Astmasol Neo inhalation aerosol metered dose 20 µg/dose+50 µg/dose, 200 doses

Composition

Per 1 dose of active substances: Ipratropium bromide monohydrate 0.021 mg, in terms of ipratropium bromide 0.020 mgfenoterol hydrobromide 0.050 MGM Auxiliary substances: Ethanol anhydrous (absolute ethyl alcohol) 13.313 mg Water for injection 0.799 mg Citric acid anhydrous 0.001 mg Propellant HFA-134a (1,1,1,2-tetrafluoroethane) 39.070 mg

Pharmacological action

Combined bronchodilator (m-holinoblokator + beta-2-adrenomimetic selective)

ATX code: R03AL01

Pharmacological properties

Pharmacodynamics

The drug contains two components that have bronchodilatory activity: ipratropium bromide-m-holinoblokator and fenoterol-β2-adrenomimetic.

Bronchodilation during inhaled use of ipratropium bromide is mainly due to local, rather than systemic, anticholinergic effects.

Ipratropium bromide is a quaternary ammonium derivative with anticholinergic (parasympatholic) properties. Ipratropia bromide inhibits reflexes caused by the vagus nerve. Anticholinergic agents prevent an increase in the intracellular concentration of calcium ions, which occurs due to the interaction of acetylcholine with muscarinic receptors of the smooth muscles of the bronchi. The release of calcium ions is mediated by a system of secondary mediators, including inositol triphosphate (ITP) and diacylglycerol (DAG).

In patients with bronchospasm associated with chronic obstructive pulmonary diseases (chronic bronchitis and emphysema), a significant improvement in lung function (an increase in forced expiratory volume in 1 second (OOB1) and peak expiratory velocity (PEP) by 15% or more) is noted within 15 minutes, the maximum effect is achieved in 1-2 hours and lasts in most patients up to 6 hours after use.

Ipratropium bromide does not adversely affect mucus secretion in the respiratory tract, mucociliary clearance and gas exchange.

Fenoterol selectively stimulates beta-2-adrenergic receptors at a therapeutic dose.

Beta-2-adrenergic receptors are stimulated at high doses.

Fenoterol relaxes the smooth muscles of the bronchi and blood vessels and counteracts the development of bronchospastic reactions caused by the influence of histamine, methacholine, cold air and allergens (immediate hypersensitivity reactions).

Immediately after use, fenoterol blocks the release of inflammatory mediators and bronchial obstruction from mast cells. In addition, when using fenoterol in doses of 0.6 mg, an increase in mucociliary clearance was noted.

beta-adrenergic (beta-adrenergic stimulating) effect of the drug on cardiac activity, such as an increase in the frequency and strength of heart contractions, is due to the vascular effect of fenoterol, stimulation of beta-2-adrenergic receptors of the heart, and when using doses higher than therapeutic, stimulation of beta-1-adrenergic receptors.

As with the use of other beta-adrenergic drugs, there is an elongation of the QTC interval when using high doses. When using fenoterol with metered-dose aerosol inhalers (DAI), this effect was not constant and was observed in the case of doses exceeding the recommended ones.

However, after using fenoterol with nebulizers (a solution for inhalation in vials or dropper tubes with a standard dose), the systemic effect may be higher than when using the drug with DAI in the recommended doses. The clinical significance of these observations has not been established. The most commonly observed effect of beta-adrenergic agonists is tremor. In contrast to the effect on the smooth muscles of the bronchi, tolerance can develop to the systemic effects of beta-adrenergic agonists, the clinical significance of this manifestation has not been clarified.

Tremor is the most common adverse effect when using beta-adrenergic agonists. When these two active substances are used together, the bronchodilator effect is achieved by acting on various pharmacological targets. These substances complement each other, as a result, the antispasmodic effect on the bronchial muscles increases and a greater breadth of therapeutic action is provided for bronchopulmonary diseases accompanied by airway constriction.

The complementary effect is such that to achieve the desired effect, a lower dose of the beta-adrenergic component is required, which allows you to individually select the effective dose with the practical absence of side effects.

In acute bronchoconstriction, the effect of the drug develops quickly, which allows it to be used in acute attacks of bronchospasm.

Pharmacokinetics

There is no evidence that the pharmacokinetics of the combined preparation containing ipratropium bromide and fenoterol differ from those of each of the individual components.

Suction

Ipratropium bromide. With the inhaled route of use, ipratropium bromide is characterized by extremely low absorption from the respiratory mucosa.

The concentration of ipratropium bromide in blood plasma is at the lower limit of determination, and it can be measured only when using high doses of the Active ingredient. After inhalation,10-30% of the administered dose of ipratropium bromide usually enters the lungs (depending on the dosage form and method of inhalation). Most of the dose is swallowed and enters the gastrointestinal tract.

