Glamont, 4 mg 28 pcs.

Indications

Prevention and long-term treatment of bronchial asthma in children aged 2 to 5 years (inclusive) for chewable tablets 4 mg and in children aged 6 to 14 years (inclusive) for chewable tablets 5 mg, including prevention of daytime and nighttime symptoms of the disease, treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid and prevention of bronchospasm caused by exercise load.
Relief of daytime and nighttime symptoms of seasonal and/or year-round allergic rhinitis in children aged 2 to 5 years (inclusive) for 4 mg chewable tablets and in children aged 6 to 14 years (inclusive) for 5 mg chewable tablets.

Pharmacological effect

Pharmacotherapeutic group: Anti-inflammatory antibronchoconstrictor agent – leukotriene receptor blocker.

ATX code: R03DC03

Pharmacological characteristics

Pharmacodynamics
Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are strong mediators of inflammation – eicosanoids, which are secreted by various cells, including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl-leukotriene receptors. Cysteinyl-leukotriene receptors type 1 (CysLT1 receptors) are present in the human respiratory tract (including bronchial smooth muscle cells, macrophages) and other inflammatory cells (including eosinophils and some
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 permeability
vessels and an increase in the number of eosinophils. In allergic rhinitis, after exposure to an allergen, cysteinyl leukotrienes are released from proinflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which is manifested by symptoms of allergic rhinitis. An intranasal test with cysteinyl leukotrienes showed an increase in the resistance of the nasal airways and symptoms of nasal obstruction.
Montelukast is a highly active drug when taken orally that significantly improves inflammation in bronchial asthma. According to biochemical and pharmacological analysis, montelukast binds with high affinity and selectivity to CysLT1 receptors, without interacting with other pharmacologically important receptors in the respiratory tract (such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiological effects of the cysteinyl leukotrienes LTC4, LTD4 and LTE4 by binding to CysLT1 receptors without stimulating these receptors.
Montelukast inhibits CysLT1 receptors in the airways, as demonstrated by its ability to block the development of bronchospasm in response to inhaled LTD4 in patients with asthma. A dose of 5 mg is sufficient to relieve bronchospasm induced by
LTD4.
Montelukast causes bronchodilation within 2 hours after oral administration and may enhance bronchodilation caused by β2-agonists.

Pharmacokinetics
Suction
After oral administration, montelukast is rapidly and almost completely absorbed. In adult patients, after taking 5 mg chewable tablets on an empty stomach, the maximum plasma concentration (Cmax) is achieved after 2 hours. The average bioavailability is 73%. After taking 4 mg chewable tablets on an empty stomach in patients aged 2 to 5 years, Cmax is achieved within 2 hours.

Distribution
The binding of montelukast to plasma proteins is more than 99%. The volume of distribution at steady state is on average 8-11 liters. Preclinical studies have shown minimal penetration of montelukast across the 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, the concentration of montelukast metabolites in the blood plasma at steady state in adults and children is not determined.
In vitro studies have shown that cytochrome P450 CYP isoenzymes (3A4, 2A6, 2C8 and 2C9) are involved in the metabolism of montelukast, while at therapeutic concentrations montelukast does not inhibit cytochrome P450 CYP isoenzymes: 3A4, 2C9, 1A2,
2A6, 2C19 and 2D6. Metabolites have little therapeutic effect of montelukast.

Removal
Plasma clearance of montelukast in healthy adult volunteers averages 45 ml/min. After oral administration of radiolabeled montelukast, 86% of its amount is excreted through the intestines within 5 days and less than 0.2% through the kidneys, confirming that montelukast and its metabolites are excreted almost exclusively in bile.
The half-life of montelukast in young healthy adults ranges from 2.7 to 5.5 hours. The pharmacokinetics of montelukast remains almost linear when administered orally at doses above 50 mg. When taking montelukast in the morning and evening hours
no differences in pharmacokinetics are observed. When taking 10 mg of montelukast 1 time per day, a moderate (about 14%) accumulation of the active substance in plasma is observed.

Features of the pharmacokinetics of montelukast in different groups of patients

Gender
The pharmacokinetics of montelukast are similar in men and women.

