Lukast tab. of p/o of 10 mg No. 30

Pharmacological properties

Pharmacodynamics. tsisteinilleykotriyena (ltc4, ltd4, lte4) are powerful eicosanoids of inflammation which are released by various cells, including mast cells and eosinophils. these important pro-asthmatic mediators contact tsisteinilleykotriyenovy receptors (cyslt) which are present at airways of the person and cause such reaction as a bronchospasm and also hypersecretion, increase in permeability of vessels and increase in quantity of eosinophils. cyslt are related to a pathophysiology oh and allergic rhinitis. at oh leykotriyenoposredovanny effects include a bronchospasm, expectoration, change of permeability of vessels and increase in quantity of eosinophils. at allergic rhinitis after exposure with cyslt allergen are produced in a nasal mucous membrane during both phases (early and late) that is shown by symptoms of allergic rhinitis. at intranasal test with cyslt the increase in resistance of pneumatic nasal ways and symptoms of nasal obstruction were shown.

Montelukast is active connection which with sharp selectivity and chemical affinity contacts CysLT ₁ - receptors. Montelukast substantially blocks tsisteinilleykotriyenovy receptors of airways that is confirmed with its ability to inhibit a bronkhokonstriktion at patients with OH, LTD _{4 caused by inhalation} . Montelukast causes a bronkhodilatation during 2 h after oral administration; this effect was 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 quantity of eosinophils of peripheral blood at adult patients and children. In a separate research the intake of montelukast considerably reduced quantity of eosinophils in airways (on measurements of a phlegm).

Pharmacokinetics. Absorption. Montelukast after oral administration is absorbed quickly and almost completely. After use of medicine (a tablet of 10 mg, coated) by the C _{max adult on an empty stomach} in blood plasma it is reached in 3 h. The bioavailability at oral administration is 64%. Intake of usual food does not affect bioavailability and on the C _max at oral administration. Safety and efficiency of medicine are proved in clinical trials where tablets on 10 mg applied without meal time.

Distribution. More than 99% of montelukast contact proteins of blood plasma. The volume of distribution of montelukast in equilibrium state is 8–11 l. Researches at animals with application it is radioactive marked montelukast confirm the minimum extent of passing through GEB. Besides, concentration of radioactive material in 24 h after introduction were minimum in all other fabrics.

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

P450 2C8 Cytochrome is the main enzyme in montelukast metabolism. Besides, CYP cytochromes 3A4 and 2C9 are of little importance in montelukast metabolism though itrakonazol (CYP inhibitor 3A4) did not change pharmacokinetic indicators of montelukast at the healthy volunteers receiving 10 mg of montelukast a day. According to results of the researches in vitro with use of microsomes of a liver of the person, therapeutic plasma concentration of montelukast do 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 from blood plasma of healthy adult volunteers averages 45 ml/min. After reception marked by isotope of montelukast of 86% it is removed with a stake within 5 days and less than 0.2% — with urine. In total with bioavailability of montelukast at oral appointment this fact indicates 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 of dose adjustment is not required. 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 considered necessary. Patients with a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu) have no data on the nature of pharmacokinetics of montelukast.

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

Indication

Additional treatment oh at patients with persistent oh easy and moderate severity which is insufficiently controlled inhalation gks and also at insufficient clinical control oh by means of the β-agonists of short-term action applied if necessary. symptomatic treatment of seasonal allergic rhinitis at patients oh.

Prevention of the bronchospasm caused by physical activity.

Symptomatic treatment of seasonal and year-round rhinitis.

Dose for patients (aged from 15 years) with oh or with oh and the accompanying seasonal allergic rhinitis makes

10 mg (tablet) a day, in the evening. for reduction of expressiveness of symptoms of allergic rhinitis time of reception should be selected individually.

General recommendations. Therapeutic impact of the medicine Lukast on indicators of control of asthma occurs within 1 day. Drug can be used irrespective of meal. Patients should recommend to continue to take the medicament Lukast even if will reach control OH and also during the periods of its aggravation. Drug should not be used along with other means which contain the same active ingredient — montelukast.

does not have

need for dose adjustment for patients with a renal failure or a liver easy and moderate severity. There are no data on patients with a liver failure of heavy degree. A dosage for men and women identical.

Lukast Drug treatment depending on other treatment of asthma. Lukast it is possible to appoint in addition to already existing therapy of the patient.

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

cannot replace with Drug inhalation GKS sharply.

Contraindication

Hypersensitivity to medicine components.

Side effects

from nervous system: headache.

from a GIT: abdominal pain.

General violations: indisposition, thirst.

Side reactions registered during the post-marketing period

from blood and lymphatic system: tendency to strengthening of bleeding.

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

from mentality: the sleep disorder, including nightmares, hallucinations, insomnia, irritability, uneasiness, anger, impatience, excitement, including agressive behavior or hostility, psychomotor hyperactivity, a tremor, depressions, violation of attention, a memory impairment, a disorientation, is very rare — suicide intentions and behavior.

from nervous system: slackness and dizziness, paresthesia/hypesthesia, attacks.

from a cardiovascular system: heartbeat.

from a GIT: diarrhea, dryness in a mouth, dyspepsia, nausea, vomiting.

from a gepatobiliarny system: increase in level of Transaminases in blood plasma (AlAT, AsAT), hepatitis (cholestatic, hepatocellular and the mixed damages of a liver).

from kidneys and urinary tract: enuresis at children.

from skin and hypodermic fabrics: Quincke's disease, hematoma, small tortoiseshell, itch, rash, knotty erythema, multiformny erythema.

from a musculoskeletal system and connective tissue: arthralgia, myalgia, including muscular spasms.

