Astator 10

General characteristics. Structure:

Active ingredient: 10 mg of montelukast in the form of sodium montelukast.

Excipients: mannitol (Е 421), cellulose microcrystallic, sodium of a kroskarmelloz, aspartame (Е 951), fragrance cherry, ferrous oxide red (Е 172), ferrous oxide yellow (Е 172), magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Cisthienyl-leukotrienes (LTC4, LTD4, LTE4) are powerful eicosanoids of an inflammation which are emitted with various cells, including opasisty cells and eosinophils. These important pro-asthmatic mediators contact tsisteinil-leukotriene receptors (CysLT) which are present at respiratory tracts of the person (including myocytes of smooth muscles and macrophages), and other cells прозапалення (including eosinophils and some myeloid stem cells). CysLT are related to a pathophysiology of asthma and allergic rhinitis. At asthma leykotriyenozavisimy effects include a bronchospasm, expectoration, permeability of vessels and increase in quantity of eosinophils. At allergic rhinitis after exposure with CysLT allergen it is released from a nasal mucous membrane during both phases (early and late) and shown by symptoms of allergic rhinitis. At intranasal test with CysLT increase in resistance of pneumatic nasal ways and symptoms of nasal obstruction was shown.

Montelukast is active connection which with sharp selectivity and chemical affinity contacts CysLT1-receptors. Montelukast causes considerable blocking cisthienyl - leukotriene receptors of respiratory tracts that was confirmed with its ability to inhibit the bronkhokonstriktion at asthmatic patients caused by inhalation of LTD4. Even the low dose of 5 mg causes considerable blockade of stimulated LTD4 of a bronkhokonstriktion. Montelukast causes a bronkhodilatation a current of 2 hours after oral administration, this effect was the additive to the bronkhodilatation caused by β-agonists..........

Treatment by montelukast suppresses a bronchospasm both on early, and at a late stage, reducing reaction to antigens. Montelukast in comparison with placebo, reduces number of eosinophils of peripheral blood at adult patients and children. During the researches it is shown that montelukast reception considerably reduced number of eosinophils in respiratory tracts (on measurements of a phlegm).

Pharmacokinetics. Absorption. After reception montelukast is quickly and almost completely soaked up. At adults at reception on an empty stomach of tablets in a dose of 10 mg the maximum concentration (Cmax) in a blood plasma is reached in 3 h (Tmakh). Average bioavailability makes 64%. Reception of usual food does not influence Cmax in a blood plasma and bioavailability of tablets. Safety and efficiency were shown during the researches in groups where a pill of 10 mg was taken irrespective of the use of food.

Distribution. More than 99% of montelukast contact proteins of a blood plasma. The volume of distribution of montelukast in a stationary phase averages from 8 to 11 l. At a research of the passing montelukast marked with a radioisotope through a blood-brain barrier was minimum. In all other fabrics of concentration of the drug marked with a radioisotope in 24 hours after reception of a dose also were minimum.

Metabolism. Montelukast is actively metabolized. During the researches using therapeutic doses of concentration of metabolites to montelukast in steady state of a blood plasma at adults and patients of children's age are not defined.

During the researches in vitro with use of microsomes of a liver of the person it is proved that tsitokhrom of P450 ZA4, 2A 6 and 2C9 take part in metabolism to montelukast. On the basis of results of further researches of microsomes of a liver of the person of in vitro it is shown that in therapeutic concentration montelukast does not suppress a tsitokhroma of P450 ZA4, 2C9, 1A2, 2A6, 2C19 and 2D6. Participation of metabolites in therapeutic actions to montelukast is minimum.

Conclusion. The clearance to montelukast from a blood plasma of healthy adult volunteers averages 45 ml/min. After a peroral dose marked by isotope to montelukast of 86% it is removed with a stake for 5 days and less than 0,2% – with urine. In total with bioavailability to montelukast at peroral appointment this fact specifies that its metabolites are almost completely removed with bile.

Pharmacokinetics at different groups of patients. For patients of advanced age, and also patients with a liver failure easy and moderate severity dose adjustment is not necessary. Researches for patients with a renal failure were not conducted. As montelukast and its metabolites are removed with bile, dose adjustment for patients with a renal failure is not considered necessary. To montelukast patients with a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu) have no data on character of pharmacokinetics.

At reception of high doses of montelukast (that in 20 and 60 times exceeded the dose recommended for adults) decrease in concentration of theophylline in plasma was observed. This effect is not observed at reception of the recommended dose of 10 mg of 1 times a day.

