Meloksikam Orion

General characteristics. Structure:

Active ingredient: 7,5 mg or 15,0 mg of a meloksikam.

Excipients: cellulose microcrystallic, starch corn prezhelatinizirovanny, lactoses monohydrate, corn starch, sodium citrate, silicon dioxide colloid anhydrous, magnesium stearate.

Non-steroidal anti-inflammatory drug with anesthetics and febrifugal properties from group of oksikam.

Pharmacological properties:

Pharmacodynamics. Meloksikam is a non-steroidal anti-inflammatory drug with anesthetics and febrifugal properties from group of oksikam. Antiinflammatory activity of a meloksikam was shown on classical models of an inflammation. As well as in a case with other NPVP, the exact mechanism of its action is not known. In total NPVP (including meloksika) possess, at least, one known mechanism of action: they inhibit biosynthesis of prostaglandins — inflammation mediators.

Pharmacokinetics. Drug is easily absorbed in a GIT. After a single dose of a meloksikam average maximum concentration in a blood plasma is reached in 5–6 h. At continuous use equilibrium concentration is reached in 3–5 days. At use of 1 times a day concentration of drug in a blood plasma varies a little, that is 0,4–1,0 mkg/ml at a dose of 7,5 mg and 0,8–2,0 mkg/ml at a dose of 15 mg (the minimum and maximum concentration at equilibrium concentration). The maximum equilibrium concentration of drug in a blood plasma is reached in 5–6 h after reception of a tablet. After continuous treatment more than one year concentration of drug is similar to that which was noted at the time of achievement of an equilibrium state after an initiation of treatment. The concomitant use of food does not influence absorption of a meloksikam.

Meloksikam substantially contacts proteins of a blood plasma (99% with albumine). Drug gets into synovial fluid where its concentration makes about a half of concentration in a blood plasma. The volume of distribution is small, on average 11 l. Fluctuation of indicators at different patients makes about 30-40%.

Meloksikam biotransformirutsya substantially in a liver. In urine define four pharmakodinamichesk inactive a metabolite of a meloksikam. The main metabolite — 5 -karboksimeloksikam (60% of a dose) — is formed at oxidation of an intermediate metabolite — 5 -gidroksimetilmeloksikama. This intermediate metabolite is also allocated, though to a lesser extent (9% of a dose). According to the researches in vitro, CYP 2C9 plays the main role in a metabolic way whereas CYP 3A4 isoenzyme plays a smaller role. Activity of peroxidase of the patient influences formation of two other metabolites. They make respectively 16 and 4% of the accepted dose.

Meloksikam is allocated generally in the form of metabolites. Metabolites equally reveal in urine and Calais. About 5% of a daily dose of drug in not changed look are removed with a stake and only in very small amounts — with urine. The elimination half-life makes about 20 h. The general plasma clearance averages 8 ml/min.

The pharmacokinetics of a meloksikam is linear within a dose of 7,5-15 mg after peroral and introduction in oil.

Special categories of patients. Liver/renal failure. The liver or renal failure of easy or moderate degree has no significant effect on pharmacokinetics of a meloksikam. As the bigger volume of distribution at terminal degree of a renal failure can increase concentration of a meloksikam, it is not necessary to exceed a daily dose — 7,5 mg.

Patients of advanced age: the average plasma clearance in equilibrium standing was slightly lower at patients of advanced age, than at young people.

Indications to use:

Short-term symptomatic treatment of aggravations of an osteoarthrosis. Prolonged symptomatic treatment of a pseudorheumatism and ankylosing spondylitis.

Route of administration and doses:

At adults and children 15 years are aged more senior use drug inside in such doses.

Osteoarthrosis aggravation: 7,5 mg/days. If the condition of the patient does not improve, if necessary the dose can be raised to 15 mg/days.

The pseudorheumatism ankylosing a spondylitis: 15 mg/days. The dose can be lowered to 7,5 mg/days.

The general daily dose should be accepted once during food, washing down with water or other liquid. It is not necessary to exceed a dose of 15 mg/days.

As the risk connected using a meloksikam can increase with increase in a dose and duration of reception, drug should be used during as it is possible the smaller period and in the minimum effective daily dose. Periodically it is necessary to estimate therapeutic effect for the purpose of determination of duration of use that especially concerns patients with an osteoarthrosis.

Special categories of patients. Patients of advanced age and patients with the increased risk of side effects. Patients of advanced age have a recommended daily dose for treatment of a pseudorheumatism and an ankylosing spondylitis makes 7,5 mg. If the patient has an increased risk of side effects, treatment should be begun with a daily dose – 7,5 mg.

