Berodual solution 500 + 250mkg, 20 ml

Prevention and symptomatic treatment of chronic obstructive airway diseases with reversible bronchospasm: bronchial asthma, chronic obstructive bronchitis, complicated or uncomplicated by emphysema.

Inhalation

Solution for inhalation. Adults and children over 12 years of age for relief of seizures - 20Ц80 drops (1Ц4 ml). With long-term therapy - 1-2 ml (20-40 drops) up to 4 times a day. In cases of moderately pronounced bronchospasm or the need for assisted ventilation of the lungs - 0.5 ml (10 drops). Children 6-12 years old for relief of seizures - 0.5-1 ml (10-20 drops) once, for severe attacks - 2-3 ml (40-60 drops), with prolonged therapy - 0.5-1 ml ( 10-20 drops) 4 times a day, with moderate bronchospasm - 0.5 ml (10 drops). Children under 6 years of age (body weight less than 22 kg) (only under medical supervision) at the rate of 25 ?g of ipratropium bromide and 50 ?g of fenoterol hydrobromide per 1 kg of body weight, up to 0.5 ml (10 drops) up to 3 times a day.

The recommended dose immediately before use is diluted with physiological solution to a volume of 3-4 ml and inhaled through a nebulizer for 6-7 minutes until the solution is completely consumed. Berodual solution for inhalation should not be diluted with distilled water. The solution should be diluted immediately before use, the diluted solution remaining after inhalation should be destroyed.

The dose depends on the mode of inhalation and the technical characteristics of the nebulizer. The duration of inhalation can be controlled through the volume of the diluted solution.

Berodual inhalation solution can be applied using various commercially available inhalation devices. In the presence of a centralized stationary oxygen supply, the solution is best administered at a rate of 6Ц8 l / min. If necessary, repeated inhalations are carried out at intervals of at least 4 hours.

Spray can. Adults and children over 6 years old are prescribed 2 inhalation doses. If relief of breathing does not occur within 5 minutes, 2 more inhalation doses can be prescribed. If 4 inhalations are ineffective, you should immediately seek medical help.

With long-term and intermittent therapy - 1-2 doses 3 times a day (up to 8 inhalations a day).

To obtain the maximum effect, it is necessary to use the metered aerosol correctly.

Before using the metered aerosol for the first time, shake the can and press the bottom of the can twice.

Each time you use a metered aerosol, the following rules must be observed:

1. Remove the protective cap.

2. Take a slow, deep breath.

3. While holding the balloon, clasp the tip with your lips. The cylinder must be upside down.

4. Making the deepest possible inhalation, simultaneously quickly press the bottom of the balloon until one inhalation dose is released. Hold your breath for a few seconds, then remove the tip from your mouth and exhale slowly. Repeat steps to obtain the second inhalation dose.

5. Put on the protective cap.

6. If the aerosol can has not been used for more than 3 days, before use, press the bottom of the can once until a cloud of aerosol appears.

The balloon is designed for 200 inhalations. After that, the cylinder should be replaced. Although some content may remain in the balloon, the amount of drug released by inhalation may be reduced.

The balloon is opaque, so the amount of the drug in the balloon can be determined only in the following way: after removing the protective cap, the balloon is immersed in a container filled with water. The amount of the drug is determined depending on the position of the balloon in the water.

The handpiece should be kept clean and, if necessary, can be rinsed in warm water. After using soap or detergent, rinse the handpiece thoroughly with clean water.

Warning: the plastic adapter for the mouth is specially designed for the metered aerosol Berodual N and serves for accurate dosing of the drug. The adapter must not be used with other metered aerosols. Do not use metered-dose tetrafluoroethane-containing aerosol Berodual N with any other adapters, except for the adapter supplied with the cylinder.

The contents of the cylinder are under pressure. The cylinder must not be opened and heated above 50 ? C.

Solution for inhalation

1 ml

ipratropium bromide 0.261 mg (which corresponds to 0.25 mg ipratropium bromide anhydrous)

fenoterol hydrobromide 0.5 mg

in dropper bottles of 20 ml (1 ml = 20 drops); in the box 1 bottle.

Hypersensitivity, hypertrophic obstructive cardiomyopathy, tachyarrhythmia, pregnancy (I trimester).

pharmachologic effect

Combined bronchodilator drug. Contains two components with bronchodilator activity: ipratropium bromide - an m-anticholinergic antagonist, and fenoterol hydrobromide - a beta2-adrenergic agonist.

Bronchodilation with inhalation of ipratropium bromide is mainly due to local rather than systemic anticholinergic action.

Ipratropium bromide is a quaternary ammonium derivative with anticholinergic (parasympatholytic) properties. The drug inhibits reflexes caused by the vagus nerve, counteracting the effects of acetylcholine, a mediator released from the endings of the vagus nerve. Anticholinergics prevent an increase in intracellular calcium concentration, which occurs due to the interaction of acetylcholine with the muscarinic receptor located on the smooth muscles of the bronchi. The release of calcium is mediated by a system of secondary mediators, which include ITP (inositol triphosphate) and DAG (diacylglycerol).

