Expiration date: 04/2025
Composition
1 chewable tablet contains:
active substance: 4.00 mg montelukast (montelukast sodium mg, 4,16);
auxiliary substances: mannitol 160,96 mg, cellulose microcrystalline 52,80 mg hyprolose 7,20 mg, croscarmellose sodium 7,20 mg, dye Pigment Blend PB-24880 (lactose monohydrate of 3.60 mg, dye iron oxide red 0.40 mg) of 4.00 mg magnesium stearate 2,40 mg, aspartame 1,20 mg, flavor cherry (Silarom Cherry Flavour 1219813182) 0.08 mg;
1 tablet, film-coated, contains:
active substance: 10.00 mg montelukast (montelukast sodium mg 10,40);
excipients: core - microcrystalline cellulose, type 102 89,30 mg hyprolose of 4.00 mg, croscarmellose sodium 6.00 mg lactose monohydrate 89,30 mg magnesium stearate 1.00 mg; film shell - Opadry II Beige 31F27012 (lactose monohydrate 1,440 mg, hypromellose 15cP 1,120 mg, titanium dioxide 1,011 mg, macrogol 4000 0.400 mg, dye iron oxide yellow 0,026 mg, dye iron oxide red of 0.003 mg) of 4.0 mg.
Pharmacological action
Cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are strong inflammatory eicosanoids, which are released from various cells including mast cells and eosinophils. These important mediators prostrations contact cysteinyl-leukotriene receptors (CysLT), present in the Airways and are responsible for the reaction of bronchospasm, mucus production, vascular permeability and the increase in the number of eosinophils.
Montelukast is active in oral administration a compound that has greater affinity and selectivity to the CysLT 1 receptors. Montelukast at a dose of less than 5 mg relieves the bronchospasm induced by inhalation of LTD4. Bronhodilatiruty effect is observed within 2 hours after oral administration. Bronhodilatiruty effect beta-agonists is enhanced when taking montelukast. Montelukast inhibits both early and late stage bronchospasm caused by exposure to antigens. Montelukast reduces the number of eosinophils in peripheral blood in adults and children, as well as significantly reduces the number of eosinophils in the Airways. In patients with hypersensitivity to acetylsalicylic acid receiving inhaled and/or oral glucocorticosteroid (GCS), adding montelukast to therapy provides better control of the disease.
Pharmacokinetics
Suction
After ingestion of montelukast rapidly and almost completely absorbed. Adult patients after administration of chewable tablets at a dose of 5 mg on an empty stomach, maximum concentration in plasma (Cmax) achieved within 2 hours. The mean value of bioavailability is 73%, this value decreases to 63% when taking montelukast with food. After taking the chewable tablets at a dose of 4 mg on an empty stomach in patients aged 2 to 5 years Cmax is achieved in 2 hours. The average value of one Hundred in this group of patients, 66% higher and the mean Cmin value below the same values in adults when taken tablets, film-coated, at a dose of 10 mg.
Distribution
The binding of montelukast with proteins of blood plasma is more than 99%. The volume of distribution at steady state, the average is 8 to 11 L. pre-clinical studies revealed minimal penetration montelukast using
blood-brain barrier. 24 hours after administration the concentration of montelukast is minimal in other tissues.
Metabolism
Montelukast is actively metabolized in the liver. When used in therapeutic doses, concentrations of metabolites of montelukast in plasma at steady state in adults and children is not determined.
In vitro studies showed that metabolism of montelukast involves cytochrome P450 isoenzymes (ZA4, 2A6 and 2C9), while in therapeutic concentrations of montelukast do not inhibit cytochrome P450 isoenzymes: ZA4, 2C9, 1A2, 2A6, 2C19 and 2D6. Metabolites have negligible therapeutic effect of montelukast.
Excretion
The half-life of montelukast in young healthy adult volunteers ranges from 2.7 to 5.5 h. Plasma clearance of montelukast in healthy adult volunteers averages 45 ml/min After oral administration of montelukast 86% of the total amount excreted via the gut in 5 days and less than 0.2% through the kidneys, along with data on its bioavailability confirms the excretion of montelukast and its metabolites mainly in the bile.
Pharmacokinetics in special cases
The pharmacokinetics of montelukast in women and men the same.
In elderly patients or patients with hepatic impairment mild and moderate severity is not required correction mode dosing montelukast. The pharmacokinetics of montelukast in patients with renal insufficiency has not been assessed. Because montelukast and its metabolites are not excreted by the kidneys, dose adjustment in this category of patients is not required. Data on the nature of the pharmacokinetics of montelukast in patients with severe violations of the liver (more 9 points on a scale child-Pugh) no.
When taking high doses of montelukast (20-and 60 times the recommended dose for adults), a decrease in the concentration of theophylline in plasma. When taking montelukast in the recommended dose of 10 mg 1 time per day, this effect is not observed.
Side effects
Infectious and parasitic diseases: infections of the upper respiratory tract. Violations by the blood and lymphatic system: increased tendency to bleeding, thrombocytopenia.
Special conditions
Mentalist the drug is not recommended for the treatment of acute asthma attacks. Patients with asthma are advised to always carry emergency medications. Upon the occurrence of an acute attack should be used inhalation beta-agonists short-acting. Patients must consult their doctor if they need more inhalations beta-agonists short-acting than usual.
