Ipraterol - Nativ solution for inhalation, 20 ml

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

The dose should be adjusted individually. During therapy, medical supervision is required. The following doses are recommended:

In adults (including the elderly) and adolescents over 12 years of age:

Acute attacks of bronchial asthma
For mild to moderate attacks, in many cases, 1 ml (20 drops) is recommended.
In especially severe cases, for example, in patients in intensive care units, if the doses indicated above are ineffective, higher doses may be required, up to 2.5 ml (50 drops).
The maximum dose can be up to 4.0 ml (80 drops).
The maximum daily dose is 8.0 ml (160 drops).
Course and long-term treatment
If it is necessary to reuse for each injection, use 1-2 ml (20-40 drops) up to 4 times a day.
In the case of moderate bronchospasm or as an aid in the implementation of ventilation, a dose is recommended, the lower level of which is 0.5 ml (10 drops).

In children aged 6-12 years:

Acute attacks of bronchial asthma
In many cases, 0.5 - 1 ml (10 - 20 drops) is recommended for rapid relief of symptoms.
In severe cases, if a dose of 1 ml (20 drops) is ineffective, higher doses may be required, up to 2 ml (40 drops).
In especially 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 reaching 3.0 ml (60 drops).
The maximum daily dose can be up to 4.0 ml (80 drops).
Course and long-term treatment
If necessary, reuse is used for each injection of 0.5 - 1 ml (10 - 20 drops) up to 4 times a day.
In cases of moderate bronchospasm or as an aid in the implementation of ventilation, the recommended dose is 0.5 ml (10 drops).

In children under 6 years of age (weighing less than 22 kg):

Due to the fact that information on the use of the drug in this age group is limited, the use of the following dose is recommended (only subject to medical supervision):
about 25 ?g ipratropium bromide and 50 ?g fenoterol hydrobromide = 0.1 ml (2 drops) per kg of weight body (per dose), but not more than 0.5 ml (10 drops) (per dose).
The maximum daily dose is 1.5 ml.
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.
Ipraterol-native solution for inhalation should not be diluted with distilled water.
The dilution of the solution should be carried out each time before use, the remnants of the diluted solution should be destroyed.
The diluted solution should be used immediately after preparation.
Dosage may depend on the inhalation method 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 applied using various commercial models of nebulizers. Where wall oxygen is available, the solution is best applied at a flow rate of 6 to 8 liters per minute.
Follow the instructions for use, maintenance and cleaning of the device supplied with the nebulizer.

Active substance:

Fenoterol hydrobromide - 0.5 mg

Ipratropium bromide monohydrate - 0.261 mg

(in terms of ipratropium bromide) (0.25 mg)

Excipients:

Sodium benzoate - 0.5 mg

Sodium edetate - 0.5 mg

Citric acid monohydrate - 1.5 mg

Sodium hydroxide up to pH 3.2

Water for injection up to 1.0 ml

Ј Hypersensitivity to fenoterol or atropine-like drugs or other components of the drug Ipraterol-native.

Hypertrophic obstructive cardiomyopathy

Ј Tachyarrhythmia.

Ј I and III trimesters of pregnancy.

Carefully

Angle-closure glaucoma, arterial hypertension, diabetes mellitus, recent myocardial infarction (within the last 3 months), heart and vascular diseases such as chronic heart failure, ischemic heart disease, aortic stenosis, severe lesions of cerebral and peripheral arteries, hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, cystic fibrosis, II trimester of pregnancy, breastfeeding, children under 6 years of age.

Trade name of the drug:

Ipraterol-native

International non-proprietary or group name:

Ipratropium bromide + Fenoterol

Dosage form:

inhalation solution

Composition for 1 ml:

Active substance:

Fenoterol hydrobromide - 0.5 mg

Ipratropium bromide monohydrate - 0.261 mg

(in terms of ipratropium bromide) (0.25 mg)

Excipients:

Sodium benzoate - 0.5 mg

Sodium edetate - 0.5 mg

Citric acid monohydrate - 1.5 mg

Sodium hydroxide up to pH 3.2

Water for injection up to 1.0 ml

Description : clear, colorless or slightly yellowish liquid

Pharmacotherapeutic group:

combined bronchodilator (? 2-selective adrenomimetic + m-anticholinergic)

Pharmacological properties

Pharmacodynamics

Ipraterol-native contains two components with bronchodilator activity: ipratropium bromide - an m-anticholinergic antagonist and fenoterol - a 2-adrenergic agonist.
Bronchodilation with inhalation of ipratropium bromide is mainly due to local, rather than systemic, anticholinergic action. In patients with bronchospasm associated with chronic obstructive pulmonary diseases (chronic bronchitis and pulmonary emphysema), a significant improvement in lung function (an increase in FEV1 and PSV 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 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 in higher doses, 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 ?2-adrenergic receptors of the heart, and when using doses exceeding therapeutic ones, stimulation of ?1-adrenergic receptors. As with the use of other beta-adrenergic drugs, a prolongation of the QTc interval has been observed with the use of high doses. The clinical significance of this manifestation has not been clarified.
Tremor is the most common adverse effect when using beta-adrenergic agonists.
When these two active substances are used together, 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 breadth 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.