General violations and local reactions: adynamy / increased fatigue, sensation of discomfort, hypostasis, fever. In rare instances at treatment montelukast of patients OH described developing of nasal bleeding, a syndrome of Cherdzha — Strossa (see. Special INSTRUCTIONS).

Special instructions

As medicament as excipient contains dye e110, it is necessary to consider that it can cause allergic reactions.

Patients should warn that Lukast should not apply to elimination of bad attacks OH and also that patients have to have always at themselves the corresponding medicine of the emergency help. In case of a bad attack it is necessary to apply inhalation β-agonists of short action. Patients have to consult as soon as possible with the doctor if it is necessary for them bigger, than usually, the number of inhalations of β-agonists of short action.

should not replace therapy with montelukast with inhalation or oral GKS sharply. There are no data demonstrating that the dose of oral GKS can be lowered at simultaneous use of montelukast.

It was reported about emergence of the psychoneurological phenomena at the patients accepting montelukast (see. Side EFFECTS). As other factors can influence these phenomena, it is unknown whether these phenomena using montelukast are connected. Doctors have to discuss these undesirable phenomena with the patients. Patients need to report to the doctor about emergence of such changes.

In rare instances at the patients receiving antiasthmatic means including montelukast, the system eosinophilia, sometimes together with clinical manifestations of a vasculitis, a so-called syndrome of Cherdzha — Stross whose treatment is carried out by means of system corticosteroids can develop. Such cases usually (but not always) were connected with a dose decline or cancellation of GKS. Probability that antagonists of leukotriene receptors can be connected with emergence of a syndrome of Cherdzha — Stross cannot be disproved or confirmed. Doctors have to remember possibility at patients of an eosinophilia, vaskulitny rash, increase in expressiveness of pulmonary symptomatology, complications from heart and/or neuropathy. Patients who had above-stated symptoms have to undergo repeated inspection, and the scheme of treatment should be revised.

Treatment by montelukast does not allow patients to apply acetylsalicylic acid or other NPVP with aspirinovy asthma.

to Patients with rare hereditary diseases, such as intolerance of a galactose, deficiency Lappa lactases or malabsorption of glucose galactose, it is not necessary to use this drug.

If at the patient established intolerance of some sugars, he should consult with the doctor before taking this drug.

Use during pregnancy and feeding by a breast

Pregnancy. During pregnancy it is only possible to appoint medicine when the expected advantage for mother exceeds potential risk for a fruit. According to international marketing experience, at children whose mothers accepted Lukast during pregnancy occasionally noted congenital defects of extremities. Most of these women accepted as well other medicines for treatment OH. The causal relationship between use of the medicine Lukast and emergence of malformation (congenital defects of extremities) is not proved.

Feeding by a breast. It is unknown whether montelukast gets into breast milk.

Lukast with care during feeding by a breast, considering a ratio risk/advantage.

Children. In this dosage form to apply at children aged 15 years are more senior. At children aged up to 15 years it is necessary to apply montelukast in the form of chewable tablets.

Ability to influence speed of response at control of vehicles or other mechanisms. Lukast in general does not affect ability to steer vehicles or other mechanisms. But it is necessary to consider the probability of such side effects from central nervous system as dizziness and drowsiness.

Interaction

along with other medicaments which are used usually for prevention or long-term treatment oh. the recommended clinical dose of montelukast has no considerable clinical impact on pharmacokinetics of such medicines as theophylline, Prednisonum, Prednisolonum, oral contraceptives (ethinylestradiol/norethindrone 35/1), terfenadin, digoxin and warfarin.

At patients who at the same time accepted phenobarbital AUC for montelukast decreased approximately by 40%. As montelukast is metabolized by CYP 3A4, 2C8, and 2C9, it is necessary to be careful, especially concerning children if to accept montelukast along with inductors CYP 3A4, 2C8, and 2C9, such as Phenytoinum, phenobarbital and rifampicin.

Research in vitro was shown that montelukast is powerful CYP inhibitor 2C8. However clinical trials of interaction of the medicines including montelukast and roziglitazon (the medicine which is metabolized by means of CYP 2C8), showed 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 a paklitaksela, a roziglitazona and a repaglinida).

during the researches in vitro it is established that montelukast is CYP substrate 2C8 and to a lesser extent 2C9 and 3A4. During clinical trial of interaction of medicines using montelukast and a gemfibrozil (CYP inhibitor 2C8 and 2S9) the last 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 the emergence of clinically important interactions with less powerful CYP inhibitors 2C8 is not expected (for example with Trimethoprimum). Simultaneous use of montelukast with less powerful CYP inhibitors 3A4 did not lead to significant increase in system exposure of montelukast.

is present

No special information on medicine overdose treatment lukast. at long researches of patients with chronic oh montelukast was appointed in doses to 200 mg/days to adult patients during 22 weeks, and at short-term researches — up to 900 mg/days during about 1 week, at the same time clinically important side reactions did not arise.

during post-marketing application and in clinical trials messages about sharp overdose of the medicine Lukast arrived. It concerned administration of medicament by adults and children in the doses exceeding 1000 mg (about 61 mg/kg, the child at the age of 42 months). Received clinical and datas of laboratory corresponded to safety profile for adults and children.

In the majority of messages about cases of overdose of the undesirable phenomena it is noted p. Most often revealed side effects which corresponded to a profile of safety of the medicine Lukast, including an abdominal pain, drowsiness, thirst, a headache, vomiting and psychomotor hyperactivity.

Does not know to

whether montelukast by means of peritoneal dialysis or a hemodialysis is removed. Symptomatic treatment.

Storage conditions

At a temperature not above 30 °C.