Ipraterol aeronautive - instructions for use, dose, side effects, contraindications

Active substanceIpratropium bromide + FenoterolIpratropium bromide + Fenoterol

Similar drugsTo uncover

Berodual®

solution d / inhal.

Boehringer Ingelheim International GmbH Germany

Berodual® H

aerosol d / inhal.

Boehringer Ingelheim International GmbH Germany

Inspiration®

aerosol d / inhal.

BINNOFARM, CJSC Russia

Iperate aeronaut

aerosol d / inhal.

NATIVA, LLC Russia

Ipraterol-native

solution d / inhal.

NATIVA, LLC Russia

Dosage form: & nbsp

aerosol for inhalation dosed

Composition:

Composition per 1 dose:

Active substances:

Ipratropium bromide monohydrate 0.021 mg

(in terms of ipratropium bromide) (0.020 mg)

Fenoterol hydrobromide 0.050 mg

Excipients:

Ethanol is absolute 15.300 mg

Citric acid monohydrate 0.005 mg

Triethyl citrate 0.150 mg

Propellant R 134a (1,1,1,2-tetrafluoroethane) 44.470 mg

Description:Colorless or with a slight yellowish tinge, a clear, pressurized solution in a stainless steel container with a dosing valve and a spray nozzle; The drug is sprayed out of the balloon as an aerosol spray.

Pharmacotherapeutic group:Bronchodilator combined (β2-adrenomimetic selective + m-holinoblokator)

ATX: & nbsp

R.03.A.L.01 Fenoterol and ipratropium bromide

Pharmacodynamics:

Iperate aeronaut contains two components that have broncholytic activity: ipratropium bromide - m-holinoblokator and fenoterol - β₂-adrenomimetic. Bronchodilation in the inhalation of ipratropium bromide is mainly due to local, rather than systemic, anticholinergic action.

Pharmacodynamics

Ipratropium bromide is a quaternary ammonium derivative possessing anticholinergic (parasympatolytic) properties. Ipratropium bromide inhibits the reflexes caused by the vagus nerve. Anticholinergic drugs prevent the increase in the intracellular concentration of calcium ions, which occurs due to the interaction of acetylcholine with muscarinic receptors of smooth muscles of the bronchi. The release of calcium ions is mediated by a system of secondary mediators, which include ITF (inositol triphosphate) and DAG (diacylglycerin).

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

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

Fenoterol selectively stimulates β₂-adrenoceptors in a therapeutic dose. Stimulation of β₁-adrenoceptors occurs when high doses are used. This explains the β-adrsnergic (stimulating β-adrenoreceptors) effect of the drug on cardiac activity, such as increased frequency and strength of heartbeats, lengthening of the interval QT_FROM.

Fenoterol relaxes the smooth musculature of the bronchi and vessels and counteracts the development of bronchospastic reactions due to the influence of histamine, methacholine, cold air and allergens (immediate-type hypersensitivity reactions). Immediately after the introduction fenoterol blocks the release of mediators of inflammation and bronchoobstruction from mast cells. In addition, when fenoterol was used at higher doses, there was an increase in mucociliary clearance.

When using fenoterol with metered-dose aerosol inhalers (DAS), systemic effects are noted when doses exceeding recommended levels are used. However, after the use of fenoterol with nebulizers (solution for inhalation in vials with a standard dose), systemic exposure may be higher than with the use of the drug with the help of DAD in the recommended doses. The clinical significance of these observations is not established. The most frequently observed effect of β-adrenoreceptor agonists (β₂-adrenomimetikov) is a tremor. Unlike the effects on the smooth muscles of the bronchi, the systemic effects of β-adrenoreceptor agonists may develop tolerance, but the clinical significance of this manifestation is not clear.

In the joint application of ipratropium bromide and fenoterol bronchodilating (bronchodilator) effect is achieved by affecting various pharmacological targets. These substances complement each other, as a result of increased spasmolytic effect on the muscles of the bronchi and provides a great breadth of therapeutic effect for bronchopulmonary diseases, accompanied by airway obstruction.Complementary action is such that to achieve the desired effect, a lower dose of β-adrenergic component is required, which allows individual selection of an effective dose with almost no side effects.