Pharmacokinetics

There is no evidence that the pharmacokinetics of the combination drug differs from that of each of the individual components.
Absorption
Ipratropium bromide. When inhaled, ipratropium bromide is characterized by extremely low absorption from the mucous membrane of the respiratory tract. The concentration of the active substance in the plasma is at the lower limit of determination, and it can be measured only with the use of high doses of the active substance, as well as through the use of specific enrichment methods. When inhaled at therapeutic doses, the plasma concentration of ipratropium bromide was 1000 times lower than after oral administration and intravenous administration.
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 rest is deposited in the upper respiratory tract and is swallowed. As a result, some of the inhaled fenoterol enters the gastrointestinal tract.
Absorption is biphasic - 30% of fenoterol is rapidly absorbed with a half-life of 11 minutes, 70% is absorbed slowly with a half-life of 120 minutes. There is no correlation between the plasma concentrations of fenoterol achieved after inhalation and the time-response pharmacodynamic curve. The long-term bronchodilatory effect of the drug after inhalation, comparable to the corresponding effect achieved after intravenous administration, is not supported by high concentrations of the active substance in the systemic circulation. After oral administration, about 60% of fenoterol is absorbed. The time to reach the maximum concentration in blood plasma is 2 hours.
Distribution of
Ipratropium bromide.Being a derivative of quaternary nitrogen, it is poorly soluble in fats and weakly penetrates biological membranes. Does not cumulate.
Fenoterol. Communication with plasma proteins 40-55%. Fenoterol in unchanged form crosses the placental barrier and is excreted in breast milk.
Metabolism
Ipratropium bromide. It is metabolized in the liver. Up to 8 metabolites of ipratropium are known to bind weakly to muscarinic receptors.
Fenoterol.It is metabolized in the liver. After 24 hours, 60% of the administered intravenous dose and 35% of the oral dose are excreted in the urine. This proportion of the active substance undergoes biotransformation due to the 'effect of primary passage' through the liver, as a result of which the bioavailability of the drug after oral administration drops to approximately 1.5%. This explains the fact that the swallowed amount of the drug has practically no effect on the level of the active substance in the blood plasma achieved after inhalation. Biotransformation of fenoterol in humans occurs exclusively by conjugation with sulfates, mainly in the intestinal wall.
Withdrawal of
ipratropium bromide. It is excreted mainly through the intestines. About 25% is excreted unchanged, the rest in the form of numerous metabolites.
Fenoterol. It is excreted by the kidneys and with bile in the form of inactive sulfate conjugates. When administered parenterally, fenoterol is excreted according to a three-phase model with half-lives of 0.42 minutes, 14.3 minutes and 3.2 hours.
The pharmacokinetics of the combination of ipratropium bromide and fenoterol in the population of the elderly and children, as well as in patients with impaired liver and kidney functions, has not been studied.

Indications for use

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

Contraindications

• Hypersensitivity to fenoterol or atropine-like drugs or other components of the Ipraterol-native drug.

• Hypertrophic obstructive cardiomyopathy

• Tachyarrhythmia.

• I and III trimesters of pregnancy.

Carefully

Angle-closure glaucoma, arterial hypertension, diabetes mellitus, recent myocardial infarction (within the last 3 months), heart and vascular diseases such as chronic heart failure, ischemic heart disease, aortic stenosis, severe lesions of cerebral and peripheral arteries, hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, cystic fibrosis, II trimester of pregnancy, breastfeeding, children under 6 years of age.

Application during pregnancy and during breastfeeding

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. Consideration should be given to the possibility of an inhibitory effect of fenoterol on the contractile activity of the uterus. The drug is contraindicated in the first and third trimesters of pregnancy (the possibility of weakening labor with fenoterol). The drug should be used with caution in the II trimester of pregnancy. Fenoterol passes into breast milk. There is no evidence that ipratropium bromide passes into breast milk. However, the drug Ipraterol-native should be used with caution in nursing mothers.

