pharmachologic effect
Ipraterol-aeronative contains two components with bronchodilator activity: ipratropium bromide - an m-anticholinergic blocker and fenoterol - a β2-adrenergic agonist. Bronchodilation with inhaled ipratropium bromide is due primarily to local rather than systemic anticholinergic effects.
When ipratropium bromide and fenoterol are used together, the bronchodilator (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 is enhanced and a greater breadth of therapeutic action is provided for bronchopulmonary diseases accompanied by airway obstruction. The complementary effect is such that to achieve the desired effect, a lower dose of the β-adrenergic component is required, which allows you to individually select an effective dose with virtually no side effects.
Directions for use and doses
The dose should be selected individually. Medical supervision is required during therapy. The following doses are recommended:
In adults (including older adults) and adolescents over 12 years of age:
- Acute attacks of bronchial asthma
For mild to moderate attacks, 1 ml (20 drops) is recommended in many cases. In particularly severe cases, for example in patients in intensive care units, if the doses indicated above are ineffective, higher doses, up to 2.5 ml (50 drops), may be required. The maximum dose can reach 4.0 ml (80 drops). The maximum daily dose is 8.0 ml (160 drops).
- Course and long-term treatment
If repeated use is necessary, for each administration, use 1-2 ml (20-40 drops) up to 4 times a day.
In case of moderate bronchospasm or as an adjuvant during ventilation, a dose whose lower level is 0.5 ml (10 drops) is recommended.
In children aged 6-12 years:
- Acute attacks of bronchial asthma
In many cases, 0.5 - 1 ml (10 -20 drops) is recommended for quick relief of symptoms.
In severe cases, if a dose of 1 ml (20 drops) is ineffective, higher doses, up to 2 ml (40 drops), may be required.
In particularly severe cases, if a dose of up to 2.0 ml (40 drops) is ineffective, it is possible to use (subject to medical supervision) a maximum dose of 3.0 ml (60 drops).
The maximum daily dose can reach 4.0 ml (80 drops).
- Course and long-term treatment
If repeated use is necessary, use 0.5 - 1 ml (10-20 drops) for each administration up to 4 times a day.
In cases of moderate bronchospasm or as an aid during ventilation, the recommended dose is 0.5 ml (10 drops).
In children under 6 years of age (who weigh less than 22 kg):
Due to the fact that information on the use of the drug in this age group is limited, the following dose is recommended (only under medical supervision): about 25 mcg ipratropium bromide and 50 mcg fenoterol hydrobromide = 0.1 ml (2 drops) per kg body weight body (per dose), but not more than 0.5 ml (10 drops) (per dose). The maximum daily dose is 1.5 ml.
The inhalation solution should only be used for inhalation (with a suitable nebulizer) and should not be administered orally.
Treatment should usually begin with the lowest recommended dose. The recommended dose is to be diluted with 0.9% sodium chloride solution to a final volume of 3-4 ml and administered (entirely) using a nebulizer. Ipraterol-native solution for inhalation should not be diluted with distilled water.
The solution must be diluted each time before use, and the remaining diluted solution must be destroyed.
The diluted solution should be used immediately after preparation.
Dosage may depend on the method of inhalation and the type of nebulizer.
The duration of inhalation can be controlled by the consumption of the diluted volume.
Ipraterol-native solution for inhalation can be used using various commercial models of nebulizers. In cases where wall oxygen is available, the solution is best used at a flow rate of 6-8 liters per minute. It is necessary to follow the instructions for use, maintenance and cleaning of the device supplied with the nebulizer.
Ipraterol-Aeronativ solution for inhalation 0.25 mg/ml + 0.5 mg/ml bottle 20 ml
A country
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Ipratropium bromide + Fenoterol
Compound
Bottle 20 ml
Ipratropium bromide monohydrate 0.261 mg, fenoterol hydrobromide 0.5 mg per 1 ml. Excipients: sodium benzoate 0.5 mg, disodium edetate 0.5 mg, citric acid monohydrate 1.5 mg, sodium hydroxide to pH 3.2, water for up to 1 ml.
