Ipraterol-aeronativ aerosol for inhalation, aerosol can of 200 doses, 20mcg/dose + 50mcg/dose

Composition

aerosol for inhalation dosed.

Composition for 1 dose:

Active ingredients:

Ipratropium bromide monohydrate (based on ipratropium bromide) 0.021 mg (0.020 mg)

Fenoterol hydrobromide 0.050 mg

Auxiliary substances:

Absolute ethanol 15,300 mg

Citric acid monohydrate 0.005 mg

Triethyl Citrate 0.150 mg

Propellant R 134 a (1,1,1,2-tetrafluoroethane) 44,470 m

Pharmacological action

Pharmacotherapeutic group: combined bronchodilator (beta_-2-adrenomimetic selective + m-holinoblokator).

ATX code: R03AL01

Pharmacological properties

Pharmacodynamics

The drug Ipraterol-aeronative contains two components with 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 (parasympatholytic) 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 disease (chronic bronchitis and emphysema), significant improvements in lung function (increase in forced expiratory volume in 1 second (FEV₁) and peak expiratory flow (PSV) by 15% or more) is celebrated for 15 minutes, the maximum effect is reached after 1-2 hours and lasts in the majority of patients up to 6 hours after injection.

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. Stimulation of β1-adrenergic receptors activates adenylate cyclase through stimulation of Gsprotein. Beta_-1-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 application, 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 is noted.

the beta_-2-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 a prolongation of the QT interval_with the use of 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 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 phenomenon has not been clarified. Tremor is the most common adverse effect when using beta-adrenergic agonists. With the combined use of these two active substances, the bronchodilator effect of the drug.

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

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.

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

Depending on the method of inhalation and the inhalation system used, about 10-30% of the Active ingredient reaches the lower respiratory tract, and the rest 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 (T_1/2) of 11 minutes, and 70% is absorbed slowly with T_1/2-120 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 the Active ingredient 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 the fact that the ingested amount of the drug has virtually no effect on the concentration of the Active ingredient in the blood plasma achieved 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 is 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

: Chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchial asthma (mild to moderate severity).

Use during pregnancy and lactation

Data from preclinical studies and existing clinical experience with the use of a combination of fenoterol and ipratropium bromide have shown that the active substances included in the combined drug do not have a negative effect during pregnancy. The possibility of an inhibitory effect of fenoterol on uterine contractility should be considered. The drugIpraterol-aeronative is contraindicated in the first trimester of pregnancy (possible weakening of labor). Ipraterol-aeronative should be used with caution in the second and third trimesters of pregnancy.

Fenoterol passes into breast milk. Data confirming that ipratropium bromide penetrates into breast milk have not been obtained. The safety of using the drug during breastfeeding has not been established. In this regard, the use of the drugIpraterol-aeronative during breastfeeding is possible only if the potential benefit to the mother exceeds the potential risk to the child.

Contraindications

: Hypertrophic obstructive cardiomyopathy.

– Tachyarrhythmia.

– First trimester of pregnancy.

– Children under 6 years of age.

With caution

The drugIpatrol-aeronatic should be used with caution in patients with diseases such as angle-closure glaucoma, hypertension, diabetes, recent myocardial infarction (within the last 3 months), disease of the heart and blood vessels such as congestive heart failure, ischemic heart disease, arrhythmias, aortic stenosis, severe lesions of the cerebral and peripheral arteries, hyperthyroidism, pheochromocytoma, benign prostate hyperplasia, obstruction of the bladder neck, cystic fibrosis, II and III trimesters of pregnancy, the period of breastfeeding. Ipraterol-aeronative should be used with caution in children and adolescents aged 6 to 18 years.

Side effects

Many of these undesirable effects may be due to the anticholinergic and beta-adrenergic properties of the drugIpraterol is an aeronative. Application of the drugIpraterol-aeronative, like any inhalation therapy, can cause local irritation.

Frequency detection: very common (>1/10), common (1/100 to 1/10), infrequent (1/1000 to 1/100), rare (1/10000 to 1/1000), very rare (><1/10000), (including individual messages).

Immune system disorders: rarely-hypersensitivity reactions, anaphylactic reactions (angioedema).

Metabolic and nutritional disorders: rarely-hypokalemia.

Mental disorders: infrequently-nervousness; rarely – feelings of anxiety, mental disorders (mental disorders).

Nervous system disorders: infrequently-headache, dizziness, tremor.

Visual disorders: rarely-glaucoma, increased intraocular pressure, accommodation disorders, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, the appearance of a halo around objects and colored spots in front of the eyes.

Cardiac disorders: infrequently-tachycardia, palpitation sensation; rarely-arrhythmia, atrial fibrillation, supraventricular tachycardia, myocardial ischemia.

Respiratory, thoracic and mediastinal disorders: often-cough; infrequently-pharyngitis, dysphonia; rarely-bronchospasm, pharyngeal irritation, pharyngeal edema, laryngospasm, paradoxical bronchospasm, dry throat.

Gastrointestinal disorders: infrequently-vomiting, dry mouth, nausea; rarely-stomatitis, glossitis, gastrointestinal motility disorders, diarrhea, constipation, oral edema.

Skin and subcutaneous tissue disorders: rarely-urticaria, skin rash, itching, sweating.

Musculoskeletal and connective tissue disorders: rarely-muscle weakness, myalgia( muscle pain), muscle spasm.

Renal and urinary tract disorders: rarely-urinary retention.

Laboratory and instrumental data: infrequently-increased systolic blood pressure; rarely-increased or decreased diastolic blood pressure.

If any of the side effects listed in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Long-term concomitant use of Ipraterol-aeronative with other anticholinergic drugs is not recommended due to the lack of data.