Indications to use:

Additional treatment of bronchial asthma at patients with persistent asthma from easy to average degree that is insufficiently controlled by inhalation corticosteroid drugs, and also at insufficient clinical control of asthma by means of the β-agonists of short action applied as necessary. A symptomatic treatment of seasonal allergic rhinitis at patients with bronchial asthma.

Prevention of asthma which dominating component is the bronchospasm induced by exercise stresses.

Relief of symptoms of seasonal and year-round allergic rhinitis.

Route of administration and doses:

Drug is used to adults and children 15 years are more senior. Patients with asthma and allergic rhinitis (seasonal and year-round) need to accept on 1 tablet 10 mg of 1 times a day.

For treatment of asthma or asthma in combination with seasonal allergic rhinitis adults and children age of 15 years need to take 1 pill of 10 mg of 1 times a day, in the evening.

For relief of symptoms of allergic rhinitis time of reception is selected individually. Correction of a dose for patients of advanced age, and also for patients with a liver failure of easy or moderate degree a renal failure is not required.

Data on dose adjustment for patients with heavy degree of a liver failure are absent.

Patients with a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu) have no data on character of pharmacokinetics of montelukast therefore recommendations about dose adjustment are absent. The dosage of drug is identical to male and female patients.

Children. Apply to children age of 15 years. Children aged up to 15 years should use drug in the form of chewable tablets.

Features of use:

Patients need to be warned that Astator 10 should not be applied to removal of bad asthmatic attacks. It is recommended to continue treatment by usual corresponding preparta for removal of attacks. In case of a bad attack it is necessary to apply inhalation β-agonists of short action. Patients need to consult as soon as possible with the doctor if it is required to them bigger, than usually, the number of inhalations by β-agonists of short action.

It is not necessary to replace sharply with montelukast therapy by inhalation or peroral corticosteroid drugs. In rare instances the patients receiving antiasthmatic means, including montelukast can have a system eosinophilia, sometimes together with clinical manifestations of a vasculitis, a so-called syndrome of Charg-Strausa (a granulematozny allergic angiitis) which treatment is carried out by means of system corticosteroid therapy. Such cases usually (but not always) were connected with reduction or cancellation of therapy by corticosteroid drugs. It is impossible neither to disprove probability that antagonists of leukotriene receptors can be connected with emergence of a syndrome of Charg-Strausa, nor to confirm therefore doctors need to be warned about possibility at patients of an eosinophilia, vaskulitny rash, deterioration in pulmonary symptomatology, a complication from cordial system and/or neuropathy. Patients at whom above-mentioned symptoms developed need to undergo repeated inspection, and the scheme of their treatment should be revised.

Astator 10 contains aspartame which is a phenylalanine source. To the patients sick with a fenilketonuriya, it is necessary to consider that 1 tablet of 4 mg contains phenylalanine in the quantity equivalent to a dose of phenylalanine of 0,674 mg.

General recommendations about drug use. Therapeutic effect of drug concerning control of asthmatic parameters continues during the day. Administration of drug is not connected with the use of food. Patients should recommend to continue administration of drug, even when asthma is controlled, and also during an aggravation of the asthmatic status. It is not necessary to accept drug together with the medicines which are also containing montelukast.

Drug can be added to the existing course of treatment of the patient.

Inhalation corticosteroids. Astator 10 patients who have inhalation corticosteroids together with β-agonists of short action applied if necessary can apply as additional treatment do not provide satisfactory clinical control of a disease.

It is not necessary to replace inhalation corticosteroids with drug Astator 10.

Reduction of the accompanying therapy. Treatment by bronchial spasmolytics. Astator 10 it is possible to add to the scheme of treatment of patients whose condition is not controlled properly only by bronchial spasmolytics. When the clinical effect occurs, (as a rule, after the first dose), broncholitic therapy can be reduced before the use as necessary.

Inhalation corticosteroids. Treatment by drug Astator 10 provides additional clinical benefits for the patients receiving inhalation corticosteroids. Reduction of a dose of corticosteroids is possible in the presence of control over a disease. The dose should be reduced gradually under medical observation. For some patients inhalation corticosteroids can be cancelled completely. Astator 10 it is not necessary to replace with drug inhalation corticosteroids sharply.

