Glamont, 4 mg 28 pcs.

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

ATC code: R03DC03

Pharmacological characteristics

Pharmacodynamics
. Cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are strong inflammatory mediators, eicosanoids, that are secreted by various cells, including mast cells and eosinophils. These important proasthmatic mediators bind to cysteinyl-leukotriene receptors. Cysteinyl-leukotriene type 1 receptors (CysLT1 receptors) are present in human airways (including bronchial smooth muscle cells, macrophages) and other proinflammatory 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 vascular permeability
and increased eosinophil counts. In allergic rhinitis, after allergen exposure, cysteinyl leukotrienes are released from pro-inflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which manifests as symptoms of allergic rhinitis. An intranasal test with cysteinyl-leukotrienes demonstrated increased nasal airway resistance and symptoms of nasal obstruction.
Montelukast is a highly active oral medication that significantly improves inflammation scores 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 airways (such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiologic action of cysteinyl leukotrienes LTC4, LTD4, and LTE4 by binding to CysLT1 receptors without having a stimulatory effect on these receptors.
Montelukast inhibits CysLT1 receptors in the airways, as evidenced by its ability to block the development of bronchospasm in response to inhaled LTD4 in patients with bronchial asthma. A dose of 5 mg is sufficient to relieve bronchospasm induced by
LTD4.
Montelukast causes bronchodilation within 2 hours of oral administration and may enhance bronchodilation induced by β2-adrenomimetics.

Pharmacokinetics
Assimilation
Montelukast is rapidly and almost completely absorbed after oral administration. In adult patients, after ingestion of chewable tablets at a dose of 5 mg on an empty stomach, the maximum plasma concentration (Cmax) is reached after 2 hours. The average value of bioavailability is 73%. After chewable tablets in a dose of 4 mg on an empty stomach in patients aged 2 to 5 years Cmax is reached in 2 hours.

Distribution
Binding of montelukast to plasma proteins is more than 99%. The volume of distribution at equilibrium averages 8-11 liters. Preclinical studies have shown minimal penetration of montelukast through the blood-brain barrier. Twenty-four hours after administration, the concentration of montelukast is minimal in other tissues as well.

Metabolism
Montelukast is actively metabolized in the liver. When used in therapeutic doses, plasma concentrations of metabolites of montelukast are not determined in equilibrium in adults and children.
In vitro studies have shown that cytochrome P450 CYP isoenzymes (3A4, 2A6, 2C8 and 2C9) are involved in the metabolism of montelukast, while in therapeutic concentrations montelukast does not inhibit cytochrome P450 CYP isoenzymes: 3A4, 2C9, 1A2,
2A6, 2C19 and 2D6. Metabolites have insignificant therapeutic effect of montelukast.

Elimation
Plasma clearance of montelukast in healthy adult volunteers averages 45 ml/min. After ingestion of radioactively labeled montelukast, 86% of it is excreted through the intestine within 5 days and less than 0.2% through the kidneys, confirming that montelukast and its metabolites are excreted almost exclusively with bile.
The half-life of montelukast in young healthy adults is 2.7 to 5.5 hours. Pharmacokinetics of montelukast remains almost linear when administered orally in doses over 50 mg. When taking montelukast in the morning and evening hours
no differences in pharmacokinetics are observed. When taking 10 mg of montelukast once a day a moderate (about 14%) cumulation of the active substance in plasma is observed.

Peculiarities of the pharmacokinetics of montelukast in different groups of patients

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

Elderly patients
With a single oral administration of 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in elderly and younger patients. The plasma elimination half-life of montelukast is somewhat longer in the elderly. Dose adjustment of the drug in
elderly people is not required.

Race
No differences in clinically significant pharmacokinetic effects were found in patients of different races.

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

Renal insufficiency
Since montelukast and its metabolites are virtually not excreted through the kidneys, the pharmacokinetics of montelukast in patients with renal insufficiency have not been evaluated.
Adjustment of the drug dose for this group of patients is not required.

Prescribing montelukast concomitantly with other bronchial asthma treatment Montelukast can be added to patient treatment with bronchodilators and inhaled glucocorticosteroids (GCS) (see Montelust can be added to a patient’s treatment with bronchodilators and inhaled glucocorticosteroids (see Interaction with other medicines).