A portion of the ipratropium bromide dose that enters the lungs quickly reaches the systemic circulation (within a few minutes). The total systemic bioavailability of ipratropium bromide administered orally and by inhalation is 2% and 7-28%, respectively.

Fenoterol.

Depending on the method of inhalation and the inhalation system used, about 10-30% of fenoterol reaches the lower respiratory tract, and the remainder is deposited in the upper respiratory tract and swallowed. As a result, a certain amount of inhaled fenoterol enters the gastrointestinal tract.

Absorption is biphasic – 30% of fenoterol is rapidly absorbed with a half-life (half-life) of 11 minutes, and 70% is absorbed slowly with a half-life of 120 minutes. There is no correlation between the plasma concentrations of fenoterol achieved after inhalation and the pharmacodynamic time-effect curve. The long-term (3-5 hours) bronchodilator effect of the drug after inhalation, comparable to the corresponding effect achieved after intravenous use, is not supported by high concentrations of fenoterol in the systemic circulation. After oral use, about 60% of fenoterol is absorbed. The time to reach the maximum concentration in blood plasma is 2 hours.

Distribution

Ipratropium bromide, which is a quaternary amine, is poorly soluble in fats and weakly penetrates biological membranes. It doesn’t accumulate. Ipratropium bromide binds to plasma proteins to a minimal extent (less than 20%). There are no data on the possibility of penetration of ipratropium bromide through the placental barrier and into breast milk.

Fenoterol is intensively distributed to organs and tissues. Binding to plasma proteins is 40-55%. Fenoterol in unchanged form penetrates the placental barrier and is excreted in breast milk.

Metabolism

Ipratropium bromide is metabolized by oxidation mainly in the liver. Up to 8 metabolites of ipratropium bromide are known to bind weakly to muscarinic receptors and are considered inactive.

Fenoterol is metabolized in the liver. After 24 hours,60% of the intravenous dose and 35% of the oral dose are excreted in the urine. This proportion of fenoterol undergoes biotransformation due to the effect of “primary passage” through the liver, as a result of which the bioavailability of the drug after oral use decreases to approximately 1.5%. This explains why. that the ingested amount of the drug has practically no effect on the concentration of the Active ingredient in the blood plasma reached after inhalation. Biotransformation of fenoterol in humans occurs mainly by conjugation with sulfates in the intestinal wall.

Deduction

Ipratropia bromide is mainly excreted through the intestines, as well as through the kidneys. About 25% is excreted unchanged, the rest in the form of metabolites.

Fenoterol is excreted by the kidneys and bile in the form of inactive sulfate conjugates.

When parenterally administered, fenoterol is excreted in a three – phase model with half-lives of 0.42 minutes,14.3 minutes and 3.2 hours, respectively.

Pharmacokinetics in individual groups of patients

The pharmacokinetics of the combined drug containing ipratropium bromide and fenoterol in patients with diabetes mellitus, elderly and older patients, children, as well as in patients with impaired liver and kidney function have not been studied.

Indications

Prevention and symptomatic treatment of obstructive airway diseases with reversible airway obstruction: chronic obstructive pulmonary disease (COPD), bronchial asthma, and chronic bronchitis complicated or uncomplicated by emphysema.

Use during pregnancy and lactation

Pregnancyexisting clinical experience has shown that fenoterol and ipratropium do not have a negative effect on pregnancy. However, when using these medications during pregnancy, the usual precautions should be followed, especially in the first trimester. The inhibitory effect of fenoterol on uterine contractility should be taken into account. Breast-feeding periodoclinical studies have shown that fenoterol hydrobromide can enter breast milk. No such data were obtained for ipratropium.A significant effect of ipratropium on an infant, especially in the case of using the drug in the form of an aerosol, is unlikely. However, given the ability of many medications to pass into breast milk, when prescribing Astmasol® neo women who are breast-feeding should exercise caution.

Contraindications

Hypertrophic obstructive cardiomyopathy, tachyarrhythmia, hypersensitivity to fenoterol hydrobromide, atropine-like substances or any other components of the drug. 1st trimester of pregnancy, children under 6 years of age. With caution

The drug should be used with caution in patients with diseases such as angle-closure glaucoma, coronary insufficiency, arterial hypertension, insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart and vascular diseases, hyperthyroidism, pheochromocytoma, prostatic hypertrophy, bladder neck obstruction, cystic fibrosis, and childhood.

