Asmont

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASmont (ASmont)

Composition:

Active ingredient: sodium montelukast;

1 tablet contains sodium montelukast 4.2 mg, equivalent to 4 mg of montelukast;

Excipients: mannitol (E 421), sodium croscarmellose, aspartame (E 951), cherry flavor, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, iron oxide red (E 172), magnesium stearate.

Pharmaceutical form. Chewable tablets.

Main physicochemical characteristics: pink-colored, flat cylindrical tablets with beveled edges*. The tablet surface has an imprint "4" on one side and is smooth on the other.

*Speckles may occur due to the manufacturing process.

Pharmacotherapeutic group. Systemic agents for obstructive respiratory diseases. Leukotriene receptor antagonists. ATC code R03DC03.

Pharmacological Properties

Pharmacodynamics

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released by various cells, including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl leukotriene receptors (CysLT) located in human airways and cause responses such as bronchoconstriction, mucus secretion, vascular permeability, and increased eosinophil counts.

Montelukast is an active compound that binds with high selectivity and chemical affinity to CysLT1 receptors. Montelukast produces significant blockade of cysteinyl leukotriene receptors in the airways, as confirmed by its ability to inhibit LTD4-induced bronchoconstriction in patients with asthma. Even a low dose of 5 mg results in significant inhibition of LTD4-stimulated bronchoconstriction. Montelukast induces bronchodilation within 2 hours of oral administration; this effect is additive to the bronchodilation caused by β-agonists.

Treatment with montelukast suppresses both early- and late-phase bronchoconstriction, reducing the response to antigens. Montelukast reduces the number of eosinophils in peripheral blood in adult and pediatric patients, significantly decreases the number of eosinophils in the airways (sputum analysis), and improves clinical asthma control.

Pharmacokinetics

Absorption

After administration, montelukast is rapidly and almost completely absorbed. Following a 4 mg chewable tablet dose given on an empty stomach to children aged 2 to 5 years, Cmax is reached within 2 hours after dosing. The mean oral bioavailability is 73% and decreases to 63% when taken with food. The mean Cmax is 66% higher, and the mean Cmin is lower than in adults after administration of 10 mg tablets.

Distribution

Over 99% of montelukast is bound to plasma proteins. The volume of distribution at steady state averages between 8 and 11 liters. In studies using radiolabeled montelukast, penetration across the blood-brain barrier was minimal. In all other tissues, concentrations of radiolabeled material 24 hours after dose administration were also minimal.

Metabolism

Montelukast is extensively metabolized. In studies using therapeutic doses, metabolite concentrations of montelukast in plasma at steady state were not detectable in adults or pediatric patients.

In vitro studies using human liver microsomes have shown that cytochrome P450 enzymes 3A4, 2A6, and 2C9 are involved in the metabolism of montelukast. At therapeutic concentrations, montelukast does not inhibit these cytochrome enzymes. The contribution of metabolites to the therapeutic effect of montelukast is considered minimal.

Excretion

Plasma clearance of montelukast in healthy adult volunteers averages 45 mL/min. After an oral dose of radiolabeled montelukast, 86% is excreted in feces within 5 days and less than 0.2% in urine. Combined with the oral bioavailability of montelukast, this indicates that its metabolites are almost exclusively eliminated via bile.

Pharmacokinetics in Specific Patient Populations

Dose adjustment is not required for elderly patients or patients with mild to moderate hepatic impairment. There are no data on the pharmacokinetic profile of montelukast in patients with severe hepatic impairment (Child-Pugh score over 9).

Studies in patients with renal impairment have not been conducted. Since montelukast and its metabolites are eliminated via bile, dose adjustment in patients with renal impairment is not considered necessary.

Administration of high doses of montelukast (20 and 60 times the recommended adult dose) was associated with decreased plasma concentrations of theophylline. This effect was not observed with the recommended dose of 10 mg once daily.