pharmachologic effect
Combined bronchodilator drug. Contains two components with bronchodilator activity: ipratropium bromide - an m-anticholinergic blocker, and fenoterol hydrobromide - a beta2-adrenergic agonist. Ipratropium bromide is a quaternary ammonium derivative with anticholinergic (parasympatholytic) properties. Bronchodilation with inhaled ipratropium bromide is due primarily to local rather than systemic anticholinergic effects. Ipratropium bromide inhibits reflexes caused by the vagus nerve by counteracting the effects of acetylcholine, a neurotransmitter released from the endings of the vagus nerve. Anticholinergics prevent an increase in the intracellular concentration of calcium ions, which occurs due to the interaction of acetylcholine with muscarinic receptors located on the smooth muscles of the bronchi. The release of calcium ions is mediated by a system of secondary mediators, which include inositol triphosphate and diacylglycerol. Ipratropium bromide does not have a negative effect on mucus secretion in the respiratory tract, mucociliary clearance and gas exchange. Fenoterol selectively stimulates β2-adrenergic receptors in a therapeutic dose. Stimulation of β1-adrenergic receptors occurs when fenoterol is used in 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 mediators of inflammation and bronchial obstruction from mast cells. In addition, when using fenoterol in higher doses, an increase in mucociliary clearance was observed. The 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 β2-adrenergic receptors of the heart, and when used in doses exceeding therapeutic doses, stimulation of β1-adrenergic receptors. As with other beta-adrenergic drugs, prolongation of the QTc interval has been observed when used in high doses. The most common adverse effect with β-adrenergic agonists is tremor. In contrast to the effect on bronchial smooth muscle, tolerance to the systemic effect of β-adrenergic receptor agonists may develop, but the clinical significance of this manifestation is not clear. When ipratropium bromide and fenoterol 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 is enhanced and a greater breadth of therapeutic action is provided for bronchopulmonary diseases accompanied by airway obstruction. 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 an effective dose with virtually no side effects. In patients with bronchospasm associated with COPD (chronic bronchitis and emphysema), a significant improvement in lung function (increase in FEV1 and peak expiratory flow by 15% or more) was noted within 15 minutes, the maximum effect was achieved after 1-2 hours and lasted for most patients within 6 hours after administration.
Indications for use
Prevention and symptomatic treatment of obstructive airway diseases with reversible airway obstruction, such as bronchial asthma and, especially, COPD, chronic bronchitis with or without emphysema.
Mode of application
Solution for inhalation The dose should be selected individually, depending on the severity of the attack. Treatment is usually started at the lowest recommended dose and stopped once sufficient relief of symptoms has been achieved. Treatment should be carried out under medical supervision (for example, in a hospital setting). Treatment at home is possible only after consultation with a doctor in cases where a fast-acting β-adrenergic receptor agonist in a low dose is not effective enough. An inhalation solution may be recommended to patients when an inhalation aerosol cannot be used or when higher doses are required. In adults (including the elderly) and adolescents over 12 years of age during 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 reaching 4 ml (4 ml = 80 drops). In children aged 6-12 years during 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) Rules for use of the drug The solution for inhalation should be used only for inhalation (with a suitable nebulizer) and not administered orally. The recommended dose should be diluted with 0.9% sodium chloride solution to a final volume of 3-4 ml, and apply (entirely) using a nebulizer. The solution for inhalation should not be diluted with distilled water. The solution should be diluted each time before use; the remaining 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 administered using various commercial models of nebulizers.The dose reaching the lungs and the systemic dose depend on the type of nebulizer used and may be higher than the corresponding doses using a metered dose aerosol (which depends on the type of inhaler). There is wall oxygen, 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. Aerosol for inhalation dosed The dose is set individually. To relieve attacks, adults and children over 6 years of age are prescribed 2 inhalation doses. If breathing relief does not occur within 5 minutes, 2 more inhalation doses can be prescribed. The patient should be informed to immediately consult a doctor if there is no effect after 4 inhalation doses and the need for additional inhalations. Metered-dose aerosol should be used in children only as prescribed by a doctor and under the supervision of adults. For long-term and intermittent therapy, 1-2 inhalations are prescribed per dose, up to 8 inhalations/day (on average, 1-2 inhalations 3 times/day). For bronchial asthma, the drug should be used only as needed. Rules for using the drug The patient should be instructed on the correct use of the metered-dose aerosol. Before using the metered-dose aerosol for the first time, press the bottom of the can twice. Each time you use a metered dose aerosol, the following rules must be observed. 1. Remove the protective cap. 2. Take a slow, deep breath. 3. Holding the balloon, wrap your lips around the mouthpiece. The cylinder should be pointing upside down. 4. While inhaling as deeply as possible, simultaneously quickly press the bottom of the cylinder until 1 inhalation dose is released. Hold your breath for a few seconds, then remove the mouthpiece from your mouth and exhale slowly. Repeat steps to receive the 2nd 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 cylinder is designed for 200 inhalations. Then the cylinder should be replaced. Although some contents may remain in the canister, the amount of drug released during inhalation is reduced. Since the balloon is opaque, the amount of drug in the balloon can be determined as follows: by removing the plastic mouthpiece from the balloon, the balloon is immersed in a container filled with water. The amount of the drug is determined depending on the position of the cylinder in the water. You should clean your inhaler at least once a week. It is important to keep the inhaler mouthpiece clean so that drug particles do not block the release of the aerosol. During cleaning, first remove the protective cap and remove the balloon from the inhaler. A stream of warm water is passed through the inhaler; You must ensure that the drug and/or visible dirt is removed. After cleaning, shake the inhaler and allow it to air dry without using heating devices. Once the mouthpiece is dry, insert the balloon into the inhaler and put on the protective cap. The contents of the cylinder are under pressure. The cylinder must not be opened or exposed to temperatures above 50°C.
