Glemont - instructions for use, doses, side effects, contraindications

Excipients: mannitol 161.08 mg, microcrystalline cellulose 50.72 mg, croscarmellose sodium 7.20 mg, giprolose (hydroxypropyl cellulose) 7.20 mg, aspartame 1.20 mg, cherry flavoring 3.60 mg, magnesium stearate 4.80 mg.

1 tablet chewing 5 mg contains:

Active substance: Montelukast sodium 5.2 mg equivalent to montelukast 5.0 mg.

Excipients: mannitol 201.35 mg, microcrystalline cellulose 63.45 mg, croscarmellose sodium 9.00 mg, giprolose (hydroxypropylcellulose) 9.00 mg, aspartame 1.50 mg, cherry flavor 4.50 mg, magnesium stearate 6.00 mg.

Description:

Tablets 4 mg:

Oval, biconvex tablets from white to almost white with engraving "G"On one side and" 390 "on the other, with a characteristic smell.

Tablets 5 mg:

Round, biconcave tablets from white to almost white with an engraving "G"On one side and" 391 "on the other, with a characteristic smell.

Pharmacotherapeutic group:Anti-inflammatory anti-bronchoconstrictive agent - leukotriene receptor blocker

ATX: & nbsp

R.03.D.C.03 Montelukast

Pharmacodynamics:

Cysteinyl-leukotrienes (LTC₄, LTD₄, LTE₄) are strong inflammatory mediators - eicosanoids, which are excreted by different cells, including mast cells and eosinophils. These important proastmatic mediators are linked to cysteinyl-leukotriene receptors. Cysteinyl leukotriene 1-type receptors (CysLT₁- receptors) are present in the human respiratory tract (including bronchial smooth muscle cells, macrophages) and other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). Cysteinyl-leukotrienes correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, increased mucus secretion, increased vascular permeability, and an increase in the number of eosinophils.In case of allergic rhinitis after exposure to the allergen, cysteinyl leukotrienes are released from the proinflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which is manifested by the symptoms of allergic rhinitis. An intranasal test with cysteinyl leukotrienes demonstrated an increase in the resistance of the airway nasal passages and symptoms of nasal obstruction.

Montelukast - highly active when administered medication, which significantly improves the inflammation in bronchial asthma. According to biochemical and pharmacological analysis montelukast with high affinity and selectivity is associated with CysLT₁receptors without interacting with other pharmacologically important receptors in the airways (such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiological action of LTC cysteinyl leukotrienes₄, LTD₄ and LTE₄by binding to CysLT₁receptors, without exerting a stimulating effect on these receptors.

Montelukast inhibits CysLT₁-receptors in the respiratory tract, which is confirmed by the ability to block the development of bronchospasm in response to inhalation LTD₄ in patients with bronchial asthma. Doses of 5 mg are sufficient for arresting bronchospasm induced LTD₄.

Montelukast causes bronchodilation within 2 hours after ingestion and may supplement the bronchodilation caused by β₂-adrenomimetics.

Pharmacokinetics:

Suction

After oral administration montelukast quickly and almost completely absorbed. In adult patients, after taking chewable tablets at a dose of 5 mg on an empty stomach, the maximum concentration in the blood plasma (C_max) is achieved after 2 hours. The average bioavailability is 73%. After taking chewable tablets at a dose of 4 mg fasting in patients aged 2 to 5 years, C_max is achieved in 2 hours.

Distribution

The binding of montelukast to plasma proteins is more than 99%. The volume of distribution in the equilibrium state averages 8-11 liters. Preclinical studies have revealed minimal penetration of montelukast through the blood-brain barrier. After 24 hours after administration, the concentration of montelukast is also minimal in other tissues.

Metabolism

Montelukast is actively metabolized in the liver. When used in therapeutic doses, the concentration of metabolites of Montelukast in blood plasma in an equilibrium state in adults and children is not determined.

In vitro studies have shown that cytochrome P450 isoenzymes are involved in the metabolism of montelukast CYP (3A4, 2A6, 2C8 and 2C9), while in therapeutic concentrations montelukast Does not inhibit cytochrome P450 isoenzymes CYP: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6. Metabolites have a slight therapeutic effect of Montelukast.

Excretion

The plasma clearance of montelukast in healthy adult volunteers averages 45 ml / min. After ingestion of radioactively labeled montelukast, 86% of its quantity is excreted with feces for 5 days and less than 0.2% in urine, which confirms that montelukast and its metabolites are excreted almost exclusively with bile.