Elderly patients
With a single oral dose of 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in elderly and young patients. The plasma half-life of montelukast is slightly longer in older adults. Drug dose adjustments for
elderly people are not required.

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

Liver failure
In patients with mild to moderate hepatic impairment and clinical manifestations of cirrhosis, a slowdown in the metabolism of montelukast was observed, accompanied by an increase in the area under the concentration-time pharmacokinetic curve (AUC) by approximately 41% after a single dose of 10 mg.
The half-life of montelukast in these patients is slightly longer than in healthy volunteers (mean half-life 7.4 hours).
No dose adjustment of montelukast is required for patients with mild to moderate hepatic impairment. There are no data on the nature of the pharmacokinetics of montelukast in patients with severe liver failure (more than 9 points on the Child-Pugh scale).

Kidney failure
Since montelukast and its metabolites are practically not excreted through the kidneys, the pharmacokinetics of montelukast in patients with renal impairment have not been evaluated.
No dose adjustment is required for this group of patients.

Special instructions

The effectiveness of oral montelukast for the treatment of acute attacks of bronchial asthma has not been established, therefore montelukast tablets are not recommended for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always carry emergency medications for the treatment of acute asthma attacks (short-acting inhaled β2-agonists).
You should not stop taking montelukast during an exacerbation of bronchial asthma and the need to use emergency drugs to stop attacks (short-acting inhaled β2-agonists).
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, while improving respiratory function in patients with allergic bronchial asthma, nevertheless cannot completely prevent bronchoconstriction caused by NSAIDs.
The dose of inhaled glucocorticosteroids (GCS) used concomitantly with montelukast can be gradually reduced under medical supervision, but an abrupt replacement of inhaled or oral GCS with montelukast cannot be carried out.
There are reports of neuropsychiatric disorders in adults, adolescents and children taking montelukast. Post-marketing reports of montelukast include cases of agitation, aggressive behavior or hostility, anxiety, depression, confusion, impaired attention, sleep disturbances, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal behavior.
thinking and behavior (including suicide), tics and tremors. Clinical data from some post-marketing reports of montelukast are consistent with the pharmacological effect of the drug. Patients and doctors should be aware of the possibility of developing adverse reactions from the psyche and nervous system. If such changes occur, the patient should inform the attending physician. When
If such events occur, physicians should carefully evaluate the risks and benefits of continuing montelukast therapy.
In rare cases, patients receiving anti-asthma drugs, including leukotriene receptor antagonists, have experienced one or more of the following adverse events: eosinophilia, rash, worsening of pulmonary symptoms, cardiac complications and/or neuropathy, sometimes diagnosed as Churg-Strauss syndrome, systemic eosinophilic vasculitis. These cases were sometimes associated with
reducing the dose or discontinuing therapy with oral glucocorticosteroids. Although a causal relationship of these adverse events to leukotriene receptor antagonist therapy has not been established, caution should be exercised in patients taking montelukast. Appropriate clinical monitoring should be carried out in such patients.
When reducing the dose of systemic glucocorticosteroids in patients receiving montelukast, caution should be exercised and appropriate clinical monitoring should be carried out.
Glemont chewable tablets 4 mg and 5 mg contain aspartame, a source of phenylalanine. Patients with phenylketonuria should be informed about the content of aspartame. The drug Glemont chewable tablets 4 mg and 5 mg is not recommended for use in patients with phenylketonuria.

Use in elderly patients
There were no differences in the efficacy and safety profiles of the drug associated with the age of patients.

Impact on the ability to drive vehicles and machinery
There is no evidence that taking montelukast affects the ability to drive a car or operate machinery. However, when using the drug, side effects such as dizziness and drowsiness may occur.
In view of this, caution should be exercised when driving vehicles and performing actions that require rapid psychomotor reactions.

Active ingredient

Montelukast

Composition

1 chewable tablet 4 mg contains:

Active ingredient: montelukast sodium 4.2 mg, equivalent to montelukast 4.0 mg.
Excipients: mannitol 161.08 mg, microcrystalline cellulose 50.72 mg, croscarmellose sodium 7.20 mg, hyprolose (hydroxypropylcellulose) 7.20 mg, aspartame 1.20 mg, cherry flavor 3.60 mg, magnesium stearate 4.80 mg.