Pharmacokinetic studies of montelukast have shown that the concentration profiles of 4 mg chewable tablets in children aged 2 to 5 years are similar to the concentration profiles of 10 mg coated tablets in adults. The 4 mg chewable tablets are indicated for use in patients aged 2 to 5 years.

Clinical characteristics.

Indications.

For children aged 2 to 5 years:

• as add-on therapy for mild to moderate persistent bronchial asthma that is not adequately controlled by inhaled corticosteroids, and in cases of inadequate clinical control of asthma symptoms with short-acting β-agonists used as needed;
• as an alternative to low-dose inhaled corticosteroids in patients with mild persistent asthma who have not recently experienced severe asthma attacks requiring oral corticosteroids, and in patients who cannot use inhaled corticosteroids;
• prevention of asthma in which bronchospasm induced by physical exertion is the predominant component;
• relief of symptoms of seasonal and perennial allergic rhinitis.

Contraindications.

Hypersensitivity to montelukast or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Montelukast may be administered concomitantly with other medications used for the prevention or long-term treatment of bronchial asthma. The recommended clinical dose of montelukast has no significant clinical effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethindrone 35/1), terfenadine, digoxin, and warfarin.

In patients concurrently taking phenobarbital, the area under the concentration-time curve (AUC) for montelukast decreased by approximately 40%. Since montelukast is metabolized by CYP 3A4, 2C8, and 2C9, caution should be exercised, especially in children, when montelukast is administered concomitantly with inducers of CYP3A4, 2C8 and 2C9, such as phenytoin, phenobarbital, rifampicin.

In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. Drug interaction studies involving montelukast and rosiglitazone (a drug metabolized by CYP 2C8) demonstrated that montelukast is not an inhibitor of CYP 2C8 in vivo. Therefore, montelukast does not significantly affect the metabolism of drugs metabolized by CYP 2C8 (e.g., paclitaxel, rosiglitazone, and repaglinide).

In vitro studies have shown that montelukast is a substrate of CYP 2C8 and, to a lesser extent, of CYP 2C9 and 3A4. In a clinical drug interaction study of montelukast and gemfibrozil (an inhibitor of CYP 2C8 and 2C9), gemfibrozil increased systemic exposure to montelukast by 4.4-fold. When montelukast is used concomitantly with gemfibrozil or other potent inhibitors of CYP 2C8, dose adjustment of montelukast is not required; however, physicians should consider the increased risk of adverse reactions.

Based on in vitro studies, clinically significant interactions are not expected with weaker inhibitors of CYP2C8 (e.g., trimethoprim).

Concomitant administration of montelukast with itraconazole (a potent CYP 3A4 inhibitor) did not result in a significant increase in systemic exposure to montelukast.

Special precautions for use

Patients should be warned that Asmont should not be used to relieve acute asthmatic attacks and should always have a suitable rescue medication readily available. In the case of an acute attack, short-acting inhaled β-agonists should be used. Patients should seek medical advice as soon as possible if they require a greater than usual number of doses of short-acting β-agonists.

Inhaled or oral corticosteroids should not be abruptly replaced with montelukast.

There are no data demonstrating that the dose of oral corticosteroids can be reduced when montelukast is taken concomitantly.

Neuropsychiatric events have been reported in adult patients, adolescents, and children taking montelukast (see section "Adverse reactions"). Patients and physicians should be aware of the possibility of neuropsychiatric events. Physicians should discuss the potential for such events with their patients and/or their caregivers. Patients and/or caregivers should be instructed to inform their physician if neuropsychiatric changes occur. Physicians should carefully evaluate the risks and benefits of continuing montelukast therapy if such events occur.

In isolated cases, systemic eosinophilia, sometimes manifesting clinically as vasculitis, such as Churg-Strauss syndrome (allergic granulomatous angiitis), has been observed in patients receiving anti-asthma medications, including montelukast. This condition is typically treated with systemic corticosteroids. These cases usually, but not always, occurred in association with a reduction or discontinuation of oral corticosteroid therapy. A causal relationship between leukotriene receptor antagonists and the development of Churg-Strauss syndrome cannot be either ruled out or confirmed. Therefore, physicians should remain alert to the possibility of eosinophilia, vasculitic rash, worsening of pulmonary symptoms, cardiovascular complications, and/or neuropathy in their patients. Patients who develop the aforementioned symptoms should undergo re-evaluation, and their treatment regimen should be reviewed.