Pharmacokinetics:

There is no evidence that the pharmacokinetics of the combination drug

differs from that of each of the individual components.

Suction

Ipratropium bromide. After inhalation into the lungs, 10-30% of the administered dose of the drug usually falls (depending on the dosage form and inhalation method). Most of the dose is swallowed and enters the gastrointestinal tract. Part of the dose of the drug, which enters the lungs, quickly reaches the systemic blood flow (within a few minutes).

The total systemic bioavailability of ipratropium bromide, used by inhalation, is 7-28%.

Fenoterol. Depending on the inhalation method and the inhalation system used, about 10-30% of the active substance reaches the lower respiratory tract, and the remainder is deposited in the upper respiratory tract and swallowed. As a result, some amount of inhaled fenoterol enters the gastrointestinal tract.Absorption is biphasic in nature - 30% of fenoterol is rapidly absorbed with a half-life (T_1/2) 11 minutes, and 70% is absorbed slowly from T_1/2- 120 minutes. There is no correlation between the concentrations of fenoterol in the blood plasma, we reach 1.1 after the inhalation, and the pharmacodynamic "time-effect" curve. The prolonged (3-5 hours) bronchodilatory effect of the drug after inhalation, comparable to the corresponding effect achieved after intravenous administration, is not supported by high concentrations of active substance in the systemic circulation.

Distribution

Ipratropium bromide. There is a rapid two-phase decrease in plasma concentration. The apparent volume of distribution during the state of equilibrium concentration (Css) is approximately 176 L 2.4 L / kg). Ipratropium bromide binds to plasma proteins to a minimum degree (less than 20%).

Ipratropium bromide, which is a quaternary amine, does not penetrate the blood-brain barrier. There is no data on the possible penetration of ipratropium bromide through the placental barrier and into breast milk. Do not cumulate.

Fenoterol. Fenoterol intensively distributed to organs and tissues.The apparent volume of distribution during the state of equilibrium concentration is approximately 189 liters (ᴝ2.7 l / kg). Relationship with plasma proteins 40-55%. Fenoterol in unchanged form penetrates the placental barrier and is excreted in breast milk.

Metabolism

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

Fenoterol. Metabolised in the liver. If swallowed fenoterol is biotransformation due to the effect of "primary transmission" through the liver. The swallowed amount of the drug has no effect on the concentration of the active substance in the blood plasma, achieved after inhalation. Biotransformation of fenoterol in humans occurs by conjugation with glucuronides and sulfates. After oral administration fenoterol is metabolized predominantly by sulfation in the intestinal wall.

Excretion

Ipratropium bromide. It is excreted primarily through the intestines, as well as through the kidneys. About 25% is excreted unchanged, the rest - in the form of metabolites.

Fenoterol. Biotransformation, including excretion with bile, undergoes the bulk of fenoterol - approximately 85%.

The excretion of fenoterol with urine (0.27 L / min) corresponds to approximately 15% of the average total clearance of the systemically available dose. The volume of renal clearance testifies to the tubular secretion of fenoterol in addition to glomerular filtration. After inhalation of the metered aerosol in unchanged form, 2% of the dose is released through the kidneys within 24 hours.

Pharmacokinetics in various groups.

The pharmacokinetics of the combination of ipratropium bromide and fenoterol in patients with diabetes mellitus has not been studied.

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

Contraindications:

- Hypersensitivity to fenoterol, ipratropium bromide (and also to other atropine-like drugs) and the auxiliary components that make up the drug.

- Hypertrophic obstructive cardiomyopathy.

- Tachyarrhythmia.

- The first trimester of pregnancy.

- Children under 6 years.

