Montel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MONTÉL (MONTEL)

Composition:

Active substance: montelukast sodium;

1 tablet contains montelukast sodium 4.16 mg, equivalent to 4.0 mg of montelukast;

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

Pharmaceutical form. Chewable tablets.

Main physicochemical properties: oval-shaped, biconvex tablets, pink in color*. The surface of the tablets bears the imprint "M9UT 4" on one side.

* Speckles may be present 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 key pro-asthmatic mediators bind to cysteinyl leukotriene receptors (CysLT) present in human airways and cause responses such as bronchoconstriction, mucus secretion, increased vascular permeability, and eosinophil recruitment.

Montelukast is an active compound that selectively and with high affinity binds 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 substantial blockade of LTD4-stimulated bronchoconstriction. Montelukast induces bronchodilation within 2 hours after 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 allergens. Montelukast reduces the number of eosinophils in peripheral blood in adult and pediatric patients, significantly decreases eosinophil counts in the airways (sputum analysis), and improves clinical asthma control.

Pharmacokinetics

Absorption. After administration, montelukast is rapidly and almost completely absorbed. Following a single 4 mg chewable tablet dose taken on an empty stomach in children aged 2 to 5 years, Cmax is reached within 2 hours after administration. The mean oral bioavailability is 73% and decreases to 63% when taken with food. The mean Cmax is 66% higher and the mean Cmin 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. Concentrations of radiolabeled material in all other tissues 24 hours after dose administration were also found to be 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.

Elimination. The plasma clearance of montelukast in healthy adult volunteers averages 45 mL/min. Following 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 pharmacokinetics of montelukast in patients with severe hepatic impairment (Child-Pugh score >9).

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

Decreased plasma concentrations of theophylline have been observed following administration of high doses of montelukast (20- and 60-fold higher than the recommended adult dose). 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 those 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 patients with inadequate clinical control of asthma symptoms using short-acting β-agonists on an as-needed basis;
• 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 those patients who cannot use inhaled corticosteroids;
• prevention of asthma with exercise-induced bronchospasm as the predominant component;
• relief of symptoms of seasonal and perennial allergic rhinitis. The risk of developing neuropsychiatric symptoms in patients with allergic rhinit游戏副本

Special precautions for use.

Patients should be warned that Montel should not be used to relieve acute asthmatic attacks, and that they must always have access to a suitable rescue medication. In the event of an acute attack, short-acting inhaled β-agonists should be used. Patients should seek immediate medical advice if they find they need more short-acting β-agonist inhalations than usual.

Montelukast should not be used to abruptly replace inhaled or oral corticosteroids.

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

The drug should not be taken together with medicinal products that also contain montelukast.

Psychoneuropsychiatric events have been reported in adult patients, adolescents, and children taking montelukast (see section "Adverse reactions"). Patients and physicians should remain alert for the possible occurrence of such events. Patients and/or caregivers should be instructed to inform their physician if any psychoneuropsychiatric symptoms develop. Physicians should carefully evaluate the risks and benefits of continuing montelukast therapy if such events occur.

In rare cases, systemic eosinophilia, sometimes manifesting clinically as vasculitis, has been observed in patients receiving anti-asthma medications, including montelukast. This condition is known as Churg-Strauss syndrome (allergic granulomatous angiitis), which is typically treated with systemic corticosteroids. These cases have often been associated with a reduction or withdrawal of oral corticosteroid therapy. A causal relationship between leukotriene receptor antagonists and the development of Churg-Strauss syndrome cannot be definitively ruled out or confirmed. Therefore, physicians should be aware of the possibility of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiovascular complications, and/or neuropathy in 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 the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

Montel chewable tablets contain aspartame, a source of phenylalanine. Patients with phenylketonuria should be informed that each 4 mg tablet contains aspartame equivalent to 0.674 mg of phenylalanine.

Use during pregnancy or breastfeeding.

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

Data from 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 drug. However, these studies have methodological limitations, including small sample size, retrospective data collection in some cases, and inadequate control groups.

Montel may be used during pregnancy only if clearly necessary.

Studies in rats have shown that montelukast is excreted in milk. It is unknown whether montelukast is excreted in human breast milk. Montel may be used during breastfeeding only if clearly necessary.

Ability to influence reaction rate 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.

Dosage and Administration.

The medicinal product should be used in children under adult supervision.

For patients with 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 asthma, the dose for children aged 2 to 5 years is 1 chewable tablet (4 mg) once daily in the evening, taken 1 hour before or 2 hours after a meal. Dose adjustment is not required for this age group. The medicinal product Montel 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 medicinal product on parameters of asthma control develops within 1 day. Patients should be advised to continue taking the medication even after achieving asthma control and during asthma exacerbations.

Dose adjustment is not required for patients with renal impairment or mild to moderate hepatic impairment. There are no data available for patients with severe hepatic impairment.

Dosage of the drug is the same for male and female patients.

Alternative to low-dose inhaled corticosteroids in mild persistent asthma.

Montelukast is not recommended as monotherapy for patients with moderate persistent 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 those 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 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 treatment should be evaluated based on a stepwise approach to asthma management. Patients should be regularly monitored to assess asthma control.

Prophylactic use prior to physical exertion in patients aged 2 to 5 years to prevent asthma attacks.

Exercise-induced bronchospasm may be the main manifestation of persistent asthma requiring treatment with inhaled corticosteroids. The patient's condition should be evaluated 2 to 4 weeks after initiation of montelukast therapy. If a satisfactory treatment response is not observed, a decision regarding additional or alternative therapy should be made.

Montelukast therapy in combination with other asthma treatments.

When montelukast therapy is used as add-on treatment to inhaled corticosteroids, inhaled corticosteroids should not be abruptly replaced by montelukast.

Children.

For use in children aged 2 to 5 years.

Overdose.

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

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). The observed clinical and laboratory findings were within the safety profile of montelukast in adult and pediatric patients. In most cases, no adverse reactions were reported.

Symptoms. 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 removed by peritoneal dialysis or hemodialysis.

Adverse reactions.

Long-term treatment across various age groups in clinical studies has demonstrated a consistent safety profile.

The adverse reactions listed below were observed during clinical trials and in the post-marketing period. Adverse reactions are classified by frequency: common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000).

Blood and lymphatic system disorders: rare – tendency to increased bleeding, very rare – thrombocytopenia.

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

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

Nervous system disorders: common – headache; uncommon – lethargy, dizziness, somnolence, paresthesia/hypoesthesia, convulsions.

Cardiac disorders: rare – palpitations.

Respiratory system: uncommon – epistaxis; very rare – pulmonary eosinophilia. Isolated cases of Churg-Strauss syndrome have been reported in patients with bronchial asthma.

Gastrointestinal disorders: common – abdominal pain, diarrhea**, nausea**, vomiting**; uncommon – dyspepsia, dry mouth, thirst.

Hepatobiliary disorders: common – increased serum transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]); very rare – hepatitis (including cholestatic, hepatocellular, mixed-type liver injury).

Skin and subcutaneous tissue disorders: common – rash**; uncommon – bruising, urticaria, pruritus; rare – angioneurotic edema; very rare – nodular erythema, erythema multiforme.

Renal and urinary disorders: uncommon – enuresis in children.

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

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

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

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

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

§This adverse reaction was observed with a frequency of "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 pack, 4 blisters per carton.

Prescription category. Prescription only.

Manufacturer.

Public Joint-Stock Company "Scientific-Production Center "Borshchahivskiy Chemical-Pharmaceutical Plant".

Manufacturer's location and address of business activity.

17 Miru Street, Kyiv, 03134, Ukraine.