Ipraterol-Nativ solution for inhalation 0.25mg/ml+0.5mg/ml, dropper bottle 20ml 1pc

Composition

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1 ml of the solution contains:

Active ingredient:  

ipratropium bromide monohydrate;

Auxiliary substances:  

sodium benzoate 0.5 mg,

disodium edetate 0.5 mg,

citric acid monohydrate 1.5 mg,

sodium hydroxide up to pH 3.2, water d / i up to 1 ml

Pharmacological action

Ipraterol-native contains two components with bronchodilatory activity: ipratropium bromide-m-holinoblokator and fenoterol-β2-adrenomimetic. Bronchodilation during inhaled use of ipratropium bromide is mainly due to local, rather than systemic, anticholinergic effects.

In patients with bronchospasm associated with chronic obstructive pulmonary diseases (chronic bronchitis and emphysema), a significant improvement in lung function (an increase in FEV 1 and PSV by 15% or more) was noted within 15 minutes, the maximum effect was achieved in 1-2 hours and lasted in most patients up to 6 hours after use.

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

Fenoterol selectively stimulates beta-2-adrenergic receptors at a therapeutic dose. Beta-2-adrenergic receptors are stimulated when high doses are used. 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 use, fenoterol blocks the release of inflammatory mediators and bronchial obstruction from mast cells. In addition, when using fenoterol in higher doses, there was an increase in mucociliary clearance.

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 effect of fenoterol, stimulation of beta-2-adrenergic receptors of the heart, and when using doses higher than therapeutic, stimulation of beta-1-adrenergic receptors.

As with other beta-adrenergic drugs, QTC interval prolongation was observed when using high doses. The clinical significance of this manifestation has not been clarified.

Tremor is the most common undesirable effect when using beta-adrenergic agonists.

When these two active substances 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 increases and the breadth of therapeutic action is provided for bronchopulmonary diseases accompanied by airway constriction.

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 almost complete absence of side effects.

Pharmacokinetics

There is no evidence that the pharmacokinetics of the combined drug differ from those of each of the individual components.

Suction

Ipratropium bromide. With the inhaled route of use, ipratropium bromide is characterized by extremely low absorption from the respiratory mucosa. The concentration of the Active ingredient in plasma is at the lower limit of determination, and it can be measured only with the use of high doses of the Active ingredient, as well as through the use of specific enrichment methods.

When inhaled at therapeutic doses, plasma concentrations of ipratropium bromide were 1000 times lower than after oral and intravenous use.

Fenoterol.

Depending on the method of inhalation and the inhalation system used, about 10-30% of the Active ingredient reaches the lower respiratory tract, and the rest is deposited in the upper respiratory tract and swallowed. As a result, a certain amount of 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 pharmacodynamic time-effect curve.

The long-term bronchodilator effect of the drug after inhalation, comparable to the corresponding effect achieved after intravenous use, is not supported by high concentrations of the Active ingredient in the systemic circulation. After oral use, about 60% of fenoterol is absorbed. The time to reach the maximum concentration in blood plasma is 2 hours.

Distribution

Ipratropium bromide. Being a quaternary nitrogen derivative, it is poorly soluble in fats and weakly penetrates biological membranes. It doesn’t accumulate.

Fenoterol. Binding to plasma proteins is 40-55%. Fenoterol in unchanged form penetrates 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 intravenous dose and 35% of the oral dose are excreted in the urine. This proportion of the Active ingredient undergoes biotransformation due to the” primary passage effect ” through the liver, as a result of which the bioavailability of the drug after oral use decreases to approximately 1.5%.

This explains the fact that the ingested amount of the drug practically does not affect the level of the Active ingredient in the blood plasma reached after inhalation. Biotransformation of fenoterol in humans occurs exclusively by conjugation with sulfates mainly in the intestinal wall.

Deduction

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 bile in the form of inactive sulfate conjugates. When parenterally administered, fenoterol is excreted in a three – phase model with half-lives of 0.42 minutes,14.3 minutes and 3.2 hours, respectively.

The pharmacokinetics of the combination of ipratropium bromide and fenoterol in the elderly and pediatric population, as well as in patients with impaired liver and kidney function, have not been studied.

Indications

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 Ipraterol-native;
• hypertrophic obstructive cardiomyopathy;

• tachyarrhythmia;

• I and III trimesters of pregnancy.

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

Side effects

Nervous system disorders:  often-a small tremor of skeletal muscles, nervousness; rarely-headache, dizziness, very rarely-a change in the psyche.

From the cardiovascular system:  often-tachycardia, including supraventricular tachycardia; palpitation (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).

Respiratory system disorders:  rarely-cough, local irritation of the respiratory tract, pharyngitis; very rarely-paradoxical bronchospasm, laryngospasm.

From the gastrointestinal tract:  often – dry mouth; infrequently-impaired gastrointestinal motility, vomiting, constipation, diarrhea (especially in patients with cystic fibrosis).

From the side of the visual organ:  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 in front of the eyes, combined with conjunctival hyperemia and corneal edema can be symptoms of acute glaucoma. Use pupil-constricting drops and immediately consult an ophthalmologist.

Allergic reactions:  rarely – skin rash, angioedema of the tongue, lips and face, urticaria.

Other services:  urinary retention, increased sweating, hypokalemia, feeling of general weakness, myalgia.