Interaction
The simultaneous use of other beta-agonists, anticholinergic drugs and xanthine derivatives (for example, theophylline) may enhance the bronchodilator effect of the drug. A significant weakening of the bronchodilator effect of the drug is possible with the simultaneous administration of beta-blockers. Hypokalemia associated with the use of beta-agonists may be exacerbated by the simultaneous use of xanthine derivatives, corticosteroids and diuretics. This fact should be given special attention when treating patients with severe forms of obstructive airway diseases. Hypokalemia may lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia may enhance the negative effects of hypokalemia on heart rate. In such cases, it is recommended to monitor serum potassium concentrations. Beta2-agonists should be prescribed with caution to patients receiving MAO inhibitors and tricyclic antidepressants, because these drugs can enhance the effect of beta-adrenergic drugs. The use of inhaled halogenated anesthetics, such as halothane, trichlorethylene or enflurane, may increase the cardiovascular effects of beta-adrenergic agents. Combined use of the drug with cromoglycic acid and/or GCS increases the effectiveness of therapy.
Side effect
The frequency of adverse reactions was determined in accordance with WHO recommendations: very often (>1/10); often (>1/100, 1/1000, 1/10,000, From the immune system: rarely - hypersensitivity reactions, anaphylactic reactions. From metabolism and nutrition: rarely - hypokalemia, metabolic acidosis. Mental disorders: - infrequently - nervousness ; - rarely - anxiety, mental disorders. From the nervous system: infrequently - headache, dizziness, tremor. From the organ of vision: rarely - glaucoma, increased intraocular pressure, accommodation disturbances, mydriasis, blurred vision, pain in the eyes, swelling cornea, conjunctival hyperemia, the appearance of a halo around objects and colored spots before the eyes. From 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, dry throat. From the digestive system: - infrequently - vomiting, dry mouth, nausea; - rarely - stomatitis, glossitis, gastrointestinal motility disorders, constipation, diarrhea, swelling of the oral cavity. Dermatological reactions: rarely - urticaria, skin rash, itching, angioedema, hyperhidrosis. From the musculoskeletal system: rarely - muscle weakness, myalgia, muscle spasm. From the urinary system: rarely - urinary retention.
Contraindications
Hypertrophic obstructive cardiomyopathy;
tachyarrhythmia; I and III trimesters of pregnancy; children under 6 years of age (aerosol for inhalation); hypersensitivity to fenoterol and other components of the drug; hypersensitivity to atropine-like drugs. With caution: angle-closure glaucoma, arterial hypertension, diabetes mellitus, recent myocardial infarction (within the last 3 months), heart and vascular diseases (chronic heart failure, coronary artery disease, arrhythmia, aortic stenosis, severe lesions of the cerebral and peripheral arteries), hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, cystic fibrosis, second trimester of pregnancy, lactation period, childhood and adolescence from 6 to 18 years (aerosol for inhalation). Use during pregnancy and lactation Data from preclinical studies and experience with the combination of ipratropium bromide and fenoterol show that the components of the drug do not have a negative effect during pregnancy. The possibility of an inhibitory effect of fenoterol on uterine contractility should be taken into account. The drug is contraindicated in the first and third trimesters of pregnancy (the possibility of weakening labor by fenoterol). The drug should be used with caution in the second trimester of pregnancy. Fenoterol is excreted in breast milk. There is no data confirming that ipratropium bromide passes into breast milk. The use of the drug during breastfeeding is possible only if the potential benefit to the mother outweighs the potential risk to the child.