Renal failure. The daily dose for the patient who is on a hemodialysis in connection with a heavy renal failure should not exceed 7,5 mg.

For patients with a renal failure easy or moderate severity (clearance of creatinine more than 25 ml/min.) dose adjustment is not required.

Liver failure. For patients with a liver failure of easy or average degree in dose adjustment there is no need.

Features of use:

If the patient in the anamnesis had instructions on an esophagitis, gastritis and/or a round ulcer of a stomach or duodenum, before therapy meloksikamy it is necessary to conduct gastroenterological examination (to be convinced of their full treatment). For prevention of a recurrence of these diseases it is necessary to control a condition of such patients during therapy meloksikamy.

Patients with symptoms of a disease of a digestive tract or that disease (for example ulcer colitis, a disease Krone) have to be in the anamnesis under careful observation in connection with danger of emergence of disturbances of digestion and especially gastrointestinal bleeding.

As well as in case of use of other NPVP, at reception of a meloksikam it was reported about emergence of gastrointestinal bleedings or ulcers / перфораций. These reactions arose at any stages of treatment with/without symptoms harbingers at patients with a serious gastrointestinal illness in the anamnesis, and also at patients without those in the anamnesis. Gastrointestinal bleeding or ulcer/perforation in general are more serious at people of advanced age.

If the patient receiving to meloksika has a gastrointestinal bleeding, drug should be cancelled.

NPVP, including oksikama, as we know, can be associated with potentially heavy skin reactions and heavy, life-threatening, hypersensitivity reactions (for example anaphylactic). In such cases it is necessary to stop immediately use of a meloksikam and to carefully observe a condition of the patient.

In some cases NPVP can cause intersticial nephrite, a glomerulonephritis, a renal medullary necrosis or a nephrotic syndrome.

The majority of NPVP can cause temporary increase in concentration of serumal transaminases, increase in level of bilirubin in blood serum and other indicators of function of a liver, and also increase in level of creatinine and an urea nitrogen. Reported also about other deviations in laboratory tests. These deviations usually were reversible and poorly expressed. If these deviations are considerable or long, use of a meloksikam should be stopped, and the patient needs to conduct examination.

Use of NPVP can be associated with a delay of sodium, potassium and water, and also with disturbance of natriuretic effect of diuretics that can lead to increase in expressiveness of symptoms of heart failure or AG.

NPVP inhibit renal synthesis of prostaglandin that is connected with preservation of renal perfusion at patients with an insufficient renal blood-groove and reduced OTsK. In such cases reception of NPVP can aggravate a latent renal failure. However renal function is recovered after the treatment termination. The risk of emergence of insufficiency extends to patients of advanced age and patients with symptoms of heart failure, cirrhosis, a nephrotic syndrome or a disease of kidneys, and also the patients who are accepting diuretics or who transferred serious surgical intervention which led to reduction of OTsK. At such patients it is necessary to control carefully secretory function of kidneys (mocheotdeleniye).

The elderly or weakened patients transfer by-effects often worse. Therefore such categories of patients demand careful observation. As well as in a case with other NPVP, extra care should be observed at treatment of patients of advanced age with renal, liver or heart failure.

The maximum daily dose should not be exceeded even in the absence of proper therapeutic response. It is not necessary to accept at the same time other NPVP as it can increase their toxicity, at the same time the therapeutic effect was not proved. If the condition of the patient does not improve in several days of therapy, it is necessary to estimate clinical advantage and adequacy to the carried-out therapy.

Meloksikam and other NPVP can mask symptoms of the existing infectious disease.

Use of a meloksikam (and other drugs inhibiting synthesis of cyclooxygenase or prostaglandin) can reduce fertility therefore it is not recommended to the women planning pregnancy. It is necessary to approach with care purpose of a meloksikam to women with infertility or which undergo inspection concerning infertility.

This medicine contains lactoses monohydrate. Patients with rare hereditary intolerance of a galactose, insufficiency of lactase of Lapp or malabsorption of glucose galactose should not accept this drug.

It is recommended to avoid reception of a meloksikam in I and II trimesters of pregnancy. In the last trimester of pregnancy any inhibitor of synthesis of prostaglandins can lead to development of cardiopulmonary complications in a fruit (pulmonary hypertensia with premature closing of an arterial channel) and renal toxicity, or reduction of a uterus can oppress. This impact on a uterus can cause bad contractility of a uterus in labor or cause a delay of childbirth that was noted in the researches conducted on animals. Therefore all NPVP are absolutely contraindicated in the III trimester of pregnancy.

