Montel of the tab. chewing 4 mg No. 28

Pharmacological properties

Pharmacodynamics. tsisteinilleykotriyena (lc4, ltd4, lte4) are powerful eicosanoids of inflammation which are emitted with various cells, including corpulent and eosinophils. these important pro-asthmatic mediators contact tsisteinilleykotriyenovy receptors (cyslt) which are present at airways of the person (including myocytes of unstriated muscles and macrophages) and other cells of pro-inflammation (including eosinophils and some myeloid stem cells). cyslt are related to a pathophysiology oh and allergic rhinitis. at oh leykotriyenoposredovanny 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 mucous membrane of a nose during both phases (early and late) and shown by symptoms of allergic rhinitis. at intranasal test with cyslt the increase in resistance of pneumatic nasal ways and symptoms of nasal obstruction is shown.

Montelukast is active connection which with sharp selectivity and chemical affinity contacts CysLT ₁ - receptors. Montelukast causes considerable blocking of tsisteinilleykotriyenovy receptors of airways that is confirmed with its ability to inhibit the bronkhokonstriktion caused by inhalation of LTD ₄ , at patients with OH. Even the low dose of 5 mg causes considerable blockade of stimulated LTD ₄ bronkhokonstriktion. Montelukast causes a bronkhodilatation during 2 h after oral administration; this effect was additive to the bronkhodilatation caused by agonists of β-adrenoceptors.

Treatment by montelukast suppresses a bronchospasm both on early, and at a late stage, reducing reaction to antigens. Montelukast reduces quantity of eosinophils of peripheral blood at adults and children, considerably reduces quantity of eosinophils in airways (analysis of a phlegm) and improves clinical control OH.

Pharmacokinetics

Absorption. After reception, montelukast is quickly and almost completely soaked up. At adults at reception on an empty stomach of tablets, coated, in a dose of 10 mg of the C _max in blood plasma it is reached in 3 h. After reception on an empty stomach medicine in the form of chewable tablets in a dose of 5 mg of the C _max is reached in 2 h. The average bioavailability for chewable tablets is 73% and decreased up to 63% at reception with food. Average bioavailability for tablets, coated — 64%. Intake of usual food does not influence the C _max in blood plasma and bioavailability of tablets, coated.

Distribution. More than 99% of montelukast contact proteins of blood plasma. The volume of distribution of montelukast in a stationary phase averages 8–11 l. At a research of marked montelukast the passing through GEB was minimum. In all other fabrics of concentration marked the material radioisotope in 24 h after reception of a dose also was minimum.

Metabolism. Montelukast is actively metabolized. In researches with participation of the adults and children applying therapeutic doses of medicine, concentration of metabolites of montelukast in steady state of blood plasma are not defined.

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during the researches in vitro with use of microsomes of a liver of the person it is proved that P450 3A4, 2A6 and 2C9 cytochromes participate in montelukast metabolism. 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 P450 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6 cytochromes. Participation of metabolites in therapeutic effect of montelukast is minimum.

Removal. The clearance of montelukast in plasma of healthy adult volunteers averages 45 ml/min. After reception of an oral dose marked isotope of montelukast of 86% of medicine removes with a stake within 5 days also less than 0.2% — with urine. In total with bioavailability of montelukast at oral administration this fact specifies that its metabolites are almost completely removed with bile.

Pharmacokinetics in different groups of patients. For elderly people and also patients with a liver failure of easy and average extent of dose adjustment are not required. Patients with a heavy liver failure (9 points on Chayld's scale — I Drink) have no data on the nature of pharmacokinetics of montelukast.

Researches with participation of patients with a renal failure were not conducted by

. As montelukast and its metabolites are removed with bile, dose adjustment for patients with a renal failure is not considered necessary.

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At intake of montelukast in high doses (that in 20 and 60 times exceeded the dose recommended for adults) noted decrease in concentration of theophylline in blood plasma. This effect did not arise at reception of the recommended dose — 10 mg of 1 times a day.

Pharmacokinetic researches showed that profiles of concentration of chewable tablets of 4 mg at children at the age of 2–5 years are similar to a profile of concentration of coated tablets on 10 mg at adults, and tablets of 5 mg at children at the age of 6–14 years are similar to that of tablets, coated, in a dose of 10 mg at adults. Chewable tablets on 4 mg should be applied at children at the age of 2–5 years.