special instructions
The patient should be informed that if shortness of breath (difficulty breathing) suddenly increases rapidly, consult a doctor immediately. Paradoxical bronchospasm The drug can cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm develops, the use of the drug should be stopped immediately and switched to alternative therapy. Long-term use In patients with bronchial asthma, the drug should be used only as needed. In patients with mild COPD, symptomatic treatment may be preferable to regular use. In patients with bronchial asthma, one should remember the need to carry out or intensify 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 beta2-agonists to relieve bronchial obstruction can cause uncontrolled worsening of the disease. In case of increased bronchial obstruction, increasing the dose of beta2-agonists more than recommended for a long time is not only not justified, but also dangerous. To prevent life-threatening worsening of the disease, consideration should be given to reviewing the patient's treatment plan and adequate anti-inflammatory therapy with inhaled corticosteroids. Other sympathomimetic bronchodilators should be co-administered with the drug only under medical supervision. Visual disorders The drug should be prescribed with caution to patients predisposed to the development of angle-closure glaucoma. There are isolated reports of complications from the organ of vision (for example, increased intraocular pressure, mydriasis, angle-closure glaucoma, eye pain) that developed when inhaled ipratropium bromide (or ipratropium bromide in combination with β2-adrenergic receptor agonists) entered the eyes. Symptoms of acute angle-closure glaucoma may include pain or discomfort in the eyes, blurred vision, the appearance of a halo on objects and colored spots in front of the eyes in combination with corneal edema and redness of the eyes due to conjunctival vascular injection. If any combination of these symptoms is observed, the use of eye drops that reduce intraocular pressure and immediate consultation with a specialist is indicated. Patients should be instructed on the correct use of the inhalation solution. To prevent the solution from getting into the eyes, it is recommended that the solution used with a nebulizer be inhaled through the mouthpiece. If you do not have a mouthpiece, use a mask that fits tightly to your face. Particular care should be taken to protect the eyes of patients predisposed to the development of glaucoma. Systemic effects In diseases such as recent myocardial infarction, diabetes mellitus with inadequate glycemic control, severe organic heart and vascular diseases, hyperthyroidism, pheochromocytoma or urinary tract obstruction (for example, prostatic hyperplasia or bladder neck obstruction), the drug should be prescribe only after a careful assessment of the risk/benefit ratio, especially when used in doses higher than recommended. Effect on the cardiovascular system In post-marketing studies, rare cases of myocardial ischemia have been reported when taking beta-adrenergic agonists. Patients with underlying serious heart disease (eg, coronary artery disease, arrhythmias, or significant heart failure) receiving the drug should be warned to seek medical attention if heart pain or other symptoms indicating worsening of heart disease occur. It is necessary to pay attention to symptoms such as shortness of breath and chest pain, because... they can be of both cardiac and pulmonary etiology. Hypokalemia Hypokalemia may occur when using β2-adrenergic receptor agonists. In athletes, the use of the drug, due to the presence of fenoterol in its composition, can lead to positive doping test results. Excipients The drug in the form of an aerosol for inhalation contains a preservative, benzalkonium chloride, and a stabilizer - disodium edetate dihydrate. During inhalation, these components may cause bronchospasm in sensitive patients with airway hyperresponsiveness. Effect on the ability to drive vehicles and use machines The effect of the drug on the ability to drive vehicles and use machines has not been specifically studied. However, patients should be informed that during treatment with the drug, the development of such undesirable effects as dizziness, tremor, impaired accommodation, mydriasis, and blurred vision is possible. Therefore, caution should be recommended when driving vehicles or using machinery. If patients experience the above unwanted sensations, they should refrain from potentially dangerous activities such as driving vehicles or operating machinery.
Storage conditions
Room temperature
Dispensing conditions in pharmacies
On prescription
Special instructions
If shortness of breath (difficulty breathing) suddenly increases rapidly, you should consult a doctor immediately.
In children, the drug should be used only as prescribed by a doctor and under the supervision of adults.
In athletes, the use of the drug Ipraterol-native due to the presence of fenoterol in its composition can lead to positive results of doping tests.
Patients should be instructed on the correct use of Ipraterol-native inhalation solution. To prevent the solution from getting into the eyes, it is recommended that the solution used with a nebulizer be inhaled through the mouthpiece. If there is no mouthpiece, a mask that fits tightly to the face should be used. Patients predisposed to developing glaucoma should take special care to protect their eyes.