NPVP get into breast milk therefore as a preventive action mothers nursing should avoid reception of this drug.

Influence on ability to manage vehicles and to work with mechanisms. Special researches of impact on ability to manage vehicles and to work with mechanisms did not carry out. However on the basis of pharmakodinamichesky characteristics and messages on by-effects it is established what to meloksika does not influence these abilities, or this influence is very insignificant. At emergence of visual disturbances, drowsiness, dizziness or other phenomena from TsNS, it is recommended to refrain from the activity demanding bystry psychomotor reactions.

Side effects:

There are messages on the following side effects which can be connected using a meloksikam which frequency of emergence is based on results of clinical trials.

Also post-marketing messages on by-effects which can be connected with reception of a meloksikam are considered.

Side effects are given below according to the frequency of their emergence:

very often (≥1/10), it is frequent (≥1/100, ≤1/10), sometimes (≥1/1000, ≤1/100), is rare (≥1/10 000, ≤1/1000) and is very rare (≤1/10 000).

System of a hemopoiesis and lymphatic system: often — anemia; sometimes — disturbance of indicators of a gemogramma: leykotsitopeniya, thrombocytopenia, agranulocytosis.

Immune system: seldom — anaphylactic reactions.

Mental disorders: seldom — differences of mood, sleeplessness, dreadful dreams.

TsNS: often — dizziness, a headache; sometimes — вертиго, a ring in ears, drowsiness; seldom — confusion of consciousness.

Organ of sight: seldom — visual disturbances, including an image vagueness.

Cardiovascular system: sometimes — a cardiopalmus, increase in the ABP, inflows.

Respiratory organs: seldom — attacks OH at persons with hypersensitivity to acetylsalicylic acid or other NPVP.

GIT: often — dyspepsia, nausea and vomiting, an abdominal pain, a meteorism, diarrhea; sometimes — gastrointestinal bleeding, a round ulcer, an esophagitis, stomatitis; seldom — a gastrointestinal perforation, gastritis, colitis. The round ulcer, gastrointestinal bleeding or a perforation can sometimes be serious, especially at people of advanced age.

Gepatobiliarny disturbances: sometimes — reversible increase in indicators of function of a liver (for example hepatic transaminases, bilirubin); seldom — hepatitis.

Skin and hypodermic cellulose: often — an itch, skin rash; sometimes — a small tortoiseshell; seldom — Stephens's syndrome — Johnson and a toxic epidermal necrolysis, a Quincke's disease, violent reactions, such as a multiformny erythema, photosensitivity reactions.

Urinary system: sometimes — disturbance of indicators of function of kidneys (for example creatinine, urea); seldom — a renal failure.

The general symptoms and disturbances connected with an injection site: often — hypostases, including hypostasis of the lower extremities.

Information of rather separate serious and/or often arising side effects. There are messages on separate cases of development of an agranulocytosis in the patients receiving treatment meloksikamy and other potentially miyelotoksichny drugs.

Interaction with other medicines:

Pharmakodinamichesky interactions: other NPVP, including salicylates (acetylsalicylic acid of 3 g/days): simultaneous use of several NPVP can increase the frequency of emergence of cases of gastrointestinal ulcers and bleeding owing to synergy effect. Simultaneous use of a meloksikam and other NPVP is not recommended.

Diuretics: treatment of NPVP can cause an acute renal failure, especially in patients with symptoms of dehydration.

The patients accepting to meloksika and diuretics have to receive enough liquid, and before an initiation of treatment at them it is necessary to define functions of kidneys.

Peroral anticoagulants: the risk of bleeding increases owing to inhibition of function of thrombocytes and damage mucous a GIT. Simultaneous use of peroral anticoagulants and NPVP is not recommended.

At impossibility to avoid such combination it is necessary to watch carefully an indicator INI (the international normalized index).

Trombolitiki and inhibitors of aggregation of thrombocytes: the risk of bleeding is increased owing to inhibition of function of thrombocytes and injury of a mucous membrane of a GIT.

APF inhibitors and antagonists of a receptor of angiotensin II: NPVP (including acetylsalicylic acid in a dose of 3 g/days) and antagonists of a receptor of angiotensin II have synergy effect, reducing glomerular filtering that is especially dangerous at insufficiency of function of kidneys. And/or at patients with dehydration this combination can cause OPN in elderly people, influencing directly glomerular filtering. At the beginning of therapy monitoring of function of kidneys is recommended. Patients have to monitor sufficient consumption of liquid carefully. Besides, the concomitant use of these drugs can reduce anti-hypertensive effect of APF inhibitors and antagonists of a receptor of angiotensin II, that is drug becomes only partially effective that is caused by inhibition of synthesis of vasodilating prostaglandins.

