INSTRUCTIONS FOR MEDICAL USE
Trade name of the drug: Astanol
Active substance (INN): Montelukast
Pharmaceutical form: coated tablets.
1 tablet contains:
Active ingredient: Montelukast sodium – 10.4 mg (equivalent to 10 mg of Montelukast).
Excipients: polyvinylpolypyrrolidone, microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, magnesium stearate, hydroxypropyl methylcellulose, polyethylene glycol-4000, titanium dioxide.
Description: Round biconvex white or almost white coated tablets.
Pharmacotherapeutic group: anti-inflammatory antibronchoconstrictor agents – leukotriene receptor blocker.
ATX code: R03DC03
Montelukast has a high affinity and selective binding to cysteinyl leukotriene receptors. Use of montelukast inhibits the early and late phases of bronchospasm. Montelukast reduces bronchospasm even at very low doses (5 mg). Bronchodilation continues for 2 hours after oral administration. The bronchodilation effect caused by the beta-adrenomimetic enhances the effect caused by montelukast. Montelukast reduces the number of eosinophils in the peripheral blood and airways (sputum) of children and adults and improves control of the clinical course of bronchial asthma. Montelukast enhances the clinical effects of inhaled glucocorticosteroids. Montelukast reduces the severity of daytime (including cough, wheezing, difficulty breathing and activity limitation) and nighttime symptoms of bronchial asthma. Montelukast reduces the need for beta-adrenomimetics and glucocorticosteroids used when necessary (when the condition worsens). Patients receiving montelukast have a longer remission than patients not taking it. A therapeutic effect is noted after the first dose. In children aged from 2 years with mild bronchial asthma and episodic exacerbations, montelukast significantly reduces the frequency of bronchial asthma exacerbations and improves respiratory function.
Bronchospasm arising against the background of physical activity is weakened. In patients with bronchial asthma who are sensitive to acetylsalicylic acid and taking concomitant therapy with inhaled and/or oral glucocorticosteroids, treatment with montelukast leads to a significant improvement in bronchial asthma symptom control.
The maximum plasma concentration of the substance (Cmax) was reached in children aged 2 to 5 years 2 hours after an empty stomach dose of 4 mg. The mean Cmax was 66% higher, while the mean Cmin was lower than in adults after a dose of 10 mg. In adult patients, when administered on an empty stomach at a dose of 5 mg, the Cmax was reached 2 hours after administration. The average bioavailability is 73%; it decreases to 63% when the drug is taken after a normal meal.
Montelukast is more than 99 % bound to plasma proteins. The volume of distribution of Montelukast in equilibrium is on average 8-11 liters. It penetrates poorly through the blood-brain barrier.
Montelukast undergoes active metabolism in the liver. In equilibrium after therapeutic doses, plasma concentrations of montelukast metabolites are undetectable in children and adults.
Cytochrome WA4, 2A6 and 2C9 isoenzymes are involved in the metabolism of montelukast, but at therapeutic concentrations, montelukast does not inhibit cytochrome isoenzymes WA4, 2C9, 1A2, 2A6, 2C19 and 2D6. Metabolites of montelukast have negligible pharmacological activity.
The plasma clearance of montelukast in healthy adults is on average 45 ml/min. After oral administration of labeled montelukast, 86% of the drug was excreted within 5 days via the intestine and less than 0.2% by the kidneys. This indicates that the drug and its metabolites are eliminated mainly with bile. The half-life (T1 / 2 ) of montelukast in young patients is 2.7 to 5.5 h. The pharmacokinetics of montelukast maintains an almost linear character when administered orally in doses over 50 mg. Special patient groups
Studies in patients with renal insufficiency have not been conducted. Because montelukast and its metabolites are excreted with bile, no dose adjustment is required in patients with renal insufficiency.
There are no data on the pharmacokinetics of montelukast in patients with severe hepatic impairment (Child-Pugh score > 9).
Indications for use
Treatment of bronchial asthma: as adjunctive treatment of bronchial asthma in patients with persistent asthma of mild to moderate severity, which is insufficiently controlled by inhaled corticosteroids, and in case of insufficient asthma control by short-acting β-agonists, administered when necessary. In patients with asthma taking the drug, the severity of symptoms of seasonal allergic rhinitis is also reduced.
Prevention of asthma, the main component of which is bronchospasm caused by physical activity. Reduction of the severity of symptoms of seasonal and year-round allergic rhinitis.
Dosage and administration
The dose for patients (from 15 years of age) with bronchial asthma or bronchial asthma with concomitant seasonal allergic rhinitis is 10 mg (1 tablet) once a day, in the evening, regardless of meals. In order to reduce the severity of symptoms of allergic rhinitis the time of drug administration should be adjusted individually. General recommendations. The therapeutic effect of the drug on bronchial asthma control parameters is 1 day. The drug can be used regardless of meals. Patients should be recommended to continue taking the drug even in case of achieving control of bronchial asthma symptoms, as well as during exacerbation of bronchial asthma.
