Instructions Montular film-coated tablets 10 mg blister No. 30
Composition
active ingredient: montelukast sodium;
1 tablet contains montelukast sodium equivalent to montelukast 10 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate, Opadry 20A520035 yellow coating: hydroxypropylcellulose, hypromellose, titanium dioxide (E 171), carnauba wax, yellow iron oxide (E 172), red iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: beige colored, round, biconvex, smooth on both sides, film-coated tablets.
Pharmacotherapeutic group
Means for systemic use in obstructive airway diseases. Leukotriene receptor blockers. ATC 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 and induce responses such as bronchospasm, hypersecretion, increased vascular permeability, and increased eosinophil numbers.
Montelukast is an orally administered active compound that binds with high selectivity and affinity to CysLT1 receptors. In clinical studies, montelukast has been shown to inhibit bronchospasm following inhalation of 5 mg of LTD4. Bronchodilation was observed within 2 hours after oral administration, and this effect was additive to that induced by β-agonists. Treatment with montelukast inhibited both the early and late phases of antigen-induced bronchoconstriction. There is clinical evidence that montelukast significantly reduced peripheral blood and airway eosinophil counts (as measured in sputum) and improved clinical control of asthma.
Pharmacokinetics
Absorption.
Montelukast is rapidly absorbed after oral administration. After administration of 10 mg film-coated tablets to adults in the fasted state, mean peak plasma concentrations (Cmax) were achieved at 3 hours (Tmax). Mean oral bioavailability was 64%. Oral bioavailability and Cmax were not affected by food intake. Safety and efficacy were demonstrated in clinical studies with 10 mg film-coated tablets administered without regard to mealtime.
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 in rats with radiolabeled montelukast, passage across the blood-brain barrier was minimal. In addition, radiolabeled material concentrations in all other tissues were also minimal 24 hours after dosing.
Metabolism.
Montelukast is extensively metabolized. Steady-state plasma concentrations of montelukast metabolites were not determined in studies using therapeutic doses in adults and pediatric patients.
Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. In addition, cytochromes CYP 3A4 and 2C9 play a minor role in the metabolism of montelukast, although itraconazole (a CYP 3A4 inhibitor) did not alter the pharmacokinetics of montelukast in healthy volunteers given 10 mg of montelukast daily. In vitro studies using human liver microsomes indicate that therapeutic plasma concentrations of montelukast do not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, and 2D6. The contribution of metabolites to the therapeutic effects of montelukast is minimal.
Breeding.
The plasma clearance of montelukast in healthy adult volunteers averages 45 mL/min. After oral administration 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 montelukast and its metabolites are almost entirely excreted in the bile.
Pharmacokinetics in different patient groups.
No dose adjustment is necessary for patients with mild to moderate hepatic impairment. Studies in patients with renal impairment have not been conducted. Since montelukast and its metabolites are excreted in the bile, dose adjustment is not considered necessary for patients with renal 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 has been observed at high doses of montelukast (20 and 60 times the recommended adult dose). This effect is not observed at the recommended dose of 10 mg once daily.
Indication
As an add-on treatment for bronchial asthma in patients with mild to moderate persistent asthma inadequately controlled with inhaled corticosteroids, and in patients with inadequate clinical control of asthma with short-acting β-adrenergic agonists used as needed. In patients with asthma taking Montular®, this drug also relieves symptoms of seasonal allergic rhinitis.
Prevention of asthma, the dominant component of which is exercise-induced bronchospasm.
Relief of symptoms of seasonal and perennial allergic rhinitis.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the drug.
Children under 15 years old.
Interaction with other medicinal products and other types of interactions
Montelukast can be administered with other drugs commonly used for the prevention or long-term treatment of asthma. In drug-drug interaction studies, montelukast at the recommended clinical dose had no clinically important 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. However, data from a clinical drug interaction study 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 this enzyme (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 drug interaction study with montelukast and gemfibrozil (an inhibitor of CYP2C8 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 CYP2C8 inhibitors (e.g. trimethoprim). Coadministration 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 Montular® should never be used to treat acute asthma attacks and that they should always carry appropriate rescue medication with them. In the event of an acute attack, inhaled short-acting β-agonists should be used. Patients should consult their doctor as soon as possible if they require more short-acting β-agonists than usual.
Montelukast therapy should not be abruptly replaced with inhaled or oral corticosteroid medications.
There is no evidence to suggest that the dose of oral corticosteroids can be reduced when montelukast is co-administered.
Neuropsychiatric events have been reported in patients taking montelukast (see Adverse Reactions). Because these events may be influenced by other factors, it is not known whether these events are related to montelukast. Physicians should discuss these adverse events with their patients and/or caregivers. Patients and/or caregivers should be instructed to notify their physician of any such changes.
