Instructions Montel film-coated tablets 10 mg blister No. 28
Composition
active ingredient: montelukast sodium;
1 tablet contains montelukast sodium 10.4 mg, equivalent to montelukast 10.0 mg;
excipients: microcrystalline cellulose, lactose monohydrate, low-substituted hydroxypropylcellulose, croscarmellose sodium, magnesium stearate;
Opadry I yellow film coating: hypromellose, hydroxypropylcellulose, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, from light yellow to yellow with a faint brown tint, round in shape, with a biconvex surface. The surface of the tablets contains an imprint of "M9UT" and "10" on one side.
Pharmacotherapeutic group
Means for systemic use in obstructive airway diseases. Leukotriene receptor blockers.
ATX code R03D C03.
Pharmacological properties
Pharmacodynamics
Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids secreted by various cells, including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl leukotriene receptors (CysLT) present in the human airways (including smooth muscle myocytes and macrophages) and other pro-inflammatory cells (including eosinophils and some myeloid stem cells). CysLTs are implicated in the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, sputum production, vascular permeability, and increased eosinophil numbers. In allergic rhinitis, CysLT is released from the nasal mucosa during both phases (early and late) following allergen exposure and is manifested by the symptoms of allergic rhinitis. An intranasal challenge with CysLT has demonstrated an increase in nasal airway resistance and symptoms of nasal obstruction.
Montelukast is an active compound that binds with high selectivity and chemical affinity to CysLT1 receptors. Montelukast produces significant blockade of airway cysteinyl leukotriene receptors, as demonstrated by its ability to inhibit LTD4-induced bronchoconstriction in asthmatic patients. Even a low dose of 5 mg produces significant blockade of LTD4-induced bronchoconstriction. Montelukast produces bronchodilation within 2 hours after oral administration; this effect was additive to that produced by β-agonists.
Treatment with montelukast suppresses both early and late-stage bronchospasm by reducing the response to antigens. Montelukast reduces peripheral blood eosinophil counts in adult and pediatric patients, significantly reduces airway eosinophil counts (sputum analysis), and improves clinical control of asthma.
Pharmacokinetics
Absorption. After oral administration, montelukast is rapidly and almost completely absorbed. In adults, when taking film-coated tablets in a dose of 10 mg on an empty stomach, the maximum concentration Cmax in plasma is reached after 3 hours (Tmax). The average bioavailability is 64%. Taking a regular meal does not affect the Cmax in plasma and the bioavailability of film-coated tablets.
Distribution: Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8 to 11 liters. In studies of radiolabeled montelukast, passage across the blood-brain barrier was minimal. In all other tissues, radiolabeled material concentrations were also minimal 24 hours after dosing.
Metabolism: Montelukast is extensively metabolized. Steady-state plasma concentrations of montelukast metabolites have not been determined in studies using therapeutic doses in adults and pediatric patients.
In vitro studies using human liver microsomes have shown that cytochromes P450 3A4, 2A6, and 2C9 are involved in the metabolism of montelukast. Further in vitro studies using human liver microsomes have shown that at therapeutic concentrations, montelukast does not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, and 2D6. The contribution of metabolites to the therapeutic effects of montelukast is 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 the feces within 5 days and less than 0.2% in the urine. This, together with the oral bioavailability of montelukast, indicates that its metabolites are almost entirely excreted in the bile.
Pharmacokinetics in different patient groups. No dose adjustment is 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 greater than 9).
A decrease in plasma theophylline concentrations was observed at high doses of montelukast (20 and 60 times the recommended adult dose). This effect was not observed at the recommended dose of 10 mg once daily.
Indication
Additional treatment of persistent bronchial asthma of mild to moderate severity, insufficiently controlled by inhaled corticosteroids, as well as in case of insufficient clinical control of asthma with short-acting β-agonists used as needed.
Symptomatic treatment of seasonal allergic rhinitis in patients with bronchial asthma.
Prevention of bronchial asthma, the dominant component of which is exercise-induced bronchospasm.