Use during pregnancy or feeding by a breast. Use of drug during pregnancy was not studied. It is unknown whether drug gets into breast milk. At purpose of drug women during pregnancy or feeding by a breast need to consider a ratio advantage/risk.

According to international marketing experience, at children whose mothers accepted drug during pregnancy inborn defects of extremities were occasionally observed. Most of these women accepted as well other drugs from asthma. The causal relationship between these cases and administration of drug is not proved.

Ability to influence speed of response at control of motor transport or other mechanisms. Influence to montelukast on ability to drive the car or other mechanisms is not expected. However in isolated cases certain patients can have a dizziness or drowsiness therefore during administration of drug it is necessary to abstain from driving or other mechanisms.

Side effects:

Infections and invasions: upper respiratory tract infections.

From a nervous system: headache.

From a digestive tract: abdominal pain.

General frustration: thirst.

The side reactions registered in the post-marketing period

From system of blood: tendency to strengthening of bleeding.

From immune system: hypersensitivity reactions, including anaphylaxis, eosinophilic infiltration of a liver.

From mentality: sleep disorders, including nightmares, hallucinations, sleeplessness, irritability, anger, impatience, excitement, including an agressive behavior or hostility, a tremor, depressions, a disorientation; very seldom – suicide intentions and behavior (suitsidalnost).

From a nervous system: slackness and dizziness, paresthesia / гипоэстезия, attacks.

From cardiovascular system: heart consciousness.

From a digestive tract: diarrhea, dryness in a mouth, dyspepsia, nausea, vomiting.

From gepatobiliarny system: increase in levels of transaminases of serum (ALT, nuclear heating plant), hepatitis (cholestatic hepatitis, pechenochnokletochny excitement, the mixed defeat).

From skin: Quincke's disease, hematoma, small tortoiseshell, itch, rashes, nodozna nodular erythema.

From a musculoskeletal system and connecting fabric: an arthralgia, a mialgiya, including muscular spasms.

General frustration and local reactions: adynamy/fatigue, sensation of discomfort, hypostasis, fever.

In isolated cases during treatment montelukast of patients with asthma described developing of nasal bleeding, the syndrome of Charg-Strausa (SCS) (see the section "Features of Use").

Interaction with other medicines:

Astator it is possible to appoint 10 together with other drugs for prevention or prolonged treatment of asthma and treatment of allergic rhinitis. At a research of interaction between medicines the recommended clinical dose of montelukast had no considerable clinical influence on pharmacokinetics of such drugs: theophylline, Prednisonum, Prednisolonum, oral contraceptives (ethinylestradiol/norethindrone 35/1), терфенадин, digoxin and warfarin.

At patients who at the same time accepted phenobarbital the area under a curve "concentration time" (AUC) for montelukast decreased approximately by 40%. As montelukast is metabolized by the ZA4 RMS, it is necessary to be careful, especially concerning children if montelukast is appointed along with inductors RMS 3 A4, for example, Phenytoinum, phenobarbital and rifampicin.

The researches in vitro showed that montelukast is powerful CYP 2C8 inhibitor. However data of clinical trial of interaction of the medicines including montelukast and розиглитазон (drug is metabolized by means of CYP 2C8), showed that montelukast is not CYP 2C8 in vivo inhibitor. Thus, montelukast does not influence metabolism of drugs which are metabolized by means of this enzyme (for example a paklitaksel, a roziglitazon and a repagl_n_da).

Contraindications:

The increased individual sensitivity to drug components.

Overdose:

There is no special information on overdose treatment by drug.

At long-term researches of patients with chronic asthma montelukast was appointed in doses to 200 mg/days to adult patients for 22 weeks, and at short-term researches – to 900 mg/days for about one week, at the same time clinically significant side reactions were absent.

At post-marketing use and during clinical trials messages on acute overdose of drug, including administration of drug by adults and children in the doses exceeding 1000 mg arrived (about 61 mg/kg, the child at the age of the 42nd month). Received clinical and datas of laboratory corresponded to a safety profile for adult patients and children.

In most cases the overdose of any undesirable phenomena was not noted. Side effects which corresponded to a profile of safety of drug and included an abdominal pain, drowsiness, thirst, a headache, vomiting and a psychomotor hyperactivity were most often observed.

It is unknown, or montelukast by means of peritoneal dialysis or a hemodialysis is removed.

Treatment: symptomatic терапя.

Storage conditions:

To store in original packaging at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets at the blister; on 3 blisters at cardboard to packaging.