Indication

Tablet, film coated, 10 mg. additional treatment of easy and average degree persistent oh which is insufficiently controlled by inhalation corticosteroid medicines and also at insufficient clinical control of symptoms oh by means of agonists of the β-adrenoceptors of short-term action applied as necessary.

Symptomatic treatment of seasonal allergic rhinitis at patients OH.

OH Prevention which dominating component is the bronchospasm induced by physical activity.

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

Tablet for chewing of 5 mg (to children at the age of 6–14 years); tablets for chewing of 4 mg (to children at the age of 2–5 years):

• additional treatment persistent OH easy and the moderate severity which is insufficiently controlled by inhalation corticosteroid medicines and also at insufficient clinical control of symptoms OH by means of agonists of the β-adrenoceptors of short-term action applied as necessary;
• as an alternative to treatment by the inhalation corticosteroids applied in low doses at patients from easy degree persistent OH in which anamnesis were not the heavy attacks OH which demanded oral administration of corticosteroids and also recently for those patients at whom the intolerance of inhalation corticosteroid medicines is revealed;
• OH prevention which dominating component is the bronchospasm induced by physical activity;
• relief of symptoms of seasonal and year-round allergic rhinitis.

Use

Tablet, film coated, 10 mg use medicament orally, irrespective of meal.

to Adults and children 15 years for treatment OH are aged more senior than

or OH in combination with seasonal allergic rhinitis it is necessary to accept on 1 tablet (10 mg) of 1 times a day (evening).

For relief of symptoms of allergic rhinitis time of reception is selected individually.

General recommendations. The therapeutic effect of medicine concerning control OH occurs within 1 day. Patients should recommend to continue administration of medicament even at achievement of control OH and also during the periods of exacerbation of this pathology. It is not necessary to take the medicament together with the medicines containing montelukast.

patients of advanced age have

no need for dose adjustment, with renal failures or with abnormal liver functions of easy and moderate degree. There are no data on patients with a liver failure of heavy degree.

Dosage of medicine is identical to male and female patients.

Treatment by montelukast depending on other ways of treatment OH. Montel it is possible to appoint in addition to already existing course of treatment of the patient.

Inhalation corticosteroids. Montel it is possible to apply as additional therapy if inhalation corticosteroids in a combination with short-range β-agonists as means of first aid do not provide adequate clinical control of a disease.

Cannot replace inhalation corticosteroids with Montel sharply.

Tablet for chewing of 4 mg and 5 mg . Drug should be used at children under supervision of adults.

to Patients with OH and allergic rhinitis (seasonal and year-round) needs to take 1 chewable tablet of 4 mg or 5 mg of 1 times a day. For relief of symptoms of allergic rhinitis time of reception should be selected individually.

For treatment OH the dose for children at the age of 2–5 years makes 1 chewable tablet (4 mg) of 1 times a day in the evening, for 1 h to or in 2 h after meal. There is no need for dose adjustment for this age group. The medicament Montel in a dosage form chewable tablets of 4 mg is not recommended for children under 2 years.

In treatment OH the dose for children at the age of 6–14 years makes 1 chewable tablet (5 mg) of 1 times a day in the evening, for 1 to or through 2 after meal. There is no need for dose adjustment for this age group.

to Adults and children 15 years are aged more senior than

it is necessary to apply montelukast tablets on 10 mg.

Alternative to treatment by inhalation corticosteroids in low doses at easy degree persistent OH. Montelukast is not recommended as monotherapy at patients from average degree persistent OH. The decision on use of montelukast as alternatives to low doses of inhalation corticosteroids for children from easy degree persistent OH can be accepted only for patients at whom the heavy asthmatic attacks demanding reception of corticosteroids and also for patients who showed that they are incapable to apply inhalation corticosteroids are noted lately.

Persistent OH easy degree is defined by

as emergence of symptoms is OH more often than 1 time a week, but is more rare than 1 time a day, emergence of night symptoms is more often than 2 times a month, but normal function of lungs in the periods between episodes is more rare than 1 time a week.

If within 1 month of therapy by montelukast did not reach satisfactory control OH, it is necessary to estimate need of additional or other anti-inflammatory therapy, based on the step-by-step system of treatment OH. Patients need to be examined periodically for control assessment OH.