Carefully:

Iperate aeronaut should be used with caution in patients with diseases such as angle-closure glaucoma, chronic heart failure, ischemic heart disease, arrhythmias, aortic stenosis, hypertension, insufficiently controlled diabetes mellitus, recent myocardial infarction (within the last 3 months), severe organic heart disease and vessels, hyperthyroidism, pheochromocytoma, prostatic hyperplasia, obstruction of the bladder neck, cystic fibrosis.

A drug Iperate aeronaut should be used with caution in children and adolescents aged 6 to 18 years.

Pregnancy and lactation:

The existing clinical experience has shown that fenoterol and ipratropium bromide do not have a negative effect on pregnancy. Nevertheless, when using these drugs during pregnancy (second and third trimester), the usual precautions should be observed.

It is necessary to take into account the inhibitory effect of the preparation Iprateol-aeronative on uterine contractility.

Fenoterol penetrates into breast milk.With respect to ipratropium bromide, such data are not obtained. The safety of the drug during lactation is not established. In this regard, the use of the drug Ipateol aeronauts during lactation is possible only in cases where the potential benefit to the mother exceeds the potential risk for the child.

Dosing and Administration:

The dose should be selected individually.

In the absence of other instructions from a doctor, the following doses are recommended:

Adults and children over 6 years of age:

Treatment of attacks

In most cases, two inhalation doses of aerosol are sufficient to stop the symptoms. If no breathing has occurred within 5 minutes, an additional 2 inhalation doses may be used. If the effect is absent after 4 inhalation doses and additional inhalations are required, seek medical help immediately.

Intermittent and prolonged therapy:

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

Iperate aeronaut should be used in children only as directed by a doctor and under the supervision of adults (see section "Special instructions").

Instructions for inhalation

Patients should be instructed about the correct use of the metered aerosol.

Iperate aeronaut is only for inhalation use.

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 balloon, releasing one jet of the drug into the air. Carrying out inhalations

Step 1. Remove the protective cap from the inhaler mouthpiece, as shown in figure 1.

Step 2. Vigorously shake the inhaler.

Step 3. Make a slow, full exhalation. Do not exhale into the inhaler!

Step 4. Holding the balloon, as shown in Figure 2, tightly grasp the mouthpiece with your lips.

The balloon must be pointed upside down!

Step 5. Exercise as deep as possible, while simultaneously pushing the bottom of the balloon to release one inhalation dose.

Step 6. Hold the breath for a few seconds, then remove the mouthpiece from the mouth and slowly exhale through the nose.

Step 7. Put the protective cap on the mouthpiece of the inhaler.

Repeat steps 2-6 to obtain a second inhalation dose, if necessary. Cleaning the inhaler

Regularly (once a week), flush the mouthpiece of the inhaler, as shown in Figure 3.

Remove the metal can from the plastic case and

Rinse the case and cap with warm water. Do not use hot water. Thoroughly dry, but do not use for this heating devices. Place the can in the case and put on the cap. Do not immerse the metal can into the water.

The balloon is designed for 200 inhalations. After this, the cylinder should be replaced.

WARNING: a plastic mouthpiece designed specifically for the preparation Iperate aeronaut and serves for accurate dosing of the drug. The mouthpiece should not be used with other metered aerosols. Also you can not use Iperate aeronaut with any other adapters, except the mouthpiece supplied with the drug.

The contents of the cylinder are under pressure. The cylinder should not be opened and subjected to heating above 50 ° C!

Side effects:

Many of these unwanted effects may be due to anticholinergic and β-adrenergic properties of the drug Ipraterol aeronaut. Application of the drug Ipraterol aeronaut, Like any inhalation therapy, it can cause local irritation.

Determination of the frequency: very often (> 1/10), often (1/100 to 1/10) infrequently (from 1/1000 to 1/100), rare (from 1/1000 to 1/10000), very seldom (<1/10000).

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

Disorders from the metabolism and nutrition: rarely hypokalemia.

Disorders of the psyche: infrequently - nervousness; rarely - a sense of anxiety, mental disorders (mental disorders).

Disorders from the nervous system: infrequently - headache, dizziness, tremor.

