentration in synovial fluid reaches 50% of the maximum concentration of drug in plasma.

Almost it is completely metabolized in a liver with formation of four inactive derivatives in the pharmacological relation. 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 3A4 isoenzyme. Peroxidase which activity probably individually varies takes part in formation of two other metabolites (making, respectively, 16% and 4% of drug dose size).

It is removed equally through intestines and kidneys, it is preferential in the form of metabolites. Through intestines in not changed look 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 elimination half-life (T1/2) of a meloksikam makes 15-20 hours. The plasma clearance averages 8 ml/min. At elderly people the clearance of drug decreases. Distribution volume low, also averages 11 l.

The liver or renal failure of moderate severity of influence on pharmacokinetics of a meloksikam essentially does not render.

Indications to use:

Symptomatic treatment of an osteoarthrosis, pseudorheumatism, ankylosing spondylarthritis (Bekhterev's disease) and other inflammatory and degenerative diseases of the joints which are followed by a pain syndrome.

Route of administration and doses:

Drug is accepted inside during food once a day.

The recommended dosing mode:

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

· Osteoarthrosis: 7,5 mg a day. At inefficiency the dose can be increased to 15 mg a day.

· Ankylosing spondylarthritis: 15 mg a day.

The maximum daily dose should not exceed 15 mg.

Patients with the increased risk have development of side effects, and also at the patients with the expressed renal failure who are on a hemodialysis, the dose should not exceed 7,5 mg a day.

Features of use:

It is necessary to be careful at use of drug for patients who have in the anamnesis a peptic ulcer of a stomach and duodenum, and also at the patients who are on treatment by anticoagulants. At such patients the risk of developing of erosive and ulcer gastrointestinal diseases is increased.

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 with the circulatory unefficiency phenomena, at patients with cirrhosis, and also at patients with a hypovolemia as a result of surgical interventions.

At patients with a renal failure if clearance of creatinine more than 25 ml/min., are not required to correction of the mode of dosing.

At the patients who are on dialysis, the dosage of drug should not exceed
7,5 mg/days.

The patients accepting at the same time diuretics and to meloksika have to accept enough liquid.

If in the course of treatment there were allergic reactions (an itch, skin rash, a small tortoiseshell, a photosensitization) it is necessary to see a doctor for the purpose of the solution of a question of the termination of administration of drug.

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

Use of a meloksikam, as well as other drugs blocking synthesis of prostaglandins can influence fertility therefore it is not recommended to the women wishing to become pregnant.

Controls of vehicles, service of cars and mechanisms

Use of drug can cause emergence of undesirable effects in the form of a headache and dizzinesses, drowsiness. It is necessary to refuse control of vehicles and service of the cars and mechanisms demanding concentration of attention.

Side effects:

From the alimentary system: more than 1% - dyspepsia, including nausea, vomiting, abdominal pains, a lock, a meteorism, diarrhea; 0,1-1% - passing increase in activity of "hepatic" transaminases, a hyperbilirubinemia, an eructation, an esophagitis, a gastroduodenal ulcer, bleeding from digestive tract (including hidden), stomatitis; less than 0,1% - perforation of digestive tract, colitis, hepatitis, gastritis.

From bodies of a hemopoiesis: more than 1% - anemia; 0,1-1% - change of a blood count, including a leukopenia, thrombocytopenia.

From integuments: more than 1% - an itch, skin rash; 0,1-1% - a small tortoiseshell; less than 0,1% - a photosensitization, violent rashes, a multiformny erythema, including Stephens-Johnson's syndrome, a toxic epidermal necrolysis.

From respiratory system: less than 0,1% - a bronchospasm.

From a nervous system: more than 1% - dizziness, a headache; 0,1-1% - вертиго, a sonitus, drowsiness; less than 0,1% - confusion of consciousness, a disorientation, emotional lability.

From cardiovascular system: more than 1% - peripheral hypostases; 0,1-1% - increase in the ABP, heartbeat, "inflows" of blood to face skin.

From an urinary system: 0,1-1% - a giperkreatininemiya and/or increase in urea in blood serum; less than 0,1% - an acute renal failure; connection with reception of a meloksikam is not established - intersticial nephrite, an albuminuria, a hamaturia.

From sense bodys: less than 0,1% - conjunctivitis, a vision disorder, including a sight illegibility.

Allergic reactions: less than 0,1% - a Quincke's disease, anaphylactoid/anaphylactic reactions.

Interaction with other medicines:

At simultaneous use with other non-steroidal anti-inflammatory drugs (and also with acetylsalicylic acid) the risk of emergence of erosive cankers and bleedings of a GIT increases.

At simultaneous use with hypotensive drugs, decrease in efficiency of action of the last is possible.

At simultaneous use with drugs of lithium 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 side effect of the last on the hemopoietic system amplifies (danger of developing of anemia and a leukopenia, periodic control of 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 (heparin, тиклопидин, warfarin), and also with thrombolytic drugs (Streptokinasa, fibrinolysin) the risk of development of bleedings increases (periodic control of indicators of coagulability of blood is necessary).

At simultaneous use with Colestyraminum, as a result of binding of a meloksikam, its removal through a GIT amplifies.

At simultaneous use with selective serotonin reuptake inhibitors the risk of development of gastrointestinal bleedings increases.

Contraindications:

· hypersensitivity to active agent or auxiliary components;

· it is contraindicated during the period after performing aortocoronary shunting;

· noncompensated heart failure;

· anamnestic data on an attack of a bronkhoobstruktion, rhinitis, small tortoiseshell after reception of acetylsalicylic acid or other NPVP (the full or incomplete syndrome of intolerance of acetylsalicylic acid – rinosinusit, a small tortoiseshell, polyps of a mucous membrane of a nose, asthma);

· erosive and ulcer changes mucous stomach or 12-perstny gut, active gastrointestinal bleeding;

· inflammatory diseases of intestines (nonspecific ulcer colitis, disease Krone);

· cerebrovascular bleeding or other bleedings;

· the expressed liver failure or an active disease of a liver;

· the expressed renal failure at the patients who are not exposed to dialysis (clearance of creatinine less than 30 ml/min.), the progressing diseases of kidneys, including the confirmed hyperpotassemia;

· pregnancy, breastfeeding period;

· children's age up to 15 years.

With care. Coronary heart disease, cerebrovascular diseases, congestive heart failure, дислипидемия / lipidemia, diabetes mellitus, diseases of peripheral arteries, smoking, clearance of creatinine less than 60 ml/min.

Anamnestic data on development of a canker of a GIT (digestive tract), existence of an infection of Helicobacter pylori, advanced age, long use of NPVP, frequent alcohol intake, heavy somatopathies, the accompanying therapy by the following drugs:

· anticoagulants (for example, warfarin);

· antiagregant (for example, acetylsalicylic acid, klopidogret);

· peroral glucocorticosteroids (for example, Prednisolonum);

· selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline);

For decrease in risk of development of the undesirable phenomena from a GIT it is necessary to use a minimal effective dose minimum possible short course.

Overdose:

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

Treatment: there is no specific antidote; at overdose of drug it is necessary to carry out a gastric lavage, reception of absorbent carbon (within the next hour), symptomatic therapy. Colestyraminum accelerates removal of drug from an organism. The artificial diuresis, urine alkalinization, a hemodialysis – are ineffective because of high communication of drug with blood proteins.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Tablets on 7,5 mg and 15 mg.

On 10 tablets in a blister strip packaging. 1, 2, 3, 4 or 5 blister strip packagings together with the application instruction place in a pack from a cardboard.

On 100 tablets in bank polymeric, each can together with the application instruction is placed in a pack from a cardboard.