No studies have been conducted to study the effect of the drug on the ability to drive vehicles and operate machinery. Cases of dizziness and blurred vision while using the drug may have a negative impact on the above-mentioned ability.
High-quality generics for the treatment of broncho-obstructive diseases: there is light at the end of the tunnel!
Acute and chronic respiratory diseases in the Russian Federation account for about 40% of the total morbidity rate of the country's population (including acute respiratory diseases), while for the period 2000–2008. incidence rates did not fall below 290 cases per 1000 people.
Among respiratory diseases, bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) predominate. According to experts, the number of patients with asthma is at least 5–6 times higher than official statistics (5.9 million people compared to reported data - 1.3 million people). It has been established that patients suffering from asthma are often disabled. Thus, in Moscow, 41% of patients with asthma receive disability benefits [1].
In the Russian Federation, direct healthcare costs associated with the treatment of asthma amount to about 8.5 billion rubles, of which 66.6% is spent on inpatient treatment, 21.5% on the purchase of medicines, 10.9% on outpatient treatment , 0.9% - for ambulance calls.
In the structure of indirect costs for asthma (about 2.8 billion rubles), the cost of paying for certificates of incapacity for work is 61.4%, disability benefits - 27.3%, the lost contribution to the gross domestic product due to exacerbation of the disease with a certificate of incapacity for work - 11 ,4%.
The total (direct and indirect) costs associated with asthma are about 0.75% of the entire healthcare budget of the Russian Federation [1].
Noteworthy is the fact that the costs of medicines are extremely insufficient and in the overall structure of treatment costs they amount to only 11.0%. Per one patient with asthma, this amounts to 1,418.2 rubles per year.
In this regard, the introduction into practice of new medicinal technologies, the use of which will reduce the burden of the disease and budget costs, is of extreme interest.
According to the modern concept of the World Health Organization (WHO), generic drugs have numerous public health benefits, primarily associated with the affordable price of the drug.
However, the use of a generic drug instead of the original one can be justified only if the doctor is convinced that this will not reduce the effectiveness of treatment and, moreover, will not threaten the patient’s life. In Russia, where most generics and/or substances for their production are produced in developing countries of the Asian region, the problem of the quality of such drugs is especially acute. In addition, the complexity of solving this problem is aggravated by the fact that modern inhaled drugs use high-tech devices as delivery vehicles, the reproduction and production of which requires special efforts and large capital investments.
To establish the equivalence of inhaled drugs, at least 5 steps must be taken [2]:
1) confirmation of the equivalence of the qualitative and quantitative composition of the main and auxiliary substances;
2) establishing the similarity of the delivery vehicles used;
3) assessment of the properties of the inhaler in vitro, including assessment of the particle size of the inhaled dose;
4) study of the pulmonary distribution and systemic pharmacokinetics of the drug in vivo;
5) evidence of similarity in therapeutic effectiveness.
Unfortunately, generic inhaled drugs appearing on the Russian pharmaceutical market are not always fully equivalent to the original drugs.
Thus, L. A. Trukhacheva et al. [3] when studying the degree of equivalence of inhaled fractions on a 7-stage cascade impactor of the new generation Next (Copley Scientific Limited England) for metered-dose aerosol inhalers Seretide, 25/250 (salmeterol xinafoate/fluticasone propionate) mcg/dose, manufactured by GlaxoSmithKline Pharmaceuticals, Poland, and Tevacomb, 25/250 (salmeterol xinafoate/fluticasone propionate) mcg/dose, manufactured by Cipla Ltd., India, established statistical differences in determining such significant parameters as the mass median aerodynamic diameter of particles and the geometric standard deviation from the mass median aerodynamic diameter, as well as the values of the fraction of fine particles (FMP) and the value of the released dose. For salmeterol xinafoate, the FMC values were 42.06% (Seretide) and 35.53% (Tevacomb), respectively, for fluticasone propionate - 42.94% (Seretide) and 35.44% (Tevacomb).
Previously, we established that the reproduced drug mentioned above differs from the original one in the amount of impurities it contains. Despite the fact that both drugs met the stated requirements of regulatory documentation, the amount of impurities of fluticasone propionate in the generic was at the upper limit of the permissible norm (no more than 0.4%) and amounted to 0.385%. In addition, trace amounts of bromine (0.7 ppm) were found in Tevacombe, the presence of which is not generally assumed by the current regulatory documentation [4].