Side effects

Many of these undesirable effects may be due to the anticholinergic and beta-adrenergic properties of the drug. The use of Astmasol ® neo, like any inhalation therapy, may cause local irritation. The most common side effects reported in clinical trials were cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, increased systolic blood pressure, and nervousness. The frequency of adverse reactions that may occur during therapy was determined in accordance with the recommendations of the World Health Organization: very common (>1/10), often (>>1/100, >><1/10), infrequently (>1/1000, <1/10), infrequently (><1/100), rarely (>1/10000, <1/100), rarely (><1/1000), very rarely (Immune system disorders. Rare: anaphylactic reaction, hypersensitivity.

Metabolic and nutritional disorders. Rare: hypokalemia.

Mental disorders. Infrequently: nervousness. Rarely: agitation, mental disorders.

Nervous system disorders. Infrequently: headache, tremor, dizziness.

Visual disturbances. Rare: glaucoma, increased intraocular pressure, accommodation disorders, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, ghosting around objects.

Disorders of the cardiovascular system. Infrequently: increased heart rate, tachycardia, palpitation sensation. Rare: arrhythmia, atrial fibrillation, supraventricular tachycardia, myocardial ischemia.

Respiratory, thoracic, and mediastinal disorders. Often: cough. Infrequently: pharyngitis, dysphonia. Rare: bronchospasm, pharyngeal irritation, pharyngeal edema, laryngospasm, paradoxical bronchospasm, dry throat.

Disorders of the gastrointestinal tract. Infrequently: vomiting, nausea, dry mouth. Rare: stomatitis, glossitis, gastrointestinal motility disorders, diarrhea, constipation, oral edema.

Skin and subcutaneous tissue disorders. Rare: urticaria, pruritus, rash, angioedema, hyperhidrosis.

Musculoskeletal and connective tissue disorders. Rare: muscle weakness, muscle spasms, myalgia.

Disorders of the kidneys and urinary tract. Rare: urinary retention.

Laboratory and instrumental data. Infrequently: increased systolic blood pressure. Rarely: increased diastolic blood pressure.

Interaction

Long-term concomitant use of the drug with other angicholinergic drugs is not recommended due to the lack of data. Concomitant use of other beta-adrenomimetic and anticholinergic drugs, including systemic ones, and xanthine derivatives (for example, theophylline) may increase the bronchodilator effect of the drug and lead to increased adverse reactions. It is possible to significantly weaken the bronchodilator effect of the drug with simultaneous use of beta-blockers. Hypokalemia associated with the use of beta-adrenomimetics. It can be enhanced by simultaneous use of xanthine derivatives, glucocorticosteroids and diuretics. This fact should be given special attention in the treatment of patients with severe obstructive airway diseases. Hypokalemia may lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia can increase the negative effect of hypokalemia on the heart rate. In such cases, it is recommended to monitor the concentration of potassium in the blood plasma. Beta-2-adrenergic drugs should be used with caution in patients who have received monoamine oxidase inhibitors and tricyclic antidepressants, as these drugs can enhance the effect of beta-adrenergic agents. Inhalation of general anaesthetic agents, such as halogenated hydrocarbon anaesthetics (halothane, trichloroethylene, enflurane), may increase the adverse effects of beta-adrenergic agents on the cardiovascular system. The combined use of the drug with Cromoglicic acid and / or glucocorticosteroids increases the effectiveness of therapy

How to take, course of use and dosage

The dose should be selected individually. In the absence of other instructions from the doctor, the following doses are recommended::Adults and children over 6 years of age

Treatment of seizures

In most cases,2 inhaled doses of aerosol are sufficient to relieve symptoms. If there is no relief of breathing within 5 minutes, you can use an additional 2 inhaled doses.

If there is no effect after 4 inhaled doses and additional inhalations are required, you should immediately seek medical attention.

Intermittent and long-term therapy

1-2 inhalations at one time, up to 8 inhalations per day (on average,1-2 inhalations 3 times a day). For bronchial asthma, the drug should only be used as needed.

The drug in children should be used only as prescribed by a doctor and under the supervision of adults.

Overdose

Symptoms of overdose are usually associated with the action of fenoterol. Symptoms may occur due to excessive stimulation (3-adrenergic receptors. Most likely to occur are tachycardia, palpitations, tremors, hypertension or hypotension, an increase in the difference between systolic and diastolic blood pressure, an increase in pulse pressure, increased angina pain, arrhythmia and a feeling of” hot flashes ” of blood to the face, metabolic acidosis, hypokalemia, a feeling of heaviness behind the sternum, and increased bronchial obstruction. Possible symptoms of an overdose of ipratropium bromide (such as dry mouth, impaired eye accommodation), given the wide range of therapeutic effects of the drug and the local method of application, are usually mild and transient. Treatment: You should stop taking the drug. It is necessary to take into account the data of monitoring the acid-base balance of the blood. It is recommended to prescribe sedatives, anxiolytic drugs (tranquilizers), in severe cases – intensive care. As a specific antidote, it is possible to use (beta-blockers, preferably selective beta-1-blockers. However, one should be aware of the possible increase in bronchial obstruction under the influence of beta-blockers and carefully select the dose for patients with bronchial asthma or chronic obstructive pulmonary disease due to the risk of developing severe bronchospasm, which can lead to death.