The half-life of montelukast in young healthy adults ranges from 2.7 to 5.5 hours.

The pharmacokinetics of montelukast retains a practically linear character when administered in doses over 50 mg.

When taking montelukast in the morning and evening hours, there is no difference in pharmacokinetics.

When 10 mg montelukast is administered 1 time a moderate (about 14%) cumulation of the active substance in the plasma is observed.

Peculiarities of pharmacokinetics of montelukast in different groups of patients

Floor

The pharmacokinetics of montelukast in men and women are similar.

Elderly patients

With a single oral administration of 10 mg montelukast, the pharmacokinetic profile and bioavailability are similar in elderly patients and young patients. The half-life of Montelukast from plasma is somewhat longer in older people. Correction of the dose of the drug in the elderly is not required.

Race

There were no differences in clinically significant pharmacokinetic effects in patients of different races.

Liver failure

In patients with hepatic insufficiency of mild and moderate severity and clinical manifestations of cirrhosis, a decrease in montelukast metabolism was noted, accompanied by an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) by approximately 41% after a single dose of 10 mg. The half-life of montelukast in these patients is slightly increased compared to healthy volunteers (mean half-life is 7.4 hours).

Changes in the dose of montelukast for patients with mild to moderate hepatic insufficiency are not required. There is no data on the character of the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale).

Renal insufficiency

Because the montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast in patients with renal insufficiency has not been evaluated. A dose adjustment for this group of patients is not required.

Indications:

Chewable tablets 4 mg

Prophylaxis and long-term treatment of bronchial asthma in children aged 2 to 5 years, including:

prevention of day and night symptoms of the disease;
relief of day and night symptoms of allergic rhinitis (seasonal and year-round).

Chewable tablets 5 mg

Prophylaxis and long-term treatment of bronchial asthma in children aged 6 to 14 years, including:

prevention of day and night symptoms of the disease;
treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid;
prevention of bronchospasm caused by physical exertion;

Cupping of day and night symptoms of seasonal and / or all-year-round allergic rhinitis in children aged 6 to 14 years.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Children under 2 years of age (for a dosage of 4 mg) and up to 6 years (for a dosage of 5 mg);

- phenylketonuria (contains aspartame).

Carefully:

Pregnancy, the period of breastfeeding.

Pregnancy and lactation:

Clinical studies of montelukast with the participation of pregnant women have not been conducted. Montelukast should be used during pregnancy and during breastfeeding only if the expected benefit to the mother exceeds the potential risk to the fetus or the baby.

It is not known whether montelukast with breast milk. Since many drugs are excreted in breast milk, this should be taken into account when appointing montelukast during breastfeeding.

Dosing and Administration:

The drug is taken orally once a day, regardless of food intake. The tablet can be swallowed whole or chewed before swallowing.

Admission of the drug by children is carried out under the supervision of adults.

Glemont should be taken 1 hour before or 2 hours after meals.

With bronchial asthma or bronchial asthma and allergic rhinitis:

For children aged 2 to 5 years - 1 tablet chewing in a dose of 4 mg once a day in the evening.

For children aged 6 to 14 years - 1 chewable tablet in a dose of 5 mg once a day in the evening.

With allergic rhinitis:

For children aged 2 to 5 years - 1 chewable tablet in a dose of 4 mg once a day and for children aged 6 to 14 years - 1 chewable tablet in a dose of 5 mg once a day in an individual mode, depending on the time of the most acute exacerbation of symptoms.

There is no need for dose adjustment within these age groups.

For treatment patients of other age groups a different dosage form is available and the dose of the drug - film-coated tablets, 10 mg.

General recommendations

The dose of the drug is the same for both female and male patients. The therapeutic effect of montelukast on the indicators reflecting the course of bronchial asthma develops during the first day. The patient should continue to take the drug, both during the control period for the symptoms of bronchial asthma, and during the exacerbation of bronchial asthma.

For elderly patients, patients from renal insufficiency, patients with mild and moderate liver function disorders, and also, depending on sex, no special dose selection is required.

There is no data on the use of montelukast in patients with severe impairment of liver function.

The appointment of montelukast concomitantly with other treatments for bronchial asthma

Montelukast can be added to the treatment of the patient with bronchodilators and inhaled glucocorticosteroids (GCS) (see section "Interaction with other drugs").