Interaction

Concomitant use of other beta-adrenomimetic agents, systemic anticholinergic drugs and xanthine derivatives (for example, theophylline) may increase the bronchodilator effect of Ipraterol-native.

It is possible to significantly weaken the bronchodilator effect of the drug with simultaneous use of beta-adrenoblockatorone.

Hypokalemia associated with the use of beta-adrenomimetics may be increased by concomitant use of xanthine derivatives, glucocorticosteroids, and diuretics. This fact should be given special attention in the treatment of patients with severe obstructive airway diseases.

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

Caution should be exercised when prescribing rg-adrenergic agents to patients treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these drugs can enhance the effect of beta-adrenergic agents. General anaesthetic inhalation of halogenated hydrocarbon anaesthetics, such as halothane, tri-chloroethylene or enflurane, may increase the effect of beta-adrenergic agents on the cardiovascular system.

The combined use of Ipraterol-native with Cromoglicic acid and / or glucocorticosteroids increases the effectiveness of therapy.

How to take, course of use and dosage

The dose should be selected individually. Medical supervision is required during therapy. The following doses are recommended:

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

Acute attacks of bronchial asthma

For mild to moderate seizures,1 ml (20 drops) is recommended in many cases. In particularly severe cases, such as 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 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,1-2 ml (20-40 drops) is used for each use up to 4 times a day.

In the case of moderate bronchospasm or as an adjunct to lung ventilation, a dose with a lower level of 0.5 ml (10 drops) is recommended.

For 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 particularly severe cases, if a dose of up to 2.0 ml (40 drops) is ineffective, a maximum dose of up to 3.0 ml (60 drops) may be used (subject to medical supervision).

The maximum daily dose can reach 4.0 ml (80 drops).

Course and long-term treatment

If necessary, repeated use is used for each use of 0.5-1 ml (10-20 drops) up to 4 times a day.

In cases of moderate bronchospasm or as an adjunct to lung ventilation, the recommended dose is 0.5 ml (10 drops).

In children under 6 years of age (with a body weight of less than 22 kg):

Due to the fact that information about the use of the drug in this age group is limited, it is recommended to use the following dose (only under medical supervision): about 25 mcg of ipratropium bromide and 50 mcg of fenoterol hydrobromide = 0.1 ml (2 drops) per kg of body weight (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 peroral.

Treatment should usually start with 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.

Dilution of the solution should be carried out every time before use, the remains of the diluted solution should be destroyed.

The diluted solution should be used immediately after cooking.

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 with various commercial models of nebulizers. In cases where wall-mounted oxygen is available, the solution is best applied at a flow rate of 6-8 liters per minute. Follow the instructions for use, maintenance, and cleaning of the device provided with the nebulizer.

Overdose

Symptoms of overdose are usually associated with the action of fenoterol. Symptoms associated with excessive beta-adrenergic stimulation may occur.

Most likely to occur are tachycardia, palpitations, tremors, increased blood pressure, increased differences between systolic and diastolic blood pressure, angina, arrhythmia and a feeling of” flushes ” of blood to the face, a feeling of heaviness behind the sternum, increased bronchial obstruction, and metabolic acidosis.

Possible overdose symptoms caused by ipratropium bromide (such as dry mouth, accommodation disorders) are mild and transient, which is explained by its local use.

Treatment: it is recommended to prescribe sedatives, anxiolytic drugs (tranquilizers), in severe cases – intensive care.

As a specific antidote, it is possible to use beta-blockers, preferably selective beta-1-blockers. However, in patients with asthma or COPD, the possibility of increased bronchial obstruction, which can lead to death under the influence of beta-blockers, should be considered and their dose should be carefully selected.

Special instructions

In case of sudden rapid increase in shortness of breath (difficulty breathing), you should immediately consult a doctor. Long-term use:

– in patients with bronchial asthma or mild to moderate forms of COPD, symptomatic treatment may be preferable to regular use;

– in patients with bronchial asthma or severe forms of COPD, you should be aware of the need to conduct or strengthen 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 beta-2-adrenomimetics, such as Ipraterol-native, to relieve bronchial obstruction may cause uncontrolled worsening of the course of the disease. In case of increased bronchial obstruction, increasing the dose of beta-2 agonists, including Ipraterol-native, more than the recommended dose 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 glucocorticosteroids. Patients with a history of cystic fibrosis may have gastrointestinal motility disorders.

Other sympathomimetic bronchodilators should be administered simultaneously with Ipraterol-native only under medical supervision. Patients should be instructed on the correct use of the inhaled solution of Ipraterol-native.

To prevent the solution from getting into the eyes, it is recommended that the solution used with the nebulizer be inhaled through the mouthpiece. In the absence of a mouthpiece, a face mask that fits snugly should be used. Patients predisposed to developing glaucoma should take special care to protect their eyes.

Influence on the ability to drive motor vehicles and manage mechanisms

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

Active ingredient

Ipratropium bromide, Fenoterol

Conditions of release from pharmacies

By prescription

Dosage form

solution for inhalation

Purpose

Pregnant women as prescribed by a doctor, Nursing mothers, Adults as prescribed by a doctor, Children as prescribed by a doctor

Indications

Bronchospasm, Bronchial Asthma, Low learning rate