Special instructions

Shortness of breath

In case of sudden rapid increase in shortness of breath (difficulty breathing), you should immediately consult a doctor.

Children

In children, the drug Astmasol® neo should only be tried on when prescribed by a doctor and under adult supervision. Use in children under 6 years of age is contraindicated due to lack of experience.

Hypersensitivity

After using Astmasol® neo immediate hypersensitivity reactions may occur, which in rare cases may include: urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, anaphylactic shock.

Paradoxical bronchospasm

Astmasol ® neo, like other inhaled medications, can cause paradoxical bronchospasm, which can be life-threatening. In case of development of paradoxical bronchospasm, the use of Astmasol® neo should be stopped immediately and switched to alternative therapy.

Long-term use

In patients with bronchial asthma, the drug should only be used as needed. In patients with mild COPD, symptomatic treatment may be preferable to regular use.

Patients suffering from bronchial asthma should be aware of the need to conduct or strengthen anti-inflammatory therapy to control the inflammatory process of the respiratory tract and the course of the disease.

Regular use of increasing doses of drugs containing beta-2-adrenomimetics, such as Astmasol ® neo, to relieve bronchial obstruction may cause uncontrolled worsening of the course of the disease. In case of increased bronchial obstruction, increase the dose of beta-2-adrenomimetics. including the drug Astmasol ® neo, more than recommended for a long time is not only not justified, but also dangerous. To prevent a life-threatening worsening of the course of the disease, consideration should be given to reviewing the patient’s treatment plan and adequate anti-inflammatory therapy with inhaled glucocorticosteroids.

Other sympathomimetic bronchodilators should be administered concomitantly with Astmasol neo is only under medical supervision.

Disorders of the gastrointestinal tract

Patients with a history of cystic fibrosis may have gastrointestinal motility disorders.

Visual disturbances

The drug Astmasol® neo should be used with caution in patients predisposed to angle-closure glaucoma. There have been isolated reports of visual complications (e. g., increased intraocular pressure, mydriasis, angle-closure glaucoma, eye pain) that developed when inhaled ipratropium bromide (or ipratropium bromide in combination with beta-2-adrenomimetics) got into the eyes.

Symptoms of acute angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo around objects and colored spots in front of the eyes, combined with corneal edema and redness of the eyes due to conjunctival hyperemia. If any combination of these symptoms develops, the use of eye drops that reduce intraocular pressure is indicated, and immediate consultation with a specialist.

Patients should be instructed on the correct use of the inhaled drug Astmasol ® neo. Patients predisposed to developing glaucoma should take special care to protect their eyes.

System effects

For diseases such as recent myocardial infarction, diabetes mellitus with inadequate glycemic control, severe organic heart and vascular diseases, hyperthyroidism, pheochromocytoma, or obstruction of the urethra (for example, prostatic hyperplasia or bladder neck obstruction), Astmasol®is indicated for the treatment of: neo should only be used after a thorough risk / benefit assessment, especially when using doses higher than recommended.

Impact on the cardiovascular system

There have been rare cases of myocardial ischemia when taking beta-2-adrenomimetics. Patients with concomitant serious heart conditions (for example, coronary heart disease, arrhythmias, or severe heart failure) receiving Astmasol ® neo should be warned about the need to consult a doctor if they experience heart pain or other symptoms that indicate a worsening of heart disease. It is necessary to pay attention to such symptoms as shortness of breath and chest pain, as they can be both cardiac and pulmonary etiology.

Hypokalemia

Hypokalemia may occur when beta-2-adrenomimetics are used (see section “Overdose”). Use of Astmasol®in athletes neo due to the presence of fenoterol in its composition can lead to positive results of doping tests. It should be noted that the drug contains a small amount of ethanol (13.313 mg in one dose).

Influence on the ability to drive vehicles and mechanisms

Studies on the effect of the drug on the ability to drive vehicles and mechanisms have not been conducted. Caution should be exercised when performing these activities, as dizziness, tremor, eye accommodation disorders, mydriasis, and blurred vision may develop. If you experience the above undesirable sensations, you should refrain from such potentially dangerous actions as driving vehicles and mechanisms.

Storage conditions

At a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date!

Active ingredient

Ipratropium bromide, Fenoterol

Conditions of release from pharmacies

By prescription

Dosage form

aerosol for inhalation