Berotek N aerosol dosed for inhalation 100mcg/dose 10ml (200 doses) №1

Name:
Berotek N aer.dose.d/ing.100mcg/dose in vial. 10ml (200 doses) per pack. No. 1
Description:
10 ml in a metal can with a dosing valve. Spray with instructions for use in a cardboard box Main active ingredient Ipratropium bromide + fenoterol Release form Aerosol Dosage 20 mcg + 50 mcg / dose Pharmacological properties Pharmacodynamics Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. Preclinical studies have shown that it inhibits reflexes mediated by the vagus nerve by counteracting the effect of acetylcholine, a neurotransmitter released from this nerve. Anticholinergics prevent an increase in intracellular calcium concentration, which is caused by the interaction of acetylcholine with the muscarinic receptor of bronchial smooth muscle. Calcium release is mediated by a second messenger system consisting of IPG (inositol triphosphate) and DAG (diacylglycerol). Bronchodilation that occurs after inhalation of ipratropium bromide is a local and lung-specific effect that is not systemic. Fenoterol hydrobromide is a direct-acting sympathomimetic, a selective beta2-adrenergic receptor stimulant when taken in therapeutic doses. Stimulation of beta1-adrenergic receptors occurs when the drug is used in higher doses (for example, during tocolytic therapy). Binding of beta2-adrenergic receptors activates adenylate cyclase through the stimulatory Gs-protein with a subsequent increase in the formation of cAMP, which in turn activates protein kinase A. The latter phosphorylates target proteins in smooth muscle cells. This results in phosphorylation of myosin light chain kinase, inhibition of phosphoinosine hydrolysis, and opening of calcium-dependent fast potassium channels. Fenoterol hydrobromide relaxes the smooth muscles of the bronchi and blood vessels, and also prevents the development of bronchospasm caused by exposure to bronchoconstrictor factors such as histamine, methacholine, cold air and allergens (immediate type reaction). After taking the drug, the release of inflammatory mediators from mast cells is inhibited. In addition, after taking 0.6 mg of fenoterol, an increase in mucociliary transport is observed. Higher plasma concentrations of the drug, achieved after oral or, more often, after intravenous administration, inhibit uterine contractility. When taking high doses of the drug, effects are observed at the metabolic level: lipolysis, glycogenolysis, hyperglycemia and hypokalemia (the latter is due to increased absorption of K + by skeletal muscles). Beta-adrenergic effects of the drug at the level of the heart muscle, such as an increase in heart rate and increased myocardial contractility, are explained by the action of fenoterol on blood vessels, stimulation of beta2-adrenergic receptors of the heart, and when taking the drug in doses exceeding therapeutic, stimulation of beta1-adrenergic receptors. As with other beta-adrenergic agents, prolongation of the QTc interval has been reported. For fenoterol administered by metered dose inhaler, these phenomena were discrete and were observed at doses higher than recommended. However, systemic exposure after administration of the drug using nebulizers (solution for inhalation) was higher than with the introduction of the recommended doses using a metered dose inhaler. Clinical significance has not been established. The most commonly observed effect of beta-agonists is tremor. In contrast to the action on bronchial smooth muscle, the systemic effects of beta-adrenergic agonists are associated with the development of tolerance. With the combined use of these two active substances, the bronchodilator effect is achieved by acting on various pharmacological targets. These substances complement each other, as a result, the spasmolytic effect on the muscles of the bronchi is enhanced, and a wide range of therapeutic action is provided for bronchopulmonary diseases accompanied by narrowing of the airways. The complementary effect is such that a lower dose of beta-adrenergic agonist is required to achieve the desired effect, which allows you to individually select an effective dose with virtually no side effects. Pharmacokinetics The therapeutic effect of the combination of ipratropium bromide and fenoterol hydrobromide is created by local action on the respiratory tract. Therefore, the pharmacodynamics of bronchodilation is not related to the pharmacokinetics of active substances. After inhalation, 10-39% of the dose, depending on the dosage form, method of inhalation and the device used for inhalation, settles in the lungs. The rest of the dose