Preventive application before physical activities for prevention of an asthmatic attack. The bronchospasm caused by physical activities can be the main sign persistent OH that demands treatment by inhalation GKS. The condition of the patient should be estimated for the 2-4th week after an initiation of treatment montelukast. If the satisfactory treatment outcome is not revealed, it is necessary to make the decision on additional or other treatment.

Treatment by montelukast in connection with other ways of treatment OH. If treatment by montelukast is performed as additional therapy to inhalation corticosteroids, it is impossible to replace inhalation corticosteroids with montelukast sharply.

Contraindication

Hypersensitivity to montelukast or other components of medicine, children's age up to 15 years (for a dose of 10 mg).

Side effects

Blood and lymphatic system: tendency to strengthening of bleeding, thrombocytopenia.

Immune system: reactions of hypersensitivity, including anaphylaxis, eosinophilic infiltration of a liver. It was reported about isolated cases of the syndrome of Cherdzha — Stross (SCS) at patients with OH (see. Special INSTRUCTIONS).

Mental violations: a sleep disorder, including nightmares, insomnia, a sleep-walking, uneasiness, excitement (agitation), including agressive behavior or hostility, psychomotor hyperactivity (including irritability, concern, it is rare — a tremor), a depression; violation of attention, memory deterioration/loss; hallucinations, disorientation, suicide intentions and behavior (attempts of a suicide).

central nervous system: headache, slackness, dizziness, drowsiness, paresthesia/hypesthesia, convulsive attacks.

Cardiovascular system: heart consciousness (palpitation).

Respiratory system: nasal bleedings, pulmonary eosinophilia.

Digestive system: an abdominal pain, diarrhea, dryness in a mouth, thirst, dyspepsia, nausea, vomiting.

Gepatobiliarnaya system: increase in level of plasma Transaminases (AlAT, AsAT), hepatitis (including cholestatic, hepatocellular, damages of a liver of the mixed genesis).

Skin and hypodermic fabrics: rash, Quincke's disease, hematomas, urticaria, itch, knotty erythema, multiformny erythema.

Urinary system: enuresis at children.

Musculoskeletal system and connective tissue: arthralgia, myalgia, including muscular spasms.

Infection and invasion: upper respiratory tract infections.

General frustration: adynamy / increased fatigue, sensation of discomfort (indisposition), hypostases, pyrexia.

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In isolated cases during treatment by montelukast at patients OH described emergence of SChS.

Special instructions

Patients should warn that montet it is not necessary to apply to elimination of bad attacks of asthma. for elimination of attacks the treatment is recommended by the corresponding medicines. in case of a bad attack it is necessary to apply inhalation agonists of β-adrenoceptors of short action. it is necessary to consult with the doctor in case the patient needs the bigger number of inhalations by agonists of β-adrenoceptors of short action.

should not be replaced sharply with montelukast inhalation or oral corticosteroids. It is not necessary to take the medicament together with the medicines which are also containing montelukast.

do not have data which would prove that the dose of oral corticosteroid medicines can be reduced at a concomitant use of montelukast.

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It was reported about emergence of the psychoneurological phenomena at the patients accepting montelukast (see. Side EFFECTS). As can exist and other factors influencing these events it is unknown whether they have relationship of cause and effect using montelukast.

Doctors have to discuss a possibility of such events with the patients and/or their trustees. Patients and/or trustees should specify that they reported to the doctor about emergence psychoneurological change. In such cases it is necessary to revise risks and advantage of further medicament treatment.

In isolated cases at the patients receiving antiasthmatic means including montelukast, the system eosinophilia, sometimes together with clinical manifestations of a vasculitis — SChS (granulematozny allergic angiitis) which treatment is carried out by system corticosteroid medicines can be noted. Such cases usually, but not always, were connected with a dose decline or cancellation of corticosteroid medicines. It is impossible neither to disprove communication of antagonists of leukotriene receptors with development of SChS, nor to confirm therefore the doctor has to know about possibility at patients of an eosinophilia, vaskulitny rash, cardiovascular complications and/or neuropathy, deteriorations in pulmonary symptomatology. Patients at whom the above-stated symptoms developed need to undergo repeated inspection, and the scheme of their treatment should be revised.

At therapy by montelukast should not apply acetylsalicylic acid or other NPVP at patients from aspirinzavisimy OH. The medicament Montel, tablets, film coated, it is not necessary to apply at patients with rare hereditary diseases, intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption.