Interaction

Montelukast may be administered together with other drugs 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 (ethinylestradiol/norethisterone 35/1), terfenadine, digoxin and warfarin.
The AUC value of montelukast is decreased with concomitant administration of phenobarbital by about 40%, which, however, does not require changes in the dose of montelukast.
In in vitro studies it was found that montelukast inhibits CYP2C8 isoenzyme.
However, in in vivo drug interaction studies of montelukast and rosiglitazone (metabolized with participation of CYP2C8 isoenzyme) there was no confirmation of inhibition of CYP2C8 isoenzyme by montelukast, therefore in clinical practice no effect of montelukast on CYP2C8-mediated metabolism of several drugs, including
In vitro studies have shown that Montelukast is a substrate of CYP2C8 and, to a lesser extent, CYP2C9 and 3A4 isoenzymes. The data of clinical study of drug interaction in relation to Montelukast and gemfibrozil (inhibitor of both CYP2C8, and 2C9) shows that gemfibrozil increases systemic exposure of Montelukast 4.4 times. Co-administration of itraconazole, a potent CYP3A4 inhibitor, together with gemfibrozil and montelukast did not result in an additional increase in systemic exposure to montelukast. The effect of gemfibrozil on the systemic exposure of montelukast
cannot be considered clinically significant based on safety data when used at doses greater than the approved dose of 10 mg for adult patients (e.g., 200 mg/day for adult patients for 22 weeks and up to 900 mg/day for patients taking the drug for approximately one week, no clinically significant adverse effects were observed). Thus, no dose adjustment of montelukast is required when coadministered with gemfibrozil. According to the results of in vitro studies, no clinically significant drug interactions with other known CYP2C8 inhibitors (e.g., trimethoprim) are expected. In addition, concomitant administration of montelukast with itraconazole alone did not lead to a significant increase in the effect of systemic effects of montelukast.

Combined treatment with bronchodilators
Montelukast is a reasonable adjunct to monotherapy with bronchodilators if the latter do not adequately control bronchial asthma. Once the therapeutic effect of montelukast treatment has been achieved, a gradual reduction in the dose of bronchodilators may be initiated.

Combined treatment with inhaled glucocorticosteroids (GCS)Treatment with montelukast provides additional therapeutic benefit to patients treated with inhaled GCS. When the patient’s condition is stabilized, 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 abolition of inhaled GCS is acceptable, but abrupt replacement of inhaled GCS with montelukast is not recommended.

Special Instructions

Efficacy of oral montelukast for the treatment of acute attacks of bronchial asthma has not been established, so montelukast tablets are not recommended for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always carry emergency drugs for acute attacks of bronchial asthma (short-acting inhaled β2-agonists).
Montelukast should not be stopped during exacerbation of bronchial asthma and the need to use emergency drugs for arresting attacks (short-acting inhaled β2-agonists).
Patients with a confirmed allergy to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during treatment with montelukast because montelukast, while improving respiratory function in allergic bronchial asthma patients, 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 abrupt replacement of inhaled or oral GCS with montelukast should not be performed.
There are reports of neuropsychiatric disorders in adults, adolescents and children who have taken montelukast. Post-registration reports of montelukast use mention cases of agitation, aggressive behavior or hostility, anxiety, depression, disorientation, attention disorders, sleep disturbances, hallucinations, insomnia, irritability, memory disturbances, anxiety, somnambulism, suicidal
thinking and behavior (including suicide), tics and tremors. Clinical data from some post-registration reports on the use of montelukast are consistent with the pharmacological effects of the drug. Patients and physicians should be aware of the possibility of adverse mental and nervous system reactions. If such changes occur, the patient should inform the treating physician. If
such phenomena occur, physicians should carefully evaluate the risks and benefits of continuing therapy with montelukast.
In rare cases, patients receiving anti-asthmatic 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 have sometimes been associated with
dose reduction or withdrawal of oral glucocorticosteroid therapy. Although a causal relationship between these adverse events and therapy with leukotriene receptor antagonists has not been established, caution should be exercised in patients taking montelukast. Appropriate clinical monitoring should be performed in such patients.
Caution should be exercised and appropriate clinical monitoring should be performed in patients receiving montelukast when reducing the dose of systemic glucocorticosteroids.
Glemont chewable tablets 4 mg and 5 mg contain aspartame, a source of phenylalanine. Patients with phenylketonuria should be informed about the aspartame content. Glemont Chewable 4 mg and 5 mg tablets are not recommended for use in patients with phenylketonuria.

Application in elderly patients
No differences in the age-related efficacy and safety profiles of the drug were found.

Influence on ability to drive and operate vehicles
No data have been found to indicate that administration of montelukast affects the ability to drive or operate moving mechanisms. However, side effects such as dizziness and somnolence may occur when using the drug.
In view of this, caution should be exercised when driving motor transport and performing activities requiring rapid psychomotor reactions.

Synopsis

Tablets 4 mg:
Oval biconvex tablets from white to almost white with “G” engraved on one side and “390” on the other, with a characteristic odor.

Tablets 5 mg:
Round biconvex tablets from white to almost white with “G” engraved on one side and “391” on the other, with a characteristic odor.