remains in the mouthpiece, in the mouth and in the upper respiratory tract (oropharynx). The same amount of dose is deposited in the respiratory tract after inhalation of a metered-dose aerosol. After inhalation of an aqueous solution through the Respimat inhaler, the amount that entered the lungs was 2 times higher compared to inhalation with a metered-dose aerosol, while when inhaled through the Respimat inhaler, a much smaller amount of the active substance settles in the oropharynx. The proportion of the dose that reached the lungs quickly enters the circulatory system (within minutes). The active substance, which has settled in the oropharynx, is slowly swallowed and passes through the gastrointestinal tract. In this regard, systemic exposure is the result of bioavailability from the lungs and gastrointestinal tract. There are no data indicating that the pharmacokinetics of both ingredients in combination differ from the pharmacokinetics of the active substances separately. Fenoterol hydrobromide The ingested fraction is metabolized mainly to complex sulfate compounds. The absolute bioavailability of the drug when administered orally is low (about 1.5%). After intravenous administration of fenoterol in the urine for 24 hours, about 15% and 27% of the administered dose, respectively, are found in the free and conjugated state. After inhalation of BERODUAL N using a metered dose inhaler, about 1% of the dose is excreted as free fenoterol in the urine within 24 hours. Based on this information, the calculated total systemic bioavailability of fenoterol hydrobromide after inhalation administration is about 7%. The distribution of fenoterol in blood plasma after intravenous administration occurs according to a three-phase pharmacokinetic model, the final elimination half-life is about 3 hours. In this three-phase pharmacokinetic model, the apparent volume of distribution at equilibrium (Vdss) is approximately 189 L (? 2.7 L/kg). About 40% of the substance binds to plasma proteins. Fenoterol and its metabolites do not cross the blood-brain barrier. The total clearance of fenoterol is 1.8 l / min, renal clearance is 0.27 l / min. Ipratropium bromide The cumulative renal excretion (0-24 hours) of ipratropium (parent compound) approaches 46% of the intravenous dose, is less than 1% of the oral dose, and approximately 3-13% of the dose of BERODUAL N administered using a metered dose inhaler. Based on these data, the overall systemic bioavailability of ipratropium bromide for oral and inhaled use is 2% and 7 to 28%, respectively. The swallowed portion of a dose of ipratropium bromide does not have a significant systemic effect. The kinetic parameters characterizing the distribution of ipratropium are calculated based on the plasma concentrations of the drug after intravenous administration. There is a rapid two-phase decrease in plasma concentrations. The apparent volume of distribution at equilibrium (Vdss) is about 176 l (“2.4 l/kg). The drug is minimally (less than 20%) bound to plasma proteins. Preclinical studies conducted on mice and dogs showed that ipratropium, being a Quaternary amine; does not penetrate the blood-brain barrier. The half-life in the last phase of elimination is about 1.6 hours. The total clearance of ipratropium is 2.3 l/min and the renal clearance is 0.9 l/min. After intravenous administration, about 60% of the dose is metabolized in the liver by oxidation. Indications for use Prevention and treatment of shortness of breath in chronic obstructive airway disorders: allergic and non-allergic (endogenous) bronchial asthma, exercise-induced asthma, chronic obstructive bronchitis, complicated or uncomplicated by emphysema. To prepare (“open the lungs”) and maintain aerosol therapy with corticosteroids, mucolytics, saline solutions, cromoglycic acid and antibiotics. Long-term treatment should be accompanied by appropriate anti-inflammatory therapy. Dosage and administration Dosage depends on the nature and severity of the disease. For adults and children over 6 years of age, the following doses are recommended: For the relief of a sudden spasm of the smooth muscles of the bronchi with an attack of shortness of breath, inhalation of one therapeutic dose (100 μg of fenoterol hydrobromide and 40 μg of ipratropium bromide) is recommended, which corresponds to 2 inhalation doses. As a rule, one inhalation dose is sufficient to provide a significant improvement in bronchial patency. If there is no noticeable improvement within 5 minutes after the first 1-2 inhalation doses, an additional 1-2 inhalation doses may be used. Severe dyspnoea and failure of the second