Treatment with montelukast does not eliminate the need for patients with aspirin-induced bronchial asthma to avoid acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.

Asmont chewable tablets contain aspartame, a phenylalanine derivative, which is harmful to patients with phenylketonuria. Patients with phenylketonuria should be aware that one 4 mg tablet of Asmont contains 0.6 mg of aspartame.

Use during pregnancy or breastfeeding.

Pregnancy. Animal studies have not demonstrated any harmful effects on pregnancy or embryonic/fetal development.

Available data from published prospective and retrospective cohort studies on the use of montelukast in pregnant women, assessing significant congenital malformations in offspring, have not established a risk associated with the use of the medicinal product. However, the existing studies have methodological limitations, including small sample size, retrospective data collection in some cases, and non-comparable control groups.

Asmont may be used during pregnancy only if it is considered absolutely necessary.

Breastfeeding. Studies in rats have shown that montelukast passes into milk. It is unknown whether montelukast/metabolites are excreted in human breast milk.

Asmont may be used during breastfeeding only if it is considered absolutely necessary.

Ability to affect reaction speed when driving or operating machinery.

Montelukast is not expected to affect a patient's ability to drive or operate machinery. However, very rare cases of somnolence or dizziness have been reported; therefore, caution should be exercised when driving or operating machinery during treatment.

Method of Administration and Dosage

The medication should be administered under adult supervision. The tablets should be chewed before swallowing.

For patients with bronchial asthma and allergic rhinitis (seasonal and perennial), the recommended dose is 1 chewable tablet of 4 mg once daily. To alleviate symptoms of allergic rhinitis, the time of administration should be individually adjusted.

For the treatment of bronchial asthma, the dose for children aged 2 to 5 years is 1 chewable tablet (4 mg) once daily in the evening, 1 hour before or 2 hours after a meal. Dose adjustment is not required for this age group. The medication Asmont in the form of 4 mg chewable tablets is not recommended for children under 2 years of age.

General Recommendations

The therapeutic effect of the medication on bronchial asthma control parameters occurs within 1 day. Patients should be advised to continue taking Asmont even after achieving asthma control, as well as during asthma exacerbations.

Dose adjustment is not necessary for patients with renal impairment or mild to moderate hepatic impairment. There are no data regarding dose adjustment in patients with severe hepatic impairment.

The dosage of the medication is the same for male and female patients.

As an alternative treatment instead of low-dose inhaled corticosteroids in mild persistent asthma

Montelukast is not recommended as monotherapy for patients with moderate persistent bronchial asthma. The decision to use montelukast as an alternative to low-dose inhaled corticosteroids in children aged 2 to 5 years with mild persistent asthma may be considered only for patients who have not experienced severe asthma attacks requiring oral corticosteroids in the recent past, and for patients who have demonstrated inability to use inhaled corticosteroids.

Mild persistent asthma is defined as asthma symptoms occurring more than once a week but less than once a day, nocturnal symptoms occurring more than twice a month but less than once a week, and normal lung function between episodes.

If satisfactory asthma control is not achieved within 1 month of montelukast therapy, the need for additional or alternative anti-inflammatory therapy should be evaluated based on a stepwise approach to bronchial asthma management. Patients should be periodically monitored to assess asthma control.

Prevention of asthma in patients aged 2 to 5 years in whom the primary component of asthma is exercise-induced bronchoconstriction

Asmont is recommended for patients aged 2 to 5 years for the prevention of exercise-induced bronchoconstriction, which may be the primary manifestation of persistent asthma requiring inhaled corticosteroid therapy. The patient's condition should be evaluated after 2–4 weeks of montelukast treatment. If an adequate response is not achieved, additional or alternative therapy should be considered.