Disorders from the side of the organ of vision: rarely - glaucoma, increased intraocular pressure, accommodation disorders, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, the appearance of an aura around objects and colored spots in front of the eyes.

Disorders from the heart: infrequently - tachycardia, palpitations; rarely - arrhythmia, atrial fibrillation, atrial fibrillation, supraventricular tachycardia, myocardial ischemia.

Disturbances from the respiratory system, chest and mediastinal organs: often - cough; infrequently - pharyngitis, dysphonia; rarely - bronchospasm, irritation of the pharynx, edema of the pharynx, laryngospasm, paradoxical bronchospasm, dryness of the pharynx.

Disorders from the gastrointestinal tract: infrequently - vomiting, dry mouth, nausea; rarely - stomatitis, glossitis, gastrointestinal motility disorders, diarrhea, constipation, edema of the oral cavity.

Disturbances from the skin and subcutaneous tissues: rarely - urticaria, skin rash, itching, sweating.

Disturbances from musculoskeletal and connective tissue: rarely - Muscle weakness, myalgia (muscle pains), muscle spasm.

Disorders from the kidneys and urinary tract: rarely - retention of urine.

Laboratory and instrumental data: infrequently - Increased systolic blood pressure; rarely - increase and decrease of diastolic blood pressure.

If any of the side effects listed in the manual are aggravated or you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms

Symptoms of overdose are mainly associated with the action of fenoterol. There may be symptoms caused by excessive stimulation of β-adrenergic receptors.The most likely occurrence of tachycardia, palpitation, tremor, hypertension or arterial hypotension, increasing the difference between systolic and diastolic blood pressure, angina pectoris, arrhythmias and feelings of "tides" of blood to the face, hyperglycemia, metabolic acidosis, hypokalemia. Possible symptoms of an overdose of ipratropium bromide (such as dry mouth, disruption of accommodation), given the great breadth of the therapeutic effect of the drug and the local mode of application, are usually of low birth and are of a transient nature.

Treatment

It is necessary to stop taking the drug.

It should take into account the monitoring of the acid-base balance of blood. Showing sedatives, tranquilizers, in severe cases - intensive therapy.

As a specific antidote, it is possible to use β-blockers, preferably β-selective blockers. However, one should remember about the possible strengthening of bronchial obstruction under the influence of β-blockers and carefully select the dose for patients suffering from bronchial asthma or chronic obstructive pulmonary disease, due to the danger of severe bronchospasm, which can lead to death.

Interaction:

Simultaneous use of other β-adrenomimetic drugs, anticholinergic drugs, incl. systemic action, and xanthine derivatives (eg, theophylline) may enhance the bronchodilator effect of the drug Iperate aeronaut and lead to aggravation of side effects.

Perhaps a significant weakening of the bronchodilator action of the drug with the simultaneous administration of β-blockers.

Hypokalemia associated with the use of β-adrenomimetics can be enhanced by the simultaneous administration of xanthine derivatives, glucocorticosteroids and diuretics. This fact should be given special attention in the treatment of patients with severe forms of obstructive airway disease. Hypokalemia can lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia can increase the negative effect of hypokalemia on the heart rhythm. In such cases, it is recommended to monitor the potassium level in the blood serum.

Caution should be used to assign β₂-adreneergic drugs for patients receiving monoamine oxidase inhibitors, tricyclic antidepressants, L-Dopa, L-teroxin, oxytocin, since these drugs are able to enhance the action of β-adrenergic agents.

Inhalation of agents for general anesthesia, such as halogenated hydrocarbon anesthetics (halothane, trichlorethylene, enflurane) may increase the adverse effect β -adrenergic agents for the cardiovascular system.

Special instructions:

In case of sudden rapid increase of dyspnea (difficulty breathing) should immediately consult a doctor.

In children, the drug should be used only as directed by a doctor and under the supervision of adults.

Use in children younger than 6 years is contraindicated, due to lack of experience.