Montel Chewable tablets of 4 mg and 5 mg contain aspartame which is a phenylalanine source. Patients with phenylketonuria need to consider that each tablet of 4 mg contains phenylalanine in the quantity equivalent to a dose of phenylalanine of 0.674 mg; and each tablet of 5 mg contains phenylalanine in the quantity equivalent to a dose of phenylalanine of 0.842 mg.

Use during pregnancy and feeding by a breast. Researches on animals did not show an adverse effect on pregnancy or embryonic/fetal development.

Limited information on use of montelukast during pregnancy does not indicate

relationship of cause and effect between its application and emergence of malformation (such as congenital defects of extremities) about which it was seldom reported according to the global post-marketing experience of application. Montel it is possible to apply during pregnancy, only if it is considered necessary certainly.

Research on animals was shown that montelukast gets into breast milk. It is unknown whether montelukast gets into breast milk of women. Montel it is possible to apply during feeding by a breast, only if it is considered necessary certainly.

Children. The tablet medicament Montel, coated, 10 mg, appoint to adults and children 15 years are aged more senior. To children 15 years are aged younger it is necessary to use medicament in the form of chewable tablets. Chewable tablets on 4 mg apply at children at the age of 2–5 years, 5 mg — at children at the age of 6–14 years.

Ability to influence speed of response at control of vehicles or work with mechanisms. It is not expected that montelukast will affect ability of the patient to control of vehicles or other mechanisms. However in isolated cases there can be dizziness or drowsiness therefore during administration of medicament it is necessary to refrain from driving or other mechanisms.

Interaction

can appoint Montelukast by

together with other medicines for prevention or long-term treatment oh. the recommended clinical dose of montelukast has no considerable clinical influence on pharmacokinetics of such medicines: theophylline, Prednisonum, Prednisolonum, oral contraceptives (ethinylestradiol/norethindrone 35/1), terfenadin, digoxin and warfarin.

At the patients who are at the same time accepting phenobarbital, AUC for montelukast decreased approximately by 40%. It is necessary carefully (especially concerning children) to appoint montelukast along with inductors CYP 3A4, for example, Phenytoinum, phenobarbital and rifampicin as it is metabolized by CYP 3A4.

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In the researches in vitro it is shown that montelukast is powerful CYP inhibitor 2C8. However data of clinical trial of interaction of the medicines including montelukast and roziglitazon (medicine, metabolizirushchiysya by means of CYP 2C8), demonstrate that montelukast is not CYP inhibitor 2C8 in vivo. Thus, montelukast does not influence substantially metabolism of the medicines which are metabolized by means of CYP 2C8 (for example paklitakset, roziglitazon and repaglinid).

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during the researches in vitro it is established that montelukast is CYP substrate 2C8 and to a lesser extent 2S9 and ZA4. During clinical trial of interaction of montelukast and a gemfibrozil (CYP inhibitor 2C8 and 2C9) gemfibrozit increased system exposure of montelukast by 4.4 times. At simultaneous application with gemfibrozily or other powerful CYP inhibitors 2C8 of dose adjustment of montelukast it is not required, but the doctor has to consider the increased risk of emergence of side reactions.

by results of the researches in vitro clinically important interactions with less powerful CYP inhibitors 2C8 are not expected (for example with Trimethoprimum).

Simultaneous use of montelukast with itrakonazoly (powerful CYP inhibitor 3A4) did not lead

to significant increase in system exposure of montelukast.

Overdose

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during the long researches chronic oh montelukast was appointed in doses to 200 mg/days to adult patients, and in short-term researches — up to 900 mg/days during about 1 week, at the same time clinically significant side reactions did not arise.

Symptoms. It was reported about sharp overdose of montelukast. These cases concerned the adults and children accepting a dose over 1000 mg (the child has about 61 mg/kg of body weight at the age of 42 months). Adults and children had clinical and laboratory indicators within safety profile.

any undesirable phenomena are noted by

In the majority of messages about cases of overdose. There were more often side effects which answered a profile of safety of montelukast and included an abdominal pain, drowsiness, thirst, a headache, vomiting and psychomotor hyperactivity.

Treatment. There is no special information on treatment of overdose of montelukast. Symptomatic treatment. Antidote is absent. It is unknown whether montelukast by means of peritoneal dialysis or a hemodialysis is removed.

Storage conditions

In original packing at a temperature not above 25 °C.