Contraindications

• High sensitivity to any of the ingredients.
• Children under 2 years of age (for 4 mg dosage) and under 6 years of age (for 5 mg dosage).
• Phenylketonuria (contains aspartame).

Cautions
Pregnancy, breastfeeding
.

Side effects

According to the World Health Organization (WHO), adverse effects are classified according to their frequency of development as follows: Very common (≥1/10), common (≥1/100 to < 1/10), infrequent (≥1/1000 to < 1/100), rare (≥1/10000
to < 1/1000), very rare (< 1/10000); frequency unknown – the incidence could not be determined from available data.
Infectious and parasitic diseases
very common: upper respiratory tract infections.
Immune system disorders
infrequent: hypersensitivity reactions, including anaphylaxis;
rare: angioedema;
very rare: eosinophilic liver infiltration.
Skin and subcutaneous tissue disorders
often: rash;
infrequent: tendency to form hematomas, urticaria, itching;
very rare: erythema multiforme.
Nervous system disorders
infrequent: headache, dizziness, somnolence, paresthesia/hypoesthesia, seizures.
Mental disorders
infrequent: Sleep disturbances (including nightmares), insomnia, somnambulism, irritability, restlessness, agitation (including aggressive behavior or hostility), psychomotor hyperactivity (including irritability, restlessness and
tremor), depression;
rare: Attention disorder, memory impairment;
very rarely: hallucinations, disorientation, suicidal thoughts and suicidal behavior.
Chronic disorders
rarely: palpitations.
Blood and lymphatic system disorders
rarely: increased tendency to bleeding.
Gastrointestinal tract disorders
often: abdominal pain, diarrhea, nausea, vomiting, pancreatitis;
infrequent: dyspepsia, dry oral mucosa.
Hepatic and biliary tract disorders
often: increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in blood;
very rarely: hepatitis (including cholestatic, hepatocellular and mixed liver disease).
Muscular and connective tissue disorders
infrequent: arthralgia, myalgia, including muscle cramps.
Disorders of the respiratory system, thorax and mediastinum
infrequent: nasal bleeding;
very rare: pulmonary eosinophilia, Churg-Strauss syndrome.
General disorders and disorders at the injection site
often: pyrexia;
infrequent: asthenia/increased fatigue, malaise, edema.

During treatment with Montelukast, development of Churg-Strauss syndrome has been reported (see “Special Indications.

Post-registration experience with the drug
The following adverse reactions have been reported during the post-registration period of montelukast. Because these reactions were reported spontaneously from a population of uncertain size, it is not always possible to reliably estimate
their frequency or determine a causal relationship to the use of the drug.
Blood and lymphatic system disorders: tendency to increased bleeding, thrombocytopenia.
Disorders of the immune system: Hypersensitivity reactions, including anaphylaxis, eosinophilic infiltration of the liver.
Mental disorders: agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, disorientation, attention disorders, sleep disorders, hallucinations, insomnia, irritability, memory disorders, anxiety, somnambulism,
suicidal thinking and behavior (including suicide), tics and tremors.
Nervous system disorders:drowsiness, paresthesia/hypoesthesia, seizures.
Chronic disorders: heart palpitations.
Respiratory system, chest and mediastinal organs: nasal bleeding, pulmonary eosinophilia.
Gastrointestinal tract disorders: diarrhea, dyspepsia, nausea, pancreatitis, vomiting.
Hepatic and biliary tract disorders:Cases of cholestatic hepatitis, hepatocellular and mixed types of liver damage have been reported when using montelukast. Most of these side effects developed in the presence of other
predisposing factors, such as taking concomitant medications, alcohol abuse, and the presence of other forms of hepatitis.
Dermal and subcutaneous tissue disorders: Angioneurotic edema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticaria.
Muscular and connective tissue disorders: Arthralgia, myalgia including muscle spasms.
River and urinary tract disorders: enuresis in children.
General disorders and disorders at the site of administration: Asthenia (increased fatigue)/fatigue, edema, pyrexia.
In patients with bronchial asthma receiving montelukast, systemic eosinophilia may develop, 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 decrease in doses of oral glucocorticosteroids. The physician should pay careful attention to the appearance of symptoms such as eosinophilia, hemorrhagic rashes,
worsening of pulmonary symptoms, cardiac complications and/or neuropathy in patients.

Overdose

Symptoms. Data on overdose symptoms when receiving 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 have not been identified. 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 trials in adults and children. Clinical and laboratory data demonstrated 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. The treatment in acute overdose is symptomatic. There is no information about specific treatment of montelukast overdose. There is no data on the effectiveness of peritoneal dialysis or hemodialysis.

Pregnancy use

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

Similarities

Singular, Montelar, Montelukast, Singlon, Montelukast, Almont, Glémont