Other anti-hypertensive drugs (for example blockers of β-adrenoceptors)))))))))): the anti-hypertensive effect of blockers of β-adrenoceptors can decrease that is caused by inhibition of synthesis of vasodilating prostaglandins.

Cyclosporines: NPVP can increase renal toxicity of cyclosporine that is caused by their action on prostaglandins of kidneys. At a concomitant use of these drugs it is necessary to control a condition of function of kidneys. It especially concerns patients of advanced age.

Glucocorticoids: GKS applied along with NPVP can increase the frequency of emergence of by-effects from a GIT.

Intrauterine contraceptives: there are messages that NPVP reduce efficiency of intrauterine contraceptives, but it demands further researches.

Pharmacokinetic interactions (impact of a meloksikam on pharmacokinetics of other drugs).

Lithium: there are messages that NPVP increase concentration of lithium in blood serum (by decrease in removal of lithium kidneys). Concentration of lithium can reach level, life-threatening. Simultaneous use of lithium and NPVP is not recommended. If the combination of these drugs is necessary, in the beginning during the carrying out and cancellation of therapy meloksikamy it is necessary to control concentration of lithium in a blood plasma.

Methotrexate: NPVP can reduce canalicular secretion of a methotrexate, thereby increasing its concentration in a blood plasma. If the patient receives a high dose of a methotrexate (more than 15 mg/week), simultaneous use of NPVP is not recommended.

It is necessary to consider risk of interaction between NPVP and a methotrexate at the patients accepting low doses of a methotrexate, especially if patients have symptoms of a renal failure. In need of a combination therapy it is necessary to control indicators of a gemogramma and function of kidneys and to be careful at use of NPVP. In such cases concentration of a methotrexate in a blood plasma can increase that will lead to strengthening of toxic effects.

Though parallel use of a meloksikam has no significant effect on methotrexate pharmacokinetics (15 mg/week), it is necessary to consider that at such therapy hematologic toxicity of a methotrexate can increase.

Pharmacokinetic interactions (influence of other drugs on pharmacokinetics of a meloksikam):

Colestyraminum: Colestyraminum accelerates removal of a meloksikam, interfering with enterohepatic blood circulation owing to what the clearance of a meloksikam increases by 50%, and the elimination half-life decreases to 13±3 h. This interaction has clinical value.

CYP 3A4 and CYP 2C9 inhibitors, inductors and substrates: at purpose of a meloksikam along with the drugs inhibiting CYP 3A4 and/or CYP 2C9 enzymes and the metabolized these enzymes, it is necessary to consider potential pharmacokinetic interactions.

Clinically significant pharmacokinetic medicinal interactions at a concomitant use with antacids, Cimetidinum or digoxin were not noted. However concentration of digoxin in blood serum at the combined use can increase.

Contraindications:

Use of this medicine is contraindicated in such cases:

• hypersensitivity to a meloksikam, any of components of drug, NPVP of this kind or to acetylsalicylic acid. Patients in whose anamnesis are noted OH, nose polyps, a Quincke's edema or a small tortoiseshell after reception of acetylsalicylic acid or other NPVP should not appoint tablets;

• period of pregnancy and feeding by a breast;

• active now or in the anamnesis a recurrent round ulcer of a stomach or duodenum;

• heavy degree of a liver failure;

• heavy degree of a renal failure at which the patient is not on a hemodialysis;

• the gastrointestinal bleeding, cerebral and vascular bleeding or other frustration connected with bleeding;

• heavy dekompensirovanny heart failure;

Meloksikam it is not necessary to apply to treatment of children and teenagers 15 years are aged younger.

Overdose:

The lethargy, drowsiness, nausea, vomiting and pain in epigastriums usually belong to symptoms of acute overdose of NPVP. These symptoms usually are eliminated by means of a maintenance therapy. Perhaps zheludocho-intestinal bleeding. The expressed toxicity can lead to AG, OPN, a liver failure, oppression of respiratory function, a coma, spasms, vascular insufficiency and a cardiac standstill. There are messages on the anaphylactic reactions which developed against the background of reception of NPVP accepted according to recommendations. These reactions are also possible at overdose.

In overdose cases the symptomatic and maintenance therapy is shown to the patient. In clinical trial removal of a meloksikam accelerated at reception by the patient of 4 g of Colestyraminum 3 times a day.

Storage conditions:

To store at the room temperature (15–25 °C) in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 1 blister or on 3 blisters in a cardboard box.