Use of montelukast in combination with other asthma treatments

When montelukast is used as add-on therapy to inhaled corticosteroids, inhaled corticosteroids must not be abruptly replaced with montelukast.

Children

For use in children aged 2 to 5 years.

Overdose

During long-term studies in chronic bronchial asthma, montelukast was administered at doses up to 200 mg/day in adult patients, and in short-term studies at doses up to 900 mg/day for approximately one week, without clinically significant adverse reactions.

Symptoms Acute montelukast overdose has been reported. These cases involved adults and children who ingested doses exceeding 1000 mg (approximately 61 mg/kg in a 42-month-old child). Observed clinical and laboratory findings were within the safety profile established in adult and pediatric patients. In most cases, no adverse reactions were reported. The most commonly observed adverse reactions were consistent with the safety profile of montelukast and included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.

Treatment There is no specific information on the treatment of montelukast overdose. Treatment is symptomatic. No antidote is available. It is unknown whether montelukast is eliminated via peritoneal dialysis or hemodialysis.

Adverse Reactions

During clinical studies, the following adverse reactions were reported as common (≥ 1/100 to < 1/10) in patients receiving montelukast treatment and more frequently than in patients receiving placebo:

Nervous system: headache.

Gastrointestinal system: abdominal pain.

General disorders: thirst.

During long-term clinical treatment across various age groups, the safety profile remained unchanged.

Adverse reactions reported during the post-marketing period:

Infections and infestations: very common – upper respiratory tract infections*.

Blood and lymphatic system: rare – tendency toward increased bleeding; very rare – thrombocytopenia.

Immune system: uncommon – hypersensitivity reactions, including anaphylaxis; very rare – hepatic eosinophilic infiltration.

Psychiatric disorders: uncommon – sleep disorders, including nightmares, insomnia, somnambulism, anxiety, agitation, including aggressive behavior or hostility, depression, psychomotor hyperactivity (including irritability, restlessness, tremor§); rare – attention disorders, memory impairment, tic; very rare – hallucinations, disorientation, suicidal thoughts and behavior (suicidality), dysphemia, obsessive-compulsive disorders.

Nervous system: uncommon – dizziness, drowsiness, paresthesia/hypoaesthesia, seizures.

Cardiac system: rare – palpitations.

Respiratory, thoracic and mediastinal system: uncommon – epistaxis; very rare – Churg-Strauss syndrome (see section "Special precautions for use"), pulmonary eosinophilia.

Gastrointestinal system: common – diarrhea**, nausea**, vomiting**; uncommon – dry mouth, dyspepsia.

Hepatobiliary system: common – increased serum transaminase levels (ALT, AST); very rare – hepatitis (including cholestatic, hepatocellular, and mixed liver injury).

Skin and subcutaneous tissue: common – rash**; uncommon – bruising, urticaria, pruritus; rare – angioedema; very rare – erythema nodosum, erythema multiforme.

Musculoskeletal and connective tissue: uncommon – arthralgia, myalgia, including muscle cramps.

Renal and urinary system: uncommon – enuresis in children.

General disorders: common – pyrexia**; uncommon – asthenia/fatigue, discomfort (malaise), swelling.

Frequency categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000).

* This adverse reaction was observed at a "very common" frequency in patients treated with montelukast as well as in patients receiving placebo during clinical studies.

** This adverse reaction was observed at a "common" frequency in patients treated with montelukast as well as in patients receiving placebo during clinical studies.

§ Frequency category: rare.

Shelf life.

3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

7 tablets in a blister; 4 blisters in a carton.

Prescription category. Prescription only.

Manufacturer.

Limited liability company "Agrofarm".

Limited liability company "Natur+".

Manufacturer's location and address of business activity.

Ukraine, 08200, Kyiv region, Irpin, Central Street, 113-A.

Ukraine, 08200, Kyiv region, Irpin, Taras Shevchenko Street, 3.