1 chewable tablet 5 mg contains:

Active ingredient: 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, hyprolose (hydroxypropylcellulose) 9.00 mg, aspartame
1.50 mg, cherry flavor 4.50 mg, magnesium stearate 6.00 mg.

Pregnancy

There have been no clinical studies of montelukast in pregnant women.
Montelukast should be used during pregnancy and breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus or child.
During post-registration use of the drug montelukast, the development of congenital limb defects was reported in newborns whose mothers took the drug montelukast during pregnancy. Most of these women also took other medications to treat asthma during pregnancy. A cause-and-effect relationship between taking montelukast and the development of congenital limb defects has not been established.
It is not known whether montelukast is excreted in breast milk. Since many drugs are excreted in breast milk, this must be taken into account when prescribing montelukast during breastfeeding.

Contraindications

Hypersensitivity to any of the components of the drug.
Children up to 2 years of age (for a dosage of 4 mg) and up to 6 years of age (for a dosage of 5 mg).
Phenylketonuria (contains aspartame).
With caution
Pregnancy, breastfeeding

Side Effects

According to the World Health Organization (WHO), adverse effects are classified according to their frequency as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000
up to <1/1000), very rarely (<1/10000); frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.
Infectious and parasitic diseases
very common: upper respiratory tract infections.
Immune system disorders
uncommon: hypersensitivity reaction, including anaphylaxis;
rare: angioedema;
very rare: eosinophilic infiltration of the liver.
Disorders of the skin and subcutaneous tissues
often: rash;
uncommon: tendency to form hematomas, urticaria, itching;
very rare: erythema nodosum, erythema multiforme.
Nervous system disorders
uncommon: headache, dizziness, drowsiness, paresthesia/hypoesthesia, convulsions.
Mental disorders
Uncommon: sleep disturbances (including nightmares), insomnia, somnambulism, irritability, restlessness, agitation (including aggressive behavior or hostility), psychomotor hyperactivity (including irritability, restlessness and
tremor), depression;
rarely: impaired attention, memory impairment;
very rare: hallucinations, disorientation, suicidal thoughts and suicidal behavior.
Cardiac disorders
rarely: palpitations.
Blood and lymphatic system disorders
rarely: increased tendency to bleed.
Gastrointestinal disorders
often: abdominal pain, diarrhea, nausea, vomiting, pancreatitis;
uncommon: dyspepsia, dry oral mucosa.
Disorders of the liver and biliary tract
often: increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood;
very rare: hepatitis (including cholestatic, hepatocellular and mixed liver lesions).
Musculoskeletal and connective tissue disorders
uncommon: arthralgia, myalgia, including muscle cramps.
Disorders of the respiratory system, chest and mediastinal organs
uncommon: nosebleeds;
very rare: pulmonary eosinophilia, Churg-Strauss syndrome.
General disorders and disorders at the injection site
often: pyrexia;
uncommon: asthenia/fatigue, malaise, edema.

The development of Churg-Strauss syndrome has been reported during treatment with montelukast (see section “Special Instructions”).