Hypersensitivity:

After using the drug Ipraterol-aeroMr.active there may be reactions of immediate hypersensitivity, the signs of which in rare cases can be: urticaria, Quincke's edema, rash, bronchospasm, edema of the oropharynx, anaphylactic shock.

Paradoxical bronchospasm:

Ipraterol aeronaut, Like other inhaled drugs, it can cause paradoxical bronchospasm, which can threaten life.In the case of development of paradoxical bronchospasm, the use of the drug Ipraterol-aeroMr.active should immediately stop and go to alternative therapy.

Prolonged use:

- in patients suffering from bronchial asthma, Ipraterol-aeroMr.active should only be used as needed. In patients with mild forms of chronic obstructive pulmonary disease, symptomatic treatment may be preferable to regular use;

- in patients with bronchial asthma should be remembered the need to conduct or enhance anti-inflammatory therapy to control the inflammatory process of the airways and the course of the disease.

Regular use of increasing doses of drugs containing β₂-adrenomimetics, such as the drug Ipraterol aeronaut, for relief of bronchial obstruction can cause uncontrolled deterioration of the course of the disease. In the case of increased bronchial obstruction, an increase in the dose of β₂-adrenomimetics, including the drug Ipraterol aeronaut, more recommended for a long time is not only not justified, but also dangerous.To prevent a life-threatening deterioration in 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 the drug Iperate aeronaut only under medical supervision.

Disorders from the gastrointestinal tract:

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

Disorders from the side of the organ of vision:

Iperate aeronaut should be used with caution in patients predisposed to occlusive glaucoma. There are some reports of complications from the side of the eye (for example, increased intraocular pressure, mydriasis, occlusive glaucoma, eye pain) that developed when inhaled ipratropium bromide (or ipratropium bromide in combination with β₂-adrenomimetics) in the eyes. Symptoms of acute closed-angle glaucoma can be pain or discomfort in the eyes, blurred vision, the appearance of a halo around objects and color spots in front of the eyes in combination with corneal edema and red eyes due to conjunctival hyperemia.If any combination of these symptoms develops, the use of eye drops that reduce intraocular pressure and the immediate consultation of a specialist are indicated. Patients should be instructed about the proper use of the inhalation drug Ipraterol aeronaut. Especially careful to protect the eyes of patients who are predisposed to the development of glaucoma.

System Effects:

With such diseases as recent myocardial infarction (within the last 3 months), insufficiently controlled diabetes mellitus, severe organic diseases of the heart and blood vessels, hyperthyroidism, pheochromocytoma or obstruction of the urethra (for example, with prostatic hyperplasia or bladder neck obstruction) Iperate aeronaut should only be applied after a thorough risk / benefit assessment.

Effect on the cardiovascular system:

In postmarketing studies, rare cases of myocardial ischemia with β₂-adrenomimetics. Patients with concomitant serious heart disease (eg, coronary heart disease, arrhythmias or severe heart failure) receiving the drug Ipraterol aeronaut, should be warned about the need to consult a doctor in case of pain in the heart or other symptoms indicating a worsening of heart disease. It is necessary to pay attention to such symptoms as dyspnea and chest pain, since they can be both cardiac and pulmonary etiology.

Hypokalemia:

When applying β₂-adrenomimetics hypokalemia can occur (see section "Overdose").

Athletes use the drug Iperate aeronaut in connection with the presence in its composition of fenoterol can lead to positive results of doping tests.

Effect on the ability to drive transp. cf. and fur:Studies to study the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. In case of development of such adverse reactions as dizziness, tremor, disruption of accommodation, mydriasis and fogging of vision, one should refrain from driving vehicles and controlling mechanisms, as well as from engaging in other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

For 200 doses of the drug in a stainless steel balloon with a dosing valve and a spray nozzle. Each cylinder is accompanied with instructions for use in a cardboard bundle.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C, away from heating appliances. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003359

Date of registration:08.12.2015

Expiration Date:08.12.2020

The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia

Manufacturer: & nbsp

NATIVA, LLC Russia