Relief of symptoms of seasonal and perennial allergic rhinitis. The risks of psychoneurological symptoms in patients with allergic rhinitis may outweigh the benefits of montelukast, so montelukast should be used as a reserve drug for patients with inadequate response to or intolerance to alternative therapy.
Contraindication
Hypersensitivity to montelukast or to any other component of the drug.
Children under 15 years of age (for a dose of 10 mg).
Interaction with other medicinal products and other types of interactions
Montelukast can be administered with other drugs for the prevention or long-term treatment of bronchial asthma. The recommended clinical dose of montelukast has no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethindrone 35/1), terfenadine, digoxin, and warfarin.
In patients receiving concomitant phenobarbital, the area under the concentration-time curve (AUC) for montelukast was 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 CYP 3A4, 2C8, and 2C9, such as phenytoin, phenobarbital, and rifampicin.
In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. Drug interaction studies involving montelukast and rosiglitazone (a marker substrate; a drug metabolized by CYP 2C8) have shown 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, 2C9 and 3A4. In a clinical interaction study of montelukast and gemfibrozil (an inhibitor of CYP 2C8 and 2C9), gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. No dose adjustment of montelukast is required when used concomitantly with gemfibrozil or other potent inhibitors of CYP 2C8, but the physician should consider the increased risk of adverse reactions.
Based on in vitro studies, no clinically significant interactions are expected with less potent CYP 2C8 inhibitors (e.g. trimethoprim).
Co-administration of montelukast with itraconazole (a potent CYP 3A4 inhibitor) did not result in a significant increase in systemic exposure to montelukast.
Application features
Patients should be advised that Montelukast should not be used to relieve acute asthma attacks and that they should always carry appropriate rescue medication with them. In the event of an acute attack, a short-acting inhaled β-agonist should be used. Patients should consult their doctor as soon as possible if they require more inhalations of short-acting β-agonists than usual.
Montelukast should not be abruptly substituted for inhaled or oral corticosteroids. Montelukast should not be taken with medications that also contain montelukast.
There is no evidence to suggest that the dose of oral corticosteroids can be reduced when montelukast is co-administered.
In isolated cases, patients receiving anti-asthma drugs, including montelukast, may experience systemic eosinophilia, sometimes with clinical manifestations of vasculitis, the so-called Churg-Strauss syndrome (granulomatous allergic angiitis), which is treated with systemic corticosteroids. Such cases have usually been associated with a reduction in the dose or withdrawal of oral corticosteroids. The association of leukotriene receptor antagonists with the development of Churg-Strauss syndrome can neither be refuted nor confirmed, so physicians should be aware of the possibility of eosinophilia, vasculitic rashes, worsening pulmonary symptoms, cardiovascular complications and/or neuropathy in patients. Patients who develop the above symptoms should be re-evaluated and their treatment regimen should be reviewed.
Treatment with montelukast does not eliminate the need for patients with aspirin-dependent bronchial asthma to avoid the use of aspirin or other nonsteroidal anti-inflammatory drugs.
Montel film-coated tablets should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Use during pregnancy or breastfeeding
Animal studies have not shown harmful effects on pregnancy or embryonal/fetal development.
Prospective and retrospective cohort studies of montelukast in pregnant women evaluating major birth defects have not identified a drug-related risk. However, these studies have methodological limitations, including small sample sizes, retrospective data collection in some cases, and inadequate comparison groups.
Montel can be used during pregnancy only if it is considered absolutely necessary.
Animal studies have shown that montelukast passes into breast milk. It is not known whether montelukast passes into human breast milk. Montelukast should be used during breastfeeding only if considered clearly necessary.
Ability to influence reaction speed when driving vehicles or other mechanisms
Montelukast is not expected to affect the patient's ability to drive or use machines. However, dizziness or drowsiness may occur in isolated cases.
Method of administration and doses
The medicine should be taken orally, regardless of meals.
Adults and children aged 15 years and over for the treatment of asthma or asthma with concomitant seasonal allergic rhinitis should take 1 tablet (10 mg) once a day, in the evening.