Experience of post-registration use of the drug
During the post-registration period of use of montelukast, the following adverse reactions were reported. Because these reactions have been reported spontaneously from a population of uncertain size, it is not always possible to reliably estimate
their frequency or determine the cause-and-effect relationship with the use of the drug.
Blood and lymphatic system disorders: tendency to increased bleeding, thrombocytopenia.
Immune system disorders: hypersensitivity reactions, including anaphylaxis, eosinophilic infiltration of the liver.
Mental disorders: agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, attention disorder, sleep disturbances, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism,
suicidal thinking and behavior (including suicide), tics and tremors.
Nervous system disorders: drowsiness, paresthesia/hypoesthesia, convulsions.
Cardiac disorders: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis, pulmonary eosinophilia.
Gastrointestinal disorders: diarrhea, dyspepsia, nausea, pancreatitis, vomiting.
Liver and biliary tract disorders: cases of cholestatic hepatitis, hepatocellular and mixed types of liver damage have been reported with the use of montelukast. Most of these side effects occurred in the presence of other
predisposing factors, such as taking concomitant medications, alcohol abuse, and the presence of other forms of hepatitis.
Skin and subcutaneous tissue disorders: angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticaria.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia, including muscle spasms.
Renal and urinary tract disorders: enuresis in children.
General disorders and disorders at the injection site: asthenia (increased fatigue)/fatigue, edema, pyrexia.
Patients with asthma receiving montelukast may develop systemic eosinophilia, sometimes accompanied by clinical signs of vasculitis consistent with Churg-Strauss syndrome, a condition often requiring systemic
glucocorticosteroid therapy. The development of these conditions is sometimes preceded by a reduction in doses of oral glucocorticosteroids. The doctor should be attentive to the appearance of symptoms in patients such as eosinophilia, hemorrhagic rashes,
worsening pulmonary symptoms, cardiac complications and/or neuropathy.

Interaction

Montelukast can be prescribed together with other drugs that are usually used for the prevention and long-term treatment of bronchial asthma and/or allergic rhinitis. The recommended therapeutic dose of montelukast did not have a clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethisterone 35/1), terfenadine, digoxin and warfarin.
The AUC value of montelukast is reduced by approximately 40% when taking phenobarbital simultaneously, which, however, does not require changes in the dose of montelukast.
In vitro studies have shown that montelukast inhibits the CYP2C8 isoenzyme.
However, in an in vivo drug interaction study between montelukast and rosiglitazone (metabolized with the participation of the CYP2C8 isoenzyme), there was no confirmation of inhibition of the CYP2C8 isoenzyme by montelukast, therefore, in clinical practice, the effect of montelukast on the CYP2C8-mediated metabolism of a number of drugs, including. paclitaxel, rosiglitazone, repaglinide, etc.
In vitro studies have shown that montelukast is a substrate of CYP2C8 and, to a lesser extent, isoenzymes CYP2C9 and 3A4. Data from a clinical drug interaction study of montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9) demonstrate that gemfibrozil increases the systemic exposure of montelukast by 4.4-fold. Coadministration of itraconazole, a strong CYP3A4 inhibitor, with gemfibrozil and montelukast did not result in an additional increase in the systemic exposure of montelukast. The effect of gemfibrozil on the systemic exposure of montelukast is not
may be considered clinically significant based on safety data when used at doses greater than the approved dose of 10 mg in adult patients (eg, 200 mg/day in adult patients for 22 weeks and up to 900 mg/day in patients taking the drug for approximately one week, no clinically significant adverse effects were observed). Thus, when co-administered with gemfibrozil, no dose adjustment of montelukast is required. Based on the results of in vitro studies, clinically significant drug interactions with other known CYP2C8 inhibitors (for example, trimethoprim) are not expected. In addition, concomitant use of montelukast with itraconazole alone did not significantly increase the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators
Montelukast is a reasonable addition to bronchodilator monotherapy if the latter do not provide adequate control of bronchial asthma. Once the therapeutic effect of treatment with montelukast is achieved, 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 treatment with inhaled corticosteroids. When stabilization of the patient’s condition is achieved, the dose of GCS may be reduced. The dose of GCS should be reduced gradually, under the supervision of a physician. In some cases, complete withdrawal of inhaled GCS is acceptable, but abrupt replacement of inhaled GCS with montelukast is not recommended.

Overdose

Symptoms. There are no data on symptoms of overdose when taking 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. There have been cases of acute overdose of montelukast (taking at least 1000 mg of the drug per day) in clinical practice and during clinical studies in adults and children. Clinical and laboratory data indicated comparable 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 safety profile of montelukast.

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

Storage conditions

In original packaging at a temperature not exceeding 25ºС.
Keep out of the reach of children.

Shelf life

2 years.
Do not use the drug after the expiration date.

Manufacturer

Glenmark Pharmaceuticals Ltd, India