In isolated cases, patients receiving anti-asthma agents, including montelukast, may experience systemic eosinophilia, sometimes with clinical manifestations of vasculitis, the so-called Churg-Strauss syndrome, which is treated with systemic corticosteroid therapy. Such cases have usually (but not always) been associated with a reduction in the dose or withdrawal of the corticosteroid. The possibility that leukotriene receptor antagonists may be associated with the development of Churg-Strauss syndrome cannot be ruled out or confirmed. Physicians should be aware of the possibility that patients may develop eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications and/or neuropathy. Patients who develop such symptoms should be re-evaluated and their treatment regimen reviewed.
Montelukast treatment prevents patients with aspirin-dependent asthma from using aspirin or other nonsteroidal anti-inflammatory drugs.
Use during pregnancy or breastfeeding
Limited pregnancy database information does not indicate a causal relationship between the use of montelukast and the occurrence of malformations (such as limb defects), which have been rarely reported during worldwide post-marketing experience.
Montelukast can be taken during pregnancy only if, in the opinion of the doctor, the expected benefit to the woman outweighs the possible risk to the fetus.
Breastfeeding: Studies in rats have shown that montelukast is excreted in human milk. It is not known whether montelukast is excreted in human milk.
Montelukast can be used during breastfeeding only if, in the opinion of the doctor, the expected benefit to the mother outweighs the possible risk to the child.
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, drowsiness or dizziness have been reported very rarely.
Method of administration and doses
The dose for patients (aged 15 years and over) with asthma or with asthma and concomitant seasonal allergic rhinitis is 10 mg (1 tablet) per day, in the evening. To relieve the symptoms of allergic rhinitis, the time of administration is selected individually.
General recommendations. The therapeutic effect of montelukast on asthma control occurs within 1 day. The drug can be used regardless of food intake. Patients should be advised to continue taking Montular® even if asthma control is achieved, as well as during periods of asthma exacerbation. Montular® should not be used simultaneously with drugs containing the active substance montelukast.
No dose adjustment is necessary for elderly patients, patients with renal impairment, or patients with mild to moderate hepatic impairment. There are no data available for patients with severe hepatic impairment. The dosage is the same for men and women.
Treatment with Montular® depends on other asthma treatment.
Montular® can be added to the patient's existing treatment regimen.
Inhaled corticosteroids. Montular® can be used as an additional treatment in patients in whom inhaled corticosteroids together with short-acting β-agonists used as needed do not provide satisfactory clinical control of the disease.
Montular® should not be abruptly substituted for inhaled corticosteroids.
Children.
Used for children aged 15 and over.
Overdose
There is no specific information on the treatment of overdose with montelukast. In adult patients with chronic asthma, montelukast has been administered at doses up to 200 mg/day for 22 weeks in studies and in short-term studies at doses up to 900 mg/day for approximately 1 week without clinically significant adverse reactions.
Cases of acute overdose have been reported during post-marketing and clinical trials with montelukast. These cases have occurred in adults and children at doses exceeding 1000 mg (approximately 61 mg/kg in a 42-month-old child). Clinical and laboratory findings were consistent with the safety profile in adults and children. In most cases of overdose, 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.
It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis. Treatment is symptomatic.
Adverse reactions
Infections and infestations: upper respiratory tract infections.
Skin and subcutaneous tissue disorders: angioedema, hematoma, urticaria, pruritus, rash, erythema nodosum, erythema multiforme.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia, including muscle cramps.
Nervous system: headache, lethargy, drowsiness, dizziness, paresthesia/hypoesthesia, convulsions.
Gastrointestinal: abdominal pain, diarrhea, dry mouth, dyspepsia, nausea, vomiting.
Hepatobiliary system: increased serum transaminase levels (ALT, AST), hepatitis (including cholestatic, hepatocellular and mixed liver damage).
From the blood and lymphatic system: a tendency to increased bleeding.
Immune system disorders: hypersensitivity reactions, including anaphylaxis, eosinophilic infiltration of the liver.
Psychiatric: sleep disorders, including nightmares, insomnia, somnambulism, irritability, anxiety, agitation, restlessness, anger, impatience, excitement, including aggressive behavior or hostility, depression, tremor, hallucinations, suicidal thoughts and behavior (suicidality), psychomotor hyperactivity, tremor, disorientation, impaired attention, memory impairment.
Cardiovascular system: palpitations.
On the part of the respiratory system, thoracic organs and mediastinum: epistaxis, Churg-Strauss syndrome (CSS), pulmonary subtropical eosinophilia.
Renal and urinary disorders: enuresis in children.
General disorders and local reactions: asthenia/fatigue, malaise, feeling of discomfort, swelling, fever, thirst.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister, 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
KUSUM HEALTHCARE PVT LTD/KUSUM HEALTHCARE PVT LTD.
Location of the manufacturer and its business address
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India/SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