Method of administration and dosage

The dose should be adjusted individually. During therapy, medical supervision is required. The following doses are recommended:

In adults (including the elderly) and adolescents over 12 years of age:

Acute attacks of bronchial asthma
For mild to moderate attacks, in many cases, 1 ml (20 drops) is recommended.
In especially severe cases, for example, in patients in intensive care units, if the doses indicated above are ineffective, higher doses may be required, up to 2.5 ml (50 drops).
The maximum dose can be up to 4.0 ml (80 drops).
The maximum daily dose is 8.0 ml (160 drops).
Course and long-term treatment
If it is necessary to reuse for each injection, use 1-2 ml (20-40 drops) up to 4 times a day.
In the case of moderate bronchospasm or as an aid in the implementation of ventilation, a dose is recommended, the lower level of which is 0.5 ml (10 drops).

In children aged 6-12 years:

Acute attacks of bronchial asthma
In many cases, 0.5 - 1 ml (10 - 20 drops) is recommended for rapid relief of symptoms.
In severe cases, if a dose of 1 ml (20 drops) is ineffective, higher doses may be required, up to 2 ml (40 drops).
In especially 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 reaching 3.0 ml (60 drops).
The maximum daily dose can be up to 4.0 ml (80 drops).
Course and long-term treatment
If necessary, reuse is used for each injection of 0.5 - 1 ml (10 - 20 drops) up to 4 times a day.
In cases of moderate bronchospasm or as an aid in the implementation of ventilation, the recommended dose is 0.5 ml (10 drops).

In children under 6 years of age (weighing less than 22 kg):

Due to the fact that information on the use of the drug in this age group is limited, the use of the following dose is recommended (only subject to medical supervision):
about 25 ?g ipratropium bromide and 50 ?g fenoterol hydrobromide = 0.1 ml (2 drops) per kg of weight body (per dose), but not more than 0.5 ml (10 drops) (per dose).
The maximum daily dose is 1.5 ml.
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.
Ipraterol-native solution for inhalation should not be diluted with distilled water.
The dilution of the solution should be carried out each time before use, the remnants of the diluted solution should be destroyed.
The diluted solution should be used immediately after preparation.
Dosage may depend on the inhalation method 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 applied using various commercial models of nebulizers. Where wall oxygen is available, the solution is best applied at a flow rate of 6 to 8 liters per minute.
Follow the instructions for use, maintenance and cleaning of the device supplied with the nebulizer.

Side effect

Determination of frequency: very often (> 1/10), often (from 1/100 to 1/10), infrequently (from 1/1000 to 1/100), rarely (from 1/10000 to 1/000), very rarely (
On the part of the nervous system: often - a small tremor of skeletal muscles, nervousness; rarely - headache, dizziness, very rarely - a change in the psyche.
On the part of the cardiovascular system: often - tachycardia, including supraventricular tachycardia; palpitations (especially in patients with aggravating factors); rarely (when used in high doses) - a decrease in diastolic blood pressure, an increase in systolic blood pressure, arrhythmia (including atrial fibrillation)
.From the respiratory system: rarely - cough, local irritation of the respiratory tract, pharyngitis; very rarely - paradoxical bronchospasm, laryngospasm.
From the gastrointestinal tract: often - dry mouth; infrequently - impaired motility of the gastrointestinal tract, vomiting, constipation, diarrhea (especially in patients with cystic fibrosis).
From the side of the organ of vision: if the drug gets into the eye - mydriasis, increased intraocular pressure, glaucoma, pain in the eyeball; sometimes during treatment with the drug, reversible accommodation disorders and glaucoma are noted. Pain in the eyeball or discomfort, blurred vision, a feeling of a halo or colored spots before the eyes, in combination with conjunctival hyperemia and corneal edema can be symptoms of acute glaucoma. Pupil-narrowing drops should be used and an ophthalmologist should be consulted immediately.
Allergic reactions: rarely - skin rash, angioedema of the tongue, lips and face, urticaria.
Others: urinary retention, increased sweating, hypokalemia, a feeling of general weakness, myalgia.

Overdose

—имптомы передозировани¤ обычно св¤заны с действием фенотерола. ¬озможно по¤вление симптомов, св¤занных с избыточной стимул¤цией бета-адренорецепторов. Ќаиболее веро¤тно по¤вление тахикардии, сердцебиени¤, тремора, повышени¤ артериального давлени¤, увеличени¤ различи¤ между систолическим и диастолическим артериальным давлением, стенокардии, аритмии и чувства Ђприливовї крови к лицу, чувство т¤жести за грудиной, усиление бронхообструкции, метаболического ацидоза. ¬озможные симптомы передозировки, обусловленные ипратропи¤ бромидом (такие как, сухость во рту, нарушение аккомодации), выражены слабо и транзиторно, что объ¤сн¤етс¤ его местным применением.
Ћечение: рекомендуетс¤ назначение седативных средств, анксиолитических лекарственных препаратов (транквилизаторов), в т¤желых случа¤х - интенсивна¤ терапи¤.
¬ качестве специфического антидота возможно применение бета-адреноблокаторов, предпочтительнее селективных ?1-адреноблокаторов. ќднако у пациентов с бронхиальной астмой или ’ќЅЋ следует учитывать возможность усилени¤ бронхиальной обструкции, котора¤ может привести к летальному исходу под вли¤нием бета-адреноблокаторов и тщательно подбирать их дозу.