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (≥1/10), often (from ≥ 1/100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Infectious and parasitic diseases:

Often: infections of the upper respiratory tract.

From the immune system:

infrequently: hypersensitivity reaction, including anaphylaxis;

rarely: angioedema;

rarely: eosinophilic liver infiltration.

From the skin and subcutaneous tissue:

often: rash

infrequently: propensity to form a hematoma, hives, itching;

rarely: nodal erythema, erythema multiforme.

From the central nervous system:

infrequently: headache, dizziness, drowsiness, paresthesia / hypoesthesia, convulsions.

Mental disorders:

infrequently: sleep disturbances (including nightmares), insomnia, somnambulism, irritability, anxiety, agitation (including aggressive behavior or hostility), psychomotor hyperactivity (including irritability, anxiety and tremor), depression;

rarely: violation of attention, memory impairment;

rarely: hallucinations, disorientation, suicidal thoughts and suicidal behavior.

From the side of the cardiovascular system:

rarely: a feeling of palpitations.

On the part of the blood and lymphatic system:

rarely: increased tendency to bleeding.

From the gastrointestinal tract (GIT):

often: abdominal pain, diarrhea, nausea, vomiting, pancreatitis;

infrequently: dyspepsia, dryness of the oral mucosa.

From the liver and biliary tract:

often: increased activity of "hepatic" transaminases (alanine aminotransferase (ALT), aspartate aminotransferase, (ACT));

rarely: Hepatitis (including cholestatic, hepatocellular and mixed liver damage).

From the musculoskeletal and connective tissue:

infrequently: arthralgia, myalgia (including muscle cramps).

From the respiratory system:

infrequently: nasal bleeding;

rarely: Charge-Strauss syndrome, pulmonary eosinophilia.

Other:

often: hyperthermia;

infrequently: asthenia / fatigue, malaise, swelling.

During the treatment, montelukast reported the development of the Charge-Strauss syndrome (see section "Special instructions").

Overdose:

Symptoms

Data on symptoms of an overdose with montelukast in patients with bronchial asthma at a dose of up to 200 mg per day for 22 weeks and at a dose of 900 mg per day for one week was not revealed.

There have been cases of acute overdose with montelukast (intake of at least 1000 mg per day) in clinical practice and during clinical trials in adults and children. Clinical and laboratory data indicated the comparability of the safety profiles of Montelukast in children, adults and elderly patients.

The most common side effects were thirst, drowsiness, vomiting, psychomotor agitation, headache and abdominal pain. These side effects are consistent with the Montelukast safety profile.

Treatment

Treatment for acute overdose is symptomatic. There is no information on the specific treatment of the overdose of montelukast. There is no data on the effectiveness of peritoneal dialysis or hemodialysis.

Interaction:

Montelukast can be prescribed together with other medications that are commonly used for the prevention and long-term treatment of bronchial asthma and / or allergic rhinitis.

The recommended therapeutic dose of montelukast had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol / norethisterone 35/1), terfenadine, digoxin and warfarin.

Value AUC montelukast decreases with simultaneous reception of phenobarbital by about 40%, which, however, does not require a change in the dosage of montelukast.

In studies in vitro determined that montelukast inhibits isoenzyme CYP2C8.However, in the study of drug interactions in vivo Montelukast and rosiglitazone (metabolized with the participation of isoenzyme CYP2C8) there was no confirmation of the inhibition of isoenzyme by montelukast CYP2C8, therefore, in clinical practice, the effect of montelukast on СУР2С8-mediated metabolism of a number of medications is not expected, incl. paclitaxel, rosiglitazone, repaglinide, etc.

Research in vitro showed that montelukast is a substrate CYP2C8, and to a lesser extent isoenzymes CYP2C9 and 3A4. Data from the clinical trial of drug interaction for montelukast and gemfibrozil (an inhibitor of both CYP2C8, and 2C9) demonstrate that gemfibrozil increases the system exposure of Montelukast 4.4 times. The simultaneous administration of itraconazole, a potent inhibitor of CYP3A4, together with gemfibrozil and montelukast did not lead to an additional increase in the systemic exposure of montelukast. The effect of gemfibrozil on the systemic effect of montelukast can not be considered clinically significant on the basis of safety data when administered at doses exceeding the approved dose of 10 mg for adult patients (eg 200 mg / day for adult patients for 22 weeks and up to 900 mg / day for patients,taking a drug for about one week, there were no clinically significant negative effects). Thus, with a co-administration with gemfibrozilom correction of the dose of montelukast is not required. Based on research results in vitro no clinically significant drug interactions with other known inhibitors of CYP2C8 (for example, with trimethoprim) are expected. In addition, simultaneous administration of montelukast with itraconazole alone did not result in a significant increase in the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators

Montelukast is a well-founded addition to monotherapy with bronchodilators if the latter do not provide adequate control of bronchial asthma. After achieving the therapeutic effect of treatment with Montelukast, a gradual reduction in the dose of bronchodilators can be started.