therapeutic dose may indicate the need for additional doses. In these cases, patients should immediately seek medical attention. If long-term treatment with BERODUAL N metered dose inhaler is required, the recommended dose is 1-2 inhalation doses 3-4 times a day. For the treatment of bronchial asthma, the BERODUAL H metered dose inhaler should be used only as needed. In general, the timing and dose of each administration should be adjusted according to the symptoms. It is necessary to provide at least a 3-hour interval between the administration of the drug. The daily dose should not exceed 12 inhalation doses, since higher doses usually do not have an additional therapeutic effect, but can lead to the development of potentially serious side effects. For targeted prevention of asthma attacks of physical effort or expected contact with an allergen, it is recommended to take 2 inhalation doses of the drug 10-15 minutes before the expected physical activity / contact with the allergen. To achieve successful therapy, patients should be instructed on how to use the MDI correctly. However, the usual precautions should be observed when using drugs during pregnancy. It is necessary to take into account the ability of fenoterol to have an inhibitory effect on uterine contractility. The use of beta-agonists at the end of pregnancy or in high doses can cause negative consequences in newborns (tremor, tachycardia, fluctuations in blood glucose levels, hypokalemia). Breastfeeding period Preclinical studies have shown the ability of fenoterol to be excreted in breast milk. Data confirming the excretion of ipratropium bromide with breast milk have not been received. The appearance of ipratropium after inhalation in breast milk at a concentration that can affect the infant is unlikely. Caution should be exercised when using BERODUAL N in a woman during breastfeeding. Fertility There are no clinical data on the effect of the combination of ipratropium bromide and fenoterol hydrobromide on fertility. Preclinical studies conducted with ipratropium bromide and fenoterol hydrobromide alone have not demonstrated a negative effect on fertility. Precautions In case of unexpected rapid increase in shortness of breath (difficulty breathing), you should immediately consult a doctor. BERODUAL N, like other inhaled drugs, can cause paradoxical bronchospasm, which can be life threatening. In the event of the development of paradoxical bronchospasm, the use of BERODUAL N should be immediately discontinued and switched to alternative therapy. BERODUAL N should only be used after a careful assessment of the risk/benefit ratio, especially when using doses higher than recommended, in the following diseases: diabetes mellitus with inadequate glycemic control, recent myocardial infarction, myocarditis, severe organic diseases of the heart or blood vessels (in particular, in the presence of tachycardia), hyperthyroidism, pheochromocytoma. When using sympathomimetic agents, including BERODUAL N, effects from the cardiovascular system may occur. Rare cases of myocardial ischemia have been reported in post-marketing studies and published literature with beta-agonists. Patients with concomitant serious heart disease (for example, coronary heart disease, arrhythmias, or severe heart failure) receiving BERODUAL N should be warned about the need to consult a doctor in case of pain in the heart or other symptoms indicating worsening heart disease. It is necessary to pay attention to symptoms such as shortness of breath and chest pain, as they can be of both pulmonary and cardiac etiology. There are isolated reports of complications from the organ of vision (for example, mydriasis, increased intraocular pressure, angle-closure glaucoma and pain in the eyes) that developed when inhaled ipratropium bromide or ipratropium bromide in combination with beta-adrenergic agonists got into the eyes. Attention! Patients should be instructed on the correct use of BERODUAL N metered-dose aerosol. Care must be taken to prevent the drug from getting into the eyes. Symptoms of acute angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo, colored spots before the eyes, redness of the eyes due to injection of conjunctival vessels, and corneal edema. If any of these symptoms appear, immediate consultation with a specialist is necessary and the use of miotic agents is indicated. In patients with a history of cystic fibrosis, gastrointestinal motility disorders may occur during therapy with inhaled anticholinergics. This effect is reversible and disappears after treatment is stopped. Long-term use of the drug In patients with