In patients with bronchospasm associated with COPD (chronic bronchitis and pulmonary emphysema), a significant improvement in lung function (an increase in forced expiratory volume in 1 sec (FEV1) and peak expiratory flow rate by 15% or more) was noted within 15 minutes, the maximum effect was achieved after 1-2 hours and continued in most patients up to 6 hours after administration.

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

Fenoterol hydrobromide selectively stimulates ?2-adrenergic receptors at a therapeutic dose. Stimulation of? 1-adrenergic receptors occurs when using 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 administration, fenoterol blocks the release of inflammatory mediators and bronchial obstruction from mast cells. In addition, with the use of fenoterol at a dose of 600 ?g, an increase in mucociliary clearance was noted.

The beta-adrenergic effect of the drug on cardiac activity, such as an increase in the frequency and strength of heart contractions, is due to the vascular action of fenoterol, stimulation of the ?2-adrenergic receptors of the heart, and when used in doses exceeding therapeutic ones, stimulation of the ?1-adrenergic receptors.

As with the use of other beta-adrenergic drugs, an increase in the QTc interval has been observed when used in high doses. When using fenoterol with metered-dose aerosol inhalers (MDIs), this effect was inconsistent and was noted when used in doses higher than recommended. However, after using fenoterol with nebulizers (solution for inhalation in vials with a standard dose), the systemic exposure may be higher than when using the drug with the help of MDI in recommended doses. The clinical significance of these observations has not been established.

The most commonly observed effect of ?-adrenergic receptor agonists is tremor. In contrast to the effects on the smooth muscles of the bronchi, tolerance can develop to the systemic effects of ?-adrenergic receptor agonists. The clinical significance of this manifestation has not been clarified. Tremor is the most frequent undesirable effect with the use of ?-adrenergic receptor agonists.

With the combined use of ipratropium bromide and fenoterol, the bronchodilatory effect is achieved by acting on various pharmacological targets. These substances complement each other, as a result, the antispasmodic effect on the muscles of the bronchi is enhanced and a wide range of therapeutic action is provided for bronchopulmonary diseases, accompanied by constriction of the airways. The complementary action is such that to achieve the desired effect, a lower dose of the beta-adrenergic component is required, which allows you to individually select an effective dose with virtually no side effects of BerodualЃ.

In acute bronchoconstriction, the effect of the drug develops quickly, which makes it possible to use it in acute attacks of bronchospasm.

Indications of the drug

prevention and symptomatic treatment of chronic obstructive airway diseases with reversible airway obstruction, such as bronchial asthma and especially COPD, chronic obstructive bronchitis with or without emphysema.

Dosage regimen

Treatment should be carried out under medical supervision (for example, in a hospital setting). Home treatment is possible only after consulting a doctor in cases where a fast-acting ?-adrenergic receptor agonist in a low dose is not effective enough. Also, the solution for inhalation can be recommended to patients in the case when the inhalation aerosol cannot be used or if it is necessary to use higher doses.

The dose should be selected individually, depending on the severity of the attack. Treatment is usually started at the lowest recommended dose and stopped after sufficient symptom relief has been achieved.

The following doses are recommended:

In adults (including the elderly) and adolescents over 12 years of age with acute attacks of bronchospasm, depending on the severity of the attack, doses can vary from 1 ml (1 ml = 20 drops) to 2.5 ml (2.5 ml = 50 drops). In especially severe cases, it is possible to use the drug in doses up to 4 ml (4 ml = 80 drops).

In children aged 6-12 years with acute attacks of bronchial asthma, depending on the severity of the attack, doses can vary from 0.5 ml (0.5 ml = 10 drops) to 2 ml (2 ml = 40 drops).

In children under 6 years of age (body weight less than 22 kg), due to the fact that information on the use of the drug in this age group is limited, it is recommended to use the following dose (only subject to medical supervision): 0.1 ml (2 drops) per kg body weight, but not more than 0.5 ml (10 drops).

Terms of use of the drug

The solution for inhalation should only be used for inhalation (with a suitable nebulizer) and should not be used orally.

Treatment should usually begin at the lowest recommended dose.

The recommended dose should be diluted with 0.9% sodium chloride solution to a final volume of 3-4 ml and applied (completely) using a nebulizer.

The solution for inhalation should not be diluted with distilled water.

Dilution of the solution should be carried out each time before use; the remains of the diluted solution should be destroyed.

The diluted solution should be used immediately after preparation.

The duration of inhalation can be controlled by the consumption of the diluted solution.

The inhalation solution can be applied using a variety of commercial nebulizer models. The dose to the lungs and the systemic dose depend on the type of nebulizer used and may be higher than the corresponding doses when using a metered aerosol (depending on the type of inhaler). When using a centralized oxygen system, the solution is best used at a flow rate of 6-8 l / min.

The instructions for use, maintenance and cleaning of the nebulizer must be followed.