General recommendations.
The therapeutic effect of the drug on the control of bronchial asthma occurs within 1 day. Patients should be advised to continue taking the drug even when bronchial asthma control is achieved, as well as during periods of exacerbation of asthma. The drug should not be taken together with drugs that also contain montelukast.
No dose adjustment is necessary in elderly patients, patients with renal impairment, or patients with mild to moderate hepatic impairment. There are no data in patients with severe hepatic impairment.
The dosage of the drug is the same for male and female patients.
Montelukast treatment depends on other methods of treating bronchial asthma.
Montel can be prescribed in addition to the patient's current course of treatment.
Inhaled corticosteroids.
Montelukast may be used as add-on therapy when inhaled corticosteroids in combination with short-acting β-agonists as first-line therapy do not provide adequate clinical control of the disease.
You should not abruptly replace inhaled corticosteroids with Montelukast.
Children
Use in children over 15 years of age. Children under 15 years of age should use the drug in the form of chewable tablets.
Overdose
In long-term studies of chronic bronchial asthma, montelukast was administered in doses up to 200 mg/day to adult patients, and in short-term studies up to 900 mg/day for approximately one week, without clinically significant adverse reactions.
Symptoms: Acute overdose of montelukast has been reported. These cases involved adults and children who received doses in excess of 1000 mg (approximately 61 mg/kg in a 42-month-old child). Clinical and laboratory parameters were within the safety profile in adults and children. In most cases of overdose, no adverse reactions were reported. The most frequently 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 overdose with montelukast. Treatment is symptomatic. There is no antidote. It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis.
Adverse reactions
The following adverse reactions have been observed during clinical trials and post-marketing experience. 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: rarely - a tendency to increased bleeding, very rarely - thrombocytopenia.
Immune system: infrequently - hypersensitivity reactions, including anaphylaxis, very rarely - eosinophilic infiltration of the liver.
Psychiatric disorders: uncommon - sleep disorders, including nightmares, insomnia, somnabulism, anxiety, agitation, including aggressive behavior or hostility, psychomotor hyperactivity (including irritability, restlessness, tremor), depression; rare - disturbance in attention, memory impairment/loss, tic; very rare - dysphemia, hallucinations, disorientation, suicidal thoughts and behavior (suicide attempts), obsessive-compulsive disorder.
Nervous system: often - headache, infrequently - lethargy, dizziness, drowsiness, paresthesias/hypoesthesias, convulsions.
Cardiovascular system: rarely - feeling of heartbeat (palpitations).
Respiratory system: uncommon - epistaxis, very rare - pulmonary eosinophilia. Isolated cases of Churg-Strauss syndrome have been reported in patients with bronchial asthma.
Digestive system: often - abdominal pain, diarrhea**, nausea**, vomiting**, infrequently - dyspepsia, dry mouth, feeling of thirst.
Hepatobiliary system: often - increased serum transaminase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), very rarely - hepatitis (including cholestatic, hepatocellular, liver damage of mixed genesis).
Skin and subcutaneous tissue: often - rash**, infrequently - hematomas, urticaria, itching, rarely - angioedema, very rarely - erythema nodosum, erythema multiforme.
Urinary system: uncommon – enuresis in children.
Musculoskeletal system and connective tissue: uncommon - arthralgia, myalgia, including muscle spasms.
Infections and infestations: very common – upper respiratory tract infections*.
General disorders: common: pyrexia**, uncommon: asthenia/fatigue, malaise, edema.
*This adverse reaction was observed with a frequency of “very common” in patients taking montelukast, as well as in patients taking placebo, during clinical trials.
**This adverse reaction was observed with a frequency of “common” in patients taking montelukast, as well as in patients taking placebo, during clinical trials.
This adverse reaction was observed with a frequency of "rare".
Expiration date
3 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
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 pack.
Vacation category
According to the recipe.
Producer
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant".
Location of the manufacturer and its business address
Ukraine, 03134, Kyiv, Myru St., 17.