Do not abruptly replace Metalast drug therapy inhaled or oral corticosteroids. There are no data proving the possibility of reducing the dose of oral GCS on the background of concomitant use of montelukast.
In rare cases, patients who receive antiastenicescoe medications, including montelukast, can develop systemic eosinophilia, sometimes accompanied by clinical signs of vasculitis syndrome called charge chrome—Strauss, a condition which eliminated through taking systemic corticosteroids. These cases are usually associated with a reduction of dose or termination of therapy with oral corticosteroids. It is impossible to exclude or to establish the probability that antagonists of leukotriene receptors may be associated with the development of the syndrome charge chrome—Strauss. Therefore, doctors need to warn of the possibility of eosinophilia, vascular rash, increased severity of pulmonary symptoms, cardiac complications, and/or neuropathy in patients. The patients that developed the symptoms mentioned above, you need to repeat the examination, and the scheme of their treatment to review. Drug treatment Mentalist does not prevent the development of bronchospasm in patients with hypersensitivity to acetylsalicylic acid to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.
The drug Mentalist contains aspartame, source of phenylalanine. This drug may cause harm to patients with phenylketonuria.
The drug contains lactose monohydrate and it should not be taken by patients with rare hereditary deseases: galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Effects on ability to drive vehicles and mechanisms
As a rule, montelukast does not affect the ability to drive vehicles or work with other mechanisms, but very rarely, some patients noted drowsiness and dizziness, the appearance of these symptoms, patients are not recommended to drive vehicles and do other activities that require concentration and speed of psychomotor reactions.
Testimony
Prophylaxis and chronic treatment of asthma in children, including:
—preventing daytime and nighttime symptoms (for children from 2 years and older);
—treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid (for children 6 years and older);
—prevention of bronchospasm, caused by physical strain (for children aged 2 years and older).
Relief of symptoms of seasonal and perennial allergic rhinitis in children from 2 years.
Contraindications
hypersensitivity to the active or any subsidiary of the drug substance;
—children up to age 2 years (for dosage 4 mg) and 6 years (for dosages of 5 mg);
—patients with rare hereditary diseases: galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
—phenylketonuria (contains aspartame).
USE DURING PREGNANCY AND BREASTFEEDING
The use of the drug Mentalist when pregnancy is possible if the expected benefit to the mother outweighs the potential risk to the fetus.
The decision on the abolition of breastfeeding on the period of application of the drug Mantelet is made on the basis of the evaluation of the intended benefits to the mother and the potential risk for the baby.
Drug interactions
In patients simultaneously treated with phenobarbital, area under the curve "concentration-time" montelukast decreased approximately 40%, however, dosage adjustment in these patients is not required. Since montelukast is metabolised by CYP3A4 should be used with caution, especially in children, if montelukast is used simultaneously with inducers of CYP3A4, such as phenytoin, phenobarbital and rifampicin. Montelukast can be administered together with other drugs, traditionally used for prevention and long-term treatment of asthma and/or allergic rhinitis. Montelukast in the recommended therapeutic dose had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethynodrel 35/1), terfenadine, digoxin and warfarin.
In vitro studies established that montelukast is a potent inhibitor of the CYP2C8 isoenzyme. However, in the study of drug interaction in vivo montelukast and rosiglitazona (a marker substrate representative of drugs primarily metabolized by isoenzyme CYP2C8) was not confirmed inhibition of the isoenzyme CYP2C8 montelukast. Thus, in clinical practice does not assume the effect of montelukast on CYP2PC8-mediated metabolism of several drugs, including paclitaxel, rosiglitazona, Repaglinide.
In vitro studies have shown that montelukast is a substrate of the isoenzyme CYP2C8, and to a lesser extent isozymes CYP2C9 and ZA4. Data from clinical studies of drug interactions in relation to montelukast and gemfibrozil (inhibitor of CYP2C8 as and 2C9) demonstrated that gemfibrozil increases the effect of systemic exposure of montelukast by 4.4 times. The co-administration of Itraconazole, a strong inhibitor of CYP3A4, with gemfibrozil and montelukast did not lead to further increase of the effect of systemic exposure of montelukast. The effect of gemfibrozil on the systemic exposure to montelukast can not be considered clinically significant based on safety data used in doses higher than approved dose of 10 mg for adult patients (for example, 200 mg/day to adult patients for 22 weeks and up to 900 mg/day for patients
taking the drug for approximately one week there were no clinically significant adverse effects). Thus, when co-administered with gemfibrozil dosage adjustment of montelukast is required. According to the results of in vitro studies, is not clinically significant drug-drug interactions with other known inhibitors of the isoenzyme CYP2C8 (e.g. trimethoprim). In addition, the co-administration of montelukast with Itraconazole alone did not lead to a significant increase in the effect of systemic exposure of montelukast. Combined treatment with bronchodilators
The drug Mentalist is a reasonable addition to monotherapy with bronchodilators, if the latter do not provide adequate control of asthma. Upon reaching the therapeutic effect of the drug treatment Mentalist you can start gradual reduction of the dose of bronchodilators. Combined treatment with inhaled corticosteroids
Drug treatment Metalast provides an additional therapeutic effect to the patients who use inhaled corticosteroids. Upon reaching stabilization of the condition, you can start gradual reduction of the dose of corticosteroids under the supervision of a physician. In some cases, permissible total abolition of inhaled corticosteroids, but the abrupt substitution with inhaled corticosteroids for the medication Mentalist is not recommended.