Side effect

Many of the listed undesirable effects may be due to the anticholinergic and beta-adrenergic properties of the drug. BerodualЃ, like any inhalation therapy, can cause local irritation. Adverse drug reactions were determined on the basis of data obtained in clinical trials and in the course of pharmacological surveillance of the drug after its registration.

The most common side effects reported in clinical trials were cough, dry mouth, headache, tremors, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, increased systolic blood pressure, and nervousness.

Determination of the categories of the frequency of adverse reactions that may occur during treatment: very often (? 1/10), often (from? 1/100 to <1/10), infrequently (from? 1/1000 to <1/100), rarely (from? 1/10 000 to <1/1000), very rarely (<1/10 000); the frequency is unknown (the frequency cannot be estimated from the available data).

From the immune system: rarely * - anaphylactic reaction, hypersensitivity, angioedema; rarely - urticaria.

From the side of metabolism: rarely * - hypokalemia.

From the nervous system and psyche: infrequently - nervousness, headache, tremors, dizziness; rarely - excitement, mental disturbances.

From the side of the organ of vision: rarely * - glaucoma, increased intraocular pressure, accommodation disturbances, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, the appearance of a halo around objects.

From the side of the cardiovascular system: infrequently - tachycardia, palpitations, increased systolic blood pressure; rarely - arrhythmia, atrial fibrillation, supraventricular tachycardia , myocardial ischemia , increased diastolic blood pressure.

From the respiratory system: often - cough; infrequently - pharyngitis, dysphonia; rarely - bronchospasm, pharyngeal irritation, pharyngeal edema, laryngospasm , paradoxical bronchospasm , dryness of the pharynx *.

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

Skin and subcutaneous tissue disorders: itching, hyperhidrosis *.

From the musculoskeletal system: rarely - muscle weakness, muscle spasm, myalgia.

From the urinary system: rarely - urinary retention.

Contraindications for use

• hypertrophic obstructive cardiomyopathy;

• tachyarrhythmia;

• hypersensitivity to fenoterol hydrobromide and other components of the drug;

• hypersensitivity to atropine-like drugs.

The drug should be prescribed with caution for angle-closure glaucoma, arterial hypertension, insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic diseases of the heart and blood vessels, coronary artery disease, hyperthyroidism, pheochromocytoma, urinary tract obstruction, cystic fibrosis, during pregnancy, during breastfeeding.

Application during pregnancy and lactation

Existing clinical experience has shown that fenoterol and ipratropium do not adversely affect pregnancy. However, when using these drugs 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.

Application for impaired renal function

The drug should be prescribed with caution in case of bladder neck obstruction.

Use in elderly patients

Application is possible according to the dosage regimen.

Overdose

Symptoms: symptoms of overdose are usually associated mainly with the action of fenoterol (the appearance of symptoms associated with excessive stimulation of ?-adrenergic receptors). The most likely appearance is tachycardia, palpitations, tremors, an increase or decrease in blood pressure, an increase in the difference between systolic and diastolic blood pressure, angina pectoris, arrhythmias and hot flashes. Metabolic acidosis and hypokalemia have also been observed.

Overdose symptoms due to the action of ipratropium bromide (such as dry mouth, impaired accommodation of the eyes) are mild and transient in nature, which is explained by the wide breadth of the therapeutic effect of the drug and its local use.

Treatment: it is necessary to stop using the drug. It is necessary to take into account the data of monitoring the acid-base balance of the blood. Shown are sedatives, tranquilizers, in severe cases - intensive therapy.

As a specific antidote, it is possible to use beta-blockers, preferably selective beta1-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 suffering from bronchial asthma or COPD, due to the danger of severe bronchospasm, which can be fatal.

Drug interactions

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

With the simultaneous use of other beta-adrenergic agonists, anticholinergics of systemic action, xanthine derivatives (for example, theophylline), the bronchodilatory effect of BerodualЃ may be enhanced. The simultaneous appointment of other beta-adrenergic agonists that enter the systemic circulation of anticholinergics or xanthine derivatives (for example, theophylline) may lead to increased side effects.

Hypokalemia associated with the use of beta-adrenergic agonists can be enhanced by the simultaneous use of xanthine derivatives, corticosteroids and diuretics. This fact should be given special attention in the treatment of patients with severe obstructive airways disease.

Hypokalemia may increase the risk of arrhythmias in patients receiving digoxin. In addition, hypoxia can exacerbate the negative effects of hypokalemia on heart rate. In such cases, it is recommended to monitor the concentration of potassium in the blood serum.

Beta2-adrenomimetics should be used with caution in patients receiving MAO inhibitors and tricyclic antidepressants, because these drugs are able to enhance the action of beta-adrenergic drugs.

The use of inhaled halogenated anesthetics, such as halothane, trichlorethylene or enflurane, can increase the effects of beta-adrenergic drugs on the cardiovascular system.

The combined use of the drug with cromoglycic acid and / or corticosteroids increases the effectiveness of therapy.