In connection with the above, great hopes are placed on new domestic developments in the field of asthma treatment, which, in particular, is being dealt with. Currently, the company has developed a whole line of generic inhaled drugs using modern delivery vehicles, the properties of which have been thoroughly studied in laboratory and clinical studies.
One of the studies was devoted to the study of the aerodynamic characteristics of the drug Beclomethasone-aeronativ, a dosed aerosol for inhalation produced by Nativa LLC (Russia) in comparison with the drugs Beclazon Eco, 250 mcg/dose, produced by Norton Waterford (Ireland) and Clenil, 250 mcg /dose, produced by Chiesi Pharmaceuticals S.p.A. (Italy), in which indicators such as dosing uniformity and the size of the respirable fraction were assessed using the Andersen cascade impactor.
The results of the studies are given in table. 1.
Thus, as follows from the above data, the drug Beclomethasone-aeronativ produced by Nativa LLC (Russia) in comparison with the drugs Beclazon Eco 250 mcg/dose, produced by Norton Waterford (Ireland) and Clenil 250 mcg/dose (Chiesi Pharmaceuticals S.p.A., Italy) demonstrate comparable results in terms of dosage uniformity and respirable fraction.
The next study was devoted to assessing the aerodynamic characteristics of the drug Ipraterol-native, solution for inhalation 0.25 mg/ml + 0.5 mg/ml (ipratropium bromide + fenoterol). The proportion of small particles can vary significantly when using devices from different manufacturers and different models. In addition, the respirable fraction may depend on the viscosity of the drug medium and on its prior dilution, for example, with saline or when mixed with another drug.
A comparison of the compositions of the generic and the original drug showed that the qualitative composition of the drugs differs only in one of the preservatives: benzalkonium chloride in Ipraterol-native was replaced by sodium benzoate (Table 2).
The respirable fraction as a percentage was determined as the ratio of the sum of the masses of particles deposited on cascades 2 to 7 to the sum of the masses of all cascades and the L-shaped tube.
The results of the studies are presented in Fig. 1–4.
Thus, the drugs Ipraterol-Nativ (Nativa LLC) and Berodual (Boehringer Ingelheim) in the form of nebulization solutions during comparative aerodynamic tests showed complete identity in the size of the respirable fraction and particle size distribution profiles.
Two more similar studies were devoted to the study of the aerodynamic properties of the drug Saltikazon-native (Nativa LLC, Russia) in comparison with the drug Seretide Multidisc (Glaxo Operations UK Ltd., UK) and the drug Formisonide-native (Nativa LLC, Russia ) in comparison with the drug Symbicort Turbuhaler (AstraZeneca, UK)2. The design of the mentioned studies was similar to previous ones.
It is gratifying to note that according to the results of the studies mentioned above, both generic drugs demonstrated comparable results in terms of dosage uniformity and respirable fraction in relation to the original ones.
So, the currently available evidence of the comparability of the quality characteristics of generics in relation to well-known original drugs allows us to hope that a worthy replacement for expensive imported drugs has appeared on the Russian pharmaceutical market, providing equivalent effectiveness and safety profile in patients with broncho-obstructive diseases.
Literature
- Socio-economic losses from bronchial asthma and chronic obstructive pulmonary disease in the Russian Federation. Consolidated report. M.: RBOF “Quality of Life”. 125 pp.
- Daley-Yates PT, Parkins DA Establishing bioequivalence for inhaled drugs; weighing the evidence // Expert Opin. Drug Deliv. 2011; 1:112.
- Trukhacheva L. A., Gorpinchenko N. V., Dementyev S. P. Comparative in vitro study of the equivalence of metered-dose aerosol inhalers Seretide and Tevacomb using a new generation Next impactor // Clinical pharmacology and therapy. 2012. No. 21 (4). pp. 73–77.
- Zyryanov S.K., Aisanov Z.R. Reproduced inhalation drugs: how to evaluate their properties? // Pulmonology. 2012. No. 3. pp. 115–118.
S. K. Zyryanov, Doctor of Medical Sciences, Professor Zh. A. Galeeva1, Candidate of Medical Sciences Yu. B. Belousov, Doctor of Medical Sciences, Professor
GBOU VPO RNIMU im. N. I. Pirogova Ministry of Health of the Russian Federation, Moscow
1 Contact information
2 The drugs Saltikazon-native and Formisonide-native are not registered in the Russian Federation. There are permissions to conduct clinical trials of these drugs. Currently, the research status is “Completed”.