The drug should not be used with other drugs containing the same active substance – montelukast.
Patients of elderly age, with renal or hepatic insufficiency of mild or moderate severity do not require dose adjustment. There are no data on patients with severe hepatic impairment. The drug doses for men and women are the same.
Treatment with the drug in dependence on other methods of bronchial asthma treatment.
The drug can be added to the existing course of treatment of the patient.
Inhaled corticosteroids: The drug may be used as an adjunctive treatment for patients in whom satisfactory clinical control of the disease is not achieved by using inhaled corticosteroids in combination with short-acting β-agonists when appropriate.
The drug should not abruptly replace inhaled corticosteroids.
Blood system disorders: increased tendency to bleeding.
Immune system: hypersensitivity reactions, including anaphylaxis; eosinophilic liver infiltrates.
Nervous system disorders: drowsiness, dizziness, paresthesia/hyperesthesia, seizures, headache, sleep disorders, including nightmares, hallucinations, psychomotor hyperactivity (including irritability, restlessness, agitation, including aggressive behavior, and tremor), depression and insomnia, suicidal thoughts and suicidal behavior.
Cardiovascular system: palpitations.
Gastrointestinal tract: diarrhea, dry mouth, dyspepsia, nausea and vomiting.
Hepatobiliary system: increased activity of “liver” transaminases in blood serum (alanine aminotransferase, aspartate aminotransferase), cholestatic hepatitis, pancreatitis.
Skin and subcutaneous tissue: angioedema, ecchymoses, urticaria, itching, rash, erythema nodosum, tendency to form bruises.
Musculoskeletal system: arthralgia, myalgia, including muscle cramps.
Other: asthenia/fatigue, discomfort, edema.
In very rare cases, against the background of taking montelukast, patients suffering from bronchial asthma develop Churg-Strauss syndrome.
- Hypersensitivity to Montelukast or any of the excipients of the drug.
- Childhood under 15 years of age.
The drug may be administered together with other drugs traditionally prescribed for prevention and long-term treatment of bronchial asthma. In recommended doses, the drug 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 area under the concentration-time curve (AUC) of montelukast in plasma was reduced by approximately 40% in patients who took montelukast and phenobarbital. Since CYP WA4 isoenzyme is involved in metabolism of montelukast, caution should be exercised, especially in children, when using montelukast with such CYP WA4 inducers as phenytoin, phenobarbital and rifampicin.
In in vitro studies it was found that montelukast is a potent inhibitor of CYP 2C8 isoenzyme. However, the results of clinical interaction studies of montelukast and rosiglitazone (an example of marker substrates for drugs whose main metabolism is carried out by CYP 2C8 isoenzyme) have not revealed the inhibitory effect of montelukast on CYP 2C8 isoenzyme in vivo. Therefore, it is expected that montelukast will not significantly alter the conversions of drugs that are metabolized with participation of this enzyme (e.g., paclitaxel, rosiglitazone and repaglinide).
When taking high doses of montelukast (at 20 and 60 times the recommended dose for adults), a decrease in plasma theophylline concentration is observed. This effect is not observed when taking the drug in the recommended doses.
Patients should not take the drug to relieve acute attacks of bronchial asthma. It is recommended to use inhaled beta-adrenomimetics when an attack occurs. If the need for short-acting beta-adrenomimetics increases, patients should consult a physician as soon as possible.
Inhaled or oral glucocorticosteroids should not be abruptly replaced with the drug.
There is no evidence to suggest that the dose of oral glucocorticosteroids may be reduced with concomitant use of the drug.
In rare cases, systemic eosinophilia, sometimes accompanied by clinical manifestations of vasculitis and Churg-Strauss syndrome, may occur in patients taking bronchial asthma drugs, including montelukast; this is an indication for the use of systemic glucocorticosteroids. Such cases are usually, but not always, associated with dose reduction or withdrawal of oral glucocorticosteroids. The possibility that administration of leukotriene receptor antagonists may be associated with the occurrence of Churg-Strauss syndrome cannot be excluded or confirmed. Physicians should be advised of the possibility of eosinophilia, vasculitic rash, increased pulmonary symptoms, cardiac and/or neuropathic complications in their patients. Patients with the above symptoms should be re-examined and their treatment regimen should be revised.
Administration during pregnancy and lactation
The drug may be used during pregnancy and lactation if the expected benefits to the mother exceed the potential risk to the fetus and child.
Effect of the drug on ability to drive vehicles and mechanisms
It is assumed that the drug does not affect the ability to drive vehicles or operate other mechanisms. However, in very rare cases, somnolence has been marked in patients.
Symptoms: abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity.
Treatment: symptomatic. It is not known whether montelukast is excreted by peritoneal dialysis or hemodialysis.
Form of release
10 mg film-coated tablets in a carton pack.
In a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children!
3 years. Do not use after the expiration date.
Conditions of dispensing from pharmacies
Released by a doctor’s prescription.