¬заимодействие с другими лекарственными препаратами

ќдновременное применение других бета-адреномиметических средств, антихолинергических препаратов системного действи¤ и ксантиновых производных (например, теофиллина) могут усиливать бронхорасшир¤ющее действие препарата »пратерол-натив.
¬озможно значительное ослабление бронхорасшир¤ющего действи¤ препарата при одновременном назначении бета-адреноблокаторов.
vипокалиеми¤, св¤занна¤ с применением бета-адреномиметиков, может быть усилена одновременным назначением ксантиновых производных, глюкокортикостероидов и диуретиков. Ётому факту следует удел¤ть особое внимание при лечении пациентов с т¤желыми формами обструктивных заболеваний дыхательных путей. vипокалиеми¤ может приводить к повышению риска возникновени¤ аритмий у пациентов, получающих дигоксин.  роме того, гипокси¤ может усиливать негативное вли¤ние гипокалиемии на сердечный ритм. ¬ подобных случа¤х рекомендуетс¤ проводить мониторирование уровн¤ кали¤ в сыворотке крови.
—ледует с осторожностью назначать ?2-адренергические средства пациентам, получавшим ингибиторы моноаминооксидазы и трициклические антидепрессанты, так как эти препараты способны усилить действие бета-адренергических средств.
»нгал¤ци¤ средств дл¤ общей анестезии галогенизированных углеводородных анестетиков, например, галотана, трихлорэтилена или энфлурана, могут усилить вли¤ние бета-адренергических средств на сердечно-сосудистую систему.
—овместное применение препарата »пратерол-натив с кромоглициевой кислотой и/или глюкокортикостероидами увеличивает эффективность терапии.

ќсобые указани¤

¬ случае неожиданного быстрого усилени¤ одышки (затруднений дыхани¤) следует без промедлени¤ обратитьс¤ к врачу.
?лительное применение:
- у пациентов, страдающих бронхиальной астмой или легкой и среднет¤желой формами ’ќЅЋ, симптоматическое лечение может оказатьс¤ предпочтительнее регул¤рного применени¤;
- у пациентов с бронхиальной астмой или т¤желыми формами ’ќЅЋ следует помнить о необходимости проведени¤ или усилени¤ противовоспалительной терапии дл¤ контрол¤ воспалительного процесса дыхательных путей и течени¤ заболевани¤.
–егул¤рное использование возрастающих доз препаратов, содержащих ?2-адреномиметики, таких как препарат »пратерол-натив, дл¤ купировани¤ бронхиальной обструкции может вызвать неконтролируемое ухудшение течени¤ заболевани¤. ¬ случае усилени¤ бронхиальной обструкции увеличение дозы ?2-агонистов, в том числе препарата »пратерол-натив, больше рекомендуемой в течение длительного времени не только не оправдано, но и опасно. ?л¤ предотвращени¤ угрожающего жизни ухудшени¤ течени¤ заболевани¤ следует рассмотреть вопрос о пересмотре плана лечени¤ пациента и адекватной противовоспалительной терапии ингал¤ционными глюкокортикостероидами. ” пациентов, имеющих в анамнезе муковисцидоз, возможны нарушени¤ моторики желудочно-кишечного тракта.
?ругие симпатомиметические бронходилататоры следует назначать одновременно с препаратом »пратерол-натив только под медицинским наблюдением.
ѕациенты должны быть проинструктированы о правильном применении ингал¤ционного раствора препарата »пратерол-натив. ?л¤ предупреждени¤ попадани¤ раствора в глаза рекомендуетс¤, чтобы раствор, используемый с помощью небулайзера, вдыхалс¤ через мундштук. ѕри отсутствии мундштука должна использоватьс¤ плотно прилегающа¤ к лицу маска. ќсобенно тщательно должны заботитьс¤ о защите глаз пациенты, предрасположенные к развитию глаукомы.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

Studies to study the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. Cases of dizziness and blurred vision when using the drug can have a negative impact on the aforementioned ability.

Release form

Solution for inhalation 0.25 mg + 0.5 mg / ml. 20 ml of the drug in dark glass vials with a polyethylene dropper and a polypropylene screw cap.
1 bottle with instructions for use is placed in a cardboard box.

Storage conditions

In a dry, dark place at a temperature not exceeding 25 ? C.
Do not freeze.
Keep out of the reach of children.

Shelf life

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

Vacation conditions

Dispensed by prescription.