bronchial asthma, BERODUAL N should be used only as needed. In patients with mild chronic obstructive pulmonary disease, on-demand symptomatic treatment may be preferable to regular use of the drug. In patients with asthma or chronic obstructive pulmonary disease responding to steroid therapy, one should be aware of the need to conduct or increase anti-inflammatory therapy to control the inflammatory process of the airways and the course of the disease. In patients with bronchial asthma, the regular use of increasing doses of drugs containing beta-adrenergic agonists, such as BERODUAL N, to relieve bronchial obstruction, can cause an uncontrolled worsening of the course of the disease. In the case of increased bronchial obstruction, an increase in the dose of beta-adrenergic agonists, including BERODUAL N, 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 corticosteroids, or adjusting the dose of anti-inflammatory therapy. An increased risk of serious complications of bronchial asthma, including fatal ones, has been registered with the use of high and very high doses of inhaled beta2-agonists for a long period of time without adequate anti-inflammatory therapy. A causal relationship has not been definitely established. Perhaps the inadequacy of anti-inflammatory therapy is of vital importance. Other sympathomimetic bronchodilators should be administered simultaneously with BERODUAL H only under medical supervision. Potentially severe hypokalemia may occur with high doses of beta2-agonists. It is recommended to monitor the concentration of potassium in the blood at its initially low level. An increase in blood glucose levels is possible. In this regard, it is recommended to control blood glucose levels in patients with diabetes mellitus. After the use of BERODUAL N, in rare cases, immediate hypersensitivity reactions may occur: urticaria, angioedema, rash, bronchospasm; swelling of the oropharynx and allergic reactions. This medicine contains 99% ethanol (alcohol; less than 100 mg/dose). The use of BERODUAL N can lead to positive results in doping tests. Interaction with other drugs Long-term co-administration of BERODUAL N with other anticholinergic drugs has not been studied and is therefore not recommended. The simultaneous use of the following drugs / groups of drugs may affect the action of BERODUAL N. Enhance the effect and / or increase the risk of adverse reactions: other beta-adrenergic agents (any route of administration); other anticholinergic drugs (any route of administration); xanthine derivatives (eg theophylline); anti-inflammatory drugs (corticosteroids); monoamine oxidase inhibitors; tricyclic antidepressants; halogenated hydrocarbon anesthetics (for example, halothane, trichlorethylene or enflurane), since they can increase the effect on the cardiovascular system. Reduces the effectiveness of BERODUAL N: the simultaneous use of beta-blockers. Other possible reactions: Hypokalemia caused by the use of a beta2-agonist may be exacerbated by the simultaneous use of xanthine derivatives, glucocorticosteroids and diuretics. This should be taken into account in particular when treating patients with severe forms of obstructive airway disease. Hypokalemia may lead to an increased risk of arrhythmias in patients taking digoxin. In addition, the negative effect of hypokalemia on heart rate can be exacerbated by hypoxia. In such cases, it is recommended to monitor the level of potassium in the blood serum. The risk of developing an acute attack of glaucoma increases if nebulized ipratropium bromide alone or in combination with a beta-agonist gets into the eyes. Contraindications BERODUAL N is contraindicated in patients with known hypersensitivity to fenoterol hydrobromide and/or ipratropium bromide, atropine-like substances, or any of the excipients. BERODUAL N is also contraindicated in patients with hypertrophic obstructive cardiomyopathy and tachyarrhythmia. Overdose Symptoms Depending on the degree of overdose, the following side effects, typical of beta-adrenomimetics, may occur: flushing sensation, delirium, headache, tachycardia, palpitations, arrhythmia, arterial hypotension up to shock, increased blood pressure, anxiety, pain in the chest, agitation, extrasystoles may occur and cases of metabolic acidosis, as well as hypokalemia, have been reported with the use of fenoterol at doses higher than those recommended, approved for indications for BERODUAL N. Symptoms of an overdose of ipratropium bromide (such as dry mouth, disturbance of accommodation) are usually weakly expressed due to the low systemic bioavailability of inhaled ipratropium. Therapy