Combined treatment with inhaled glucocorticosteroids (GCS).

Treatment with Montelukast provides an additional therapeutic effect to patients receiving inhaled glucocorticosteroids. At achievement of stabilization of a status of the patient reduction of a dose of GCS is possible.The dose of GCS should be reduced gradually, under the supervision of a doctor. In some cases, complete cancellation of inhaled glucocorticosteroids is permissible, but a sharp substitution of inhaled glucocorticosteroids for montelukast Not recommended.

Special instructions:

The effectiveness of montelukast for oral administration for the treatment of acute attacks of bronchial asthma is not established, therefore montelukast in tablets it is not recommended to prescribe for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always have emergency medications to stop acute attacks of bronchial asthma (inhaled β₂agonists of short action).

You should not stop taking montelukast during a period of exacerbation of asthma and the need for emergency drugs to stop attacks (inhaled β₂agonists of short action).

Patients with a confirmed allergy to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during treatment with montelukast, since montelukast, improving respiratory function in patients with allergic bronchial asthma, nevertheless, can not completely prevent the bronchoconstriction caused by their NSAIDs.

The dose of inhaled glucocorticosteroids (GCS), used in conjunction with montelukast, you can gradually reduce under supervision of a physician, but a sharp substitution of inhaled or oral corticosteroids montelukast should not be carried out.

In patients who took montelukast, psychoneurological disturbances have been described (see the "Side effect" section). Given that these symptoms could be caused by other factors, it is not known whether they are associated with taking montelukast. The physician should discuss these adverse events with patients and / or their parents / guardians. Patients and / or their parents / guardians should explain that in case of such symptoms it is necessary to inform the attending physician about it.

In rare cases, patients treated with anti-asthma drugs, including leukotriene receptor antagonists experienced one or more adverse effects of the following: eosinophilia, rash, worsening pulmonary symptoms, cardiac complications and / or neuropathy, sometimes diagnosed as Churg-Strauss syndrome, systemic eosinophilic vasculitis .These cases have sometimes been associated with a reduction in the dose or withdrawal of oral glucocorticosteroid therapy. Although the causal relationship of these adverse events with therapy with leukotriene receptor antagonists has not been established, patients receiving montelukast, care must be taken. In such patients, appropriate clinical observation is necessary.

With a decrease in the dose of systemic glucocorticosteroids in patients receiving montelukast, care must be taken and clinical monitoring performed.

The drug Glemont tablets chewing 4 mg and 5 mg contains aspartame - A source of phenylalanine. Patients with phenylketonuria should be informed of the content of aspartame. Drug Glemont tablets chewing 4 mg and 5 mg is not recommended for use in patients with phenylketonuria.

Application in elderly patients

Differences in the profiles of efficacy and safety of the drug, associated with the age of patients, have not been identified.

Effect on the ability to drive transp. cf. and fur:

Data indicating that the administration of montelukast affects the ability to drive a car or moving machinery has not been identified.However, when the drug is used, side effects such as dizziness and drowsiness may occur. In view of this, care must be taken when driving vehicles and performing actions requiring rapidity of psychomotor reactions.

Form release / dosage:

Chewable tablets, 4 mg and 5 mg.

Packaging:

For 28 tablets in a vial of high-density polyethylene with a lid with a first-opening control, containing one container of high-density polyethylene with 2 g of silica gel (desiccant).

One bottle in a cardboard box with instructions for use.

Storage conditions:

In a dry place, in the original package, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004042

Date of registration:27.12.2016

Expiration Date:27.12.2021

The owner of the registration certificate:Glenmark Pharmaceuticals Co., Ltd.Glenmark Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

GLENMARK PHARMACEUTICALS, Ltd. India

Representation: & nbspGLENMARK PHARMACEUTICALS LTD. GLENMARK PHARMACEUTICALS LTD. India

Information update date: & nbsp25.01.2017

Illustrated instructions

Instructions

Glemont (Glemont)