Concomitant use of other beta-adrenomimetic and anticholinergic drugs, including systemic action, and xanthine derivatives (for example, theophylline) may increase the bronchodilator effect of the drugIpraterol is an aeronative and may lead to increased adverse reactions.

There may be a significant weakening of the bronchodilator effect of the drugIpraterol is an aeronative with simultaneous use of beta-blockers.

Hypokalemia associated with the use of beta-adrenomimetics may be increased by concomitant 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.

Patients receiving monoamine oxidase inhibitors and tricyclic antidepressants should be given beta-2-adrenergic medications with caution, as these medications may 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, two 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 the effect is absent after 4 inhaled doses, and additional inhalations are required, you should immediately seek medical attention.

Intermittent and long-term therapy-1-2 inhalations at a 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 Ipraterol-aeronative in children should be used only as prescribed by a doctor and under the supervision of adults (see the section “Special instructions”). Inhalation instructions Patients should be instructed about the correct use of metered-dose aerosol. Ipraterol-aeronative is intended for inhalation use only. Before using the inhaler for the first time, or if the inhaler has not been used for a week or longer, check its operation. To do this, remove the protective cap from the mouthpiece of the inhaler, shake the inhaler well and press the cylinder, releasing one stream of the drug into the air. Performing inhalation Step 1. Remove the protective cap from the mouthpiece of the inhaler as shown in Figure 1. Step 2. Shake the inhaler vigorously. Step 3. Take a slow, full exhalation. Do not exhale into the inhaler!Step 4. While holding the balloon as shown in Figure 2, wrap your lips tightly around the mouthpiece. The balloon must be pointed upside down!Step 5. Inhale as deeply as possible, while quickly pressing the bottom of the balloon until one inhaled dose is released. Step 6. Hold your breath for a few seconds, then remove the mouthpiece from your mouth and slowly exhale through your nose.

Step 7. Put the protective cap on the mouthpiece of the inhaler. Repeat steps 2-6 for a second inhaled dose, if necessary. Cleaning the inhaler Regularly (once a week), flush the mouthpiece of the inhaler as shown in Figure 3. Remove the metal canister from the plastic case and rinse the bottle and cap with warm water. Do not use hot water. Dry thoroughly, but do not use heating devices for this purpose. Put the can back in its case and put the cap back on. Do not immerse the metal canister in water.

Overdose

Symptoms

Symptoms of overdose are usually associated with the action of fenoterol. Symptoms may occur due to excessive stimulation of beta-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

It is necessary to stop taking the drug Ipraterol-aeronative. 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, beta-blockers may be used, 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.

Description

Colorless or slightly yellowish transparent solution, under pressure, in a stainless steel cylinder with a metering valve and a spray nozzle; the preparation is sprayed as an aerosol jet when leaving the cylinder.

Special instructions

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

In children, the drugIpraterol-aeronative should only be used as prescribed by a doctor and under adult supervision. Use in children under 6 years of age is contraindicated, due to the lack of experience of use.

Hypersensitivity

After the use of Ipraterol-aeronative, immediate hypersensitivity reactions may occur, which in rare cases may include: urticaria, angioedema, rash, bronchospasm, oropharyngeal edema, anaphylactic shock.

Paradoxical bronchospasm

The drugIpraterol-aeronative, like other inhaled medications, can cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm develops, the use of Ipraterol-aeronative should be stopped immediately and alternative therapy should be switched.

Long-term use

– in patients with bronchial asthma drugIpraterol-aeronative should be used only as needed; in patients with mild COPD, symptomatic treatment may be preferable to regular use;

– in patients with bronchial asthma, it should be remembered that anti-inflammatory therapy should be carried out or enhanced 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 the drugIpraterol is anaeronative used to relieve bronchial obstruction, which can cause an uncontrolled worsening of the course of the disease. In case of increased bronchial obstruction, increase the dose of beta_-2-adrenomimetics, including the drugIpraterol is anaeronative, more than the recommended amount 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 simultaneously with Ipraterol-aeronative only under medical supervision.

Disorders of the gastrointestinal tract

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

Visual disturbances

The drugIpraterol-aeronative 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 about the correct use of the inhaled drug. Ipraterol is an aeronative. To prevent the solution from getting into the eyes, it is recommended that the solution used with the nebulizer be inhaled through the mouthpiece. In the absence

of a mouthpiece, a face mask that fits snugly should be used. 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), the drug is used to treat the following diseases:Ipraterol aeronative 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 diseases (for example, coronary heart disease, arrhythmias, or severe heart failure) receiving the drugIpraterol is anaeronative, you should be warned about the need to consult a doctor in case of pain in the heart or other symptoms that indicate a worsening of heart disease. It is necessary to pay attention to symptoms such 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”).

In athletes, the use of the drugIpraterol-aeronative due to the presence of fenoterol in its composition can lead to positive results of doping tests.

Influence on the ability to drive vehicles and mechanisms

Studies of the effect of a combined preparation containing ipratropium bromide and fenoterol on the ability to drive vehicles and mechanisms have not been conducted. Since the use of the drug may lead to the development of such adverse reactions as dizziness, nervousness, tremor, impaired eye accommodation, mydriasis and blurred vision, caution should be exercised when driving vehicles and mechanisms, as well as when engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Aerosol for inhalation dosed,20 mcg / dose + 50 mcg / dose.

200 doses of the drug in a stainless steel cylinder with a metering valve and a spray nozzle. Each cylinder together with the instructions for use in a cardboard pack.

Storage conditions

In a place protected from light at a temperature not exceeding 25 °C, away from heating devices. Do not freeze it. 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

Purpose

Adults as prescribed by a doctor, Nursing mothers, Pregnant women as prescribed by a doctor, Children as prescribed by a doctor

Indications

Bronchial Asthma, Low Learning Rate, Bronchospasm