Treatment with BERODUAL H should be discontinued. It is necessary to monitor the indicators of acid-base balance and blood electrolytes. The introduction of sedatives, tranquilizers is shown; in severe cases, intensive supportive care, including hospitalization, may be required. As an antidote for fenoterol, it is possible to use beta-blockers (preferably beta-blockers); however, it is necessary to take into account the possibility of worsening bronchial patency, which requires careful selection of the dose of the drug in patients with bronchial asthma or COPD, due to the risk of provoking severe bronchospasm, which can be fatal. Composition One inhalation dose contains active ingredients: ipratropium bromide monohydrate 21 mcg (0.021 mg), which corresponds to 20 mcg (0.020 mg) of ipratropium bromide, and fenoterol hydrobromide 50 mcg (0.050 mg); excipients: anhydrous citric acid, purified water, absolute ethanol, tetrafluoroethane (HFA 134a). OverdoseSymptoms Depending on the degree of overdose, the following side effects, typical of beta-adrenomimetics, may appear: flushing sensation, delirium, headache, tachycardia, palpitations, arrhythmia, arterial hypotension up to shock, increased blood pressure, anxiety, pain in chest, agitation, possible extrasystoles and cases of metabolic acidosis, as well as hypokalemia, have been reported with the use of fenoterol at doses higher than those recommended, approved for indications for BERODUAL N. Symptoms of an overdose of ipratropium bromide (such as dry mouth, disturbance of accommodation) are usually mild due to the low systemic bioavailability of inhaled ipratropium. Therapy Treatment with BERODUAL H should be discontinued. It is necessary to monitor the indicators of acid-base balance and blood electrolytes. The introduction of sedatives, tranquilizers is shown; in severe cases, intensive supportive care, including hospitalization, may be required. As an antidote for fenoterol, it is possible to use beta-blockers (preferably beta-blockers); however, it is necessary to take into account the possibility of worsening bronchial patency, which requires careful selection of the dose of the drug in patients with bronchial asthma or COPD, due to the risk of provoking severe bronchospasm, which can be fatal. Side effects Many of the side effects listed below can be attributed to the anticholinergic and beta-adrenergic properties of BERODUAL N. Like other drugs used by inhalation, BERODUAL N can cause symptoms of local irritation. The most commonly reported side effects include: cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, increased systolic blood pressure and nervousness. The frequency of occurrence of side effects is indicated as: very often (? 1/10); often (from? 1/100 to <1/10); infrequently (from? 1/1000 to <1/100); rarely (from? 1/10000 to <1/1000); very rarely (<1/10000); unknown (cannot be established based on the available data). From the immune system: rarely - anaphylactic reaction, hypersensitivity. Mental disorders: infrequently - nervousness; rarely - anxiety, mental disorder. From the nervous system: infrequently - headache, tremor, dizziness; unknown - hyperactivity. On the part of the organ of vision: rarely - glaucoma, increased intraocular pressure, disturbance of accommodation, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, visual halos. From the side of the cardiovascular system: infrequently - tachycardia, palpitations; rarely - arrhythmia, atrial fibrillation, supraventricular tachycardia, myocardial ischemia. From the respiratory system: often - cough; infrequently - pharyngitis, dysphonia; rarely - bronchospasm, throat irritation, laryngeal edema, laryngospasm, paradoxical bronchospasm, dry throat. From the gastrointestinal tract: infrequently - vomiting, nausea, dry mouth; rarely - stomatitis, glossitis, dysmotility of the gastrointestinal tract, diarrhea, constipation, swelling of the oral mucosa, heartburn. From the skin and subcutaneous tissues: rarely - urticaria, rash, itching, angioedema, petechiae, hyperhidrosis. On the part of the musculoskeletal and connective tissue: rarely - muscle weakness, muscle spasms, myalgia. From the side of the kidneys and urinary tract: rarely - urinary retention. From the side of laboratory and instrumental data: infrequently - an increase in systolic blood pressure; rarely - a decrease in diastolic blood pressure, thrombocytopenia. Storage conditionsStore in a place protected from direct sunlight at a temperature below 25°C. Do not expose to high temperatures or freeze. Keep out of the reach of children. inhalations 100mcg/dose 10ml (200 doses) #1