Ipraterol-native - instructions for use, dose, side effects, contraindications

Active substance:
Ipratropium bromide monohydrate	0.261 mg
(in terms of ipratropium bromide	0.25 mg)
Fenoterol hydrobromide	0.5 mg
Excipients:
Sodium benzoate	0.5 mg
Disodium edetate dihydrate	0.554 mg
Citric acid monohydrate	1.5 mg
Sodium hydroxide	to pH 3.2
Purified water	up to 1.0 ml

Description:

Transparent, colorless or with a yellowish tinge of liquid.

Pharmacotherapeutic group:Bronchodilator combined (beta2-adrenomimetic selective + m-holinoblokator)

ATX: & nbsp

R.03.A.L.01 Fenoterol and ipratropium bromide

Pharmacodynamics:

Ipraterol-native contains two components that have broncholytic activity: ipratropium bromide - m-holinoblokator and fenoterol - β₂-adrenomimetic.

Bronchodilation in the 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 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 in 1-2 hours and lasted in most patients up to 6 hours after administration.

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

Fenoterol selectively stimulates β₂-adrenoceptors in a therapeutic dose. Stimulation β₁-adrenoceptors occurs when high doses are used.

Fenoterol relaxes the smooth musculature of the bronchi and vessels and counteracts the development of bronchospastic reactions due to the influence of histamine, methacholine, cold air and allergens (immediate-type hypersensitivity reactions). Immediately after the introduction fenoterol blocks the release of mediators of inflammation and bronchoobstruction from mast cells. In addition, when fenoterol was used 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 heart rate and strength, is due to the vascular effect of fenoterol, stimulation of β₂β-adrenoreceptors of the heart, and when doses exceeding therapeutic are used, β₁adrenoreceptors. As with other beta-adrenergic drugs, lengthening of the interval QT_C when using high doses. The clinical significance of this manifestation is not clear.

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

When these two active substances are used together, the bronchodilating effect is achieved by affecting various pharmacological targets. These substances complement each other, as a result of increased spasmolytic effect on the muscles of the bronchi and provides a broad therapeutic effect for bronchopulmonary diseases, accompanied by constriction of the airways. Complementary action is such that to achieve the desired effect, a lower dose of beta-adrenergic component is required,which allows you to individually select the effective dose with almost no side effects.

Pharmacokinetics:

There is no evidence that the pharmacokinetics of the combined preparation is different from that of each of the individual components.

Suction

Ipratropium bromide. In inhalation administration, ipratropium bromide is characterized by extremely low absorption from the mucosa of the respiratory tract. The concentration of the active substance in the plasma is at the lower limit of the determination, and it can be measured only by applying high doses of the active substance, and also by using specific methods of enrichment. When inhaled in therapeutic doses, the concentrations of ipratropium bromide in plasma were 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 remainder is deposited in the upper respiratory tract and swallowed. As a result, some amount of inhaled fenoterol enters the gastrointestinal tract.Absorption is biphasic in nature - 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 plasma concentrations of fenoterol achieved after inhalation and the pharmacodynamic "time-effect" curve. The prolonged bronchodilator 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. Time to reach the maximum concentration in blood plasma - 2 hours.

Distribution

Ipratropium bromide. Being a derivative of quaternary nitrogen, it dissolves poorly in fats and weakly penetrates biological membranes. Do not cumulate.

Fenoterol. Relationship with plasma proteins 40-55%. Fenoterol in unchanged form penetrates the placental barrier and is excreted in breast milk.

Metabolism

Ipratropium bromide. Metabolised in the liver. It is known up to 8 metabolites of ipratropium, which bind weakly to muscarinic receptors.

Fenoterol. Metabolised in the liver. After 24 hours, 60% of the intravenously administered dose and 35% of the oral dose is excreted in the urine. This fraction of the active substance undergoes biotransformation due to the "primary pass effect" through the liver, as a result of which the bioavailability of the drug after oral administration drops to approximately 1.5%. This explains why the swallowed amount of the drug has practically no effect on the level of the active substance in the blood plasma, reached after inhalation. Biotransformation of fenoterol in humans occurs solely by conjugation with sulfates mainly in the intestinal wall.

Excretion

Ipratropium bromide. It is excreted mainly through the intestine. 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. With parenteral administration fenoterol respectively, a three-phase model with half-life periods of 0.42 minutes, 14.3 minutes and 3.2 hours, respectively.

The pharmacokinetics of the combination of ipratropium bromide and fenoterol in the population of elderly and children, as well as patients with impaired liver and kidney function has 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 emphysema.

Contraindications:

- Hypersensitivity to fenoterol or atropin-like drugs or other components of the preparation Ipraterol-native;

- hypertrophic obstructive cardiomyopathy;

- tachyarrhythmia;

- I and III trimesters of pregnancy.

Carefully:

Closed-angle 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 cerebral and peripheral arterial lesions, hyperthyroidism, pheochromocytoma, hyperplasia of the prostate, obstruction of the neck of the bladder, cystic fibrosis, second trimester of pregnancy, breastfeeding, children under 6 years.

Pregnancy and lactation:

Pre-clinical data and experience with the combination of ipratropium bromide and fenoterol indicate that the components of the drug do not adversely affect pregnancy. Consider the possibility of the inhibitory effect of fenoterol on contractile activity of the uterus. The drug is contraindicated in the I and III trimesters of pregnancy (the possibility of weakening the labor of fenoterol). It should be used with caution in the II trimester of pregnancy.

Fenoterol penetrates into breast milk. Data confirming that ipratropium bromide penetrates into breast milk, not received. However, the preparation of Ipraterol-native should be carefully administered to nursing mothers.

Dosing and Administration:

The dose should be selected individually. During the 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

In mild and 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 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 it is necessary to reuse, 1-2 ml (20-40 drops) are used for each injection up to 4 times a day.

In the case of moderate bronchospasm or as an aid in the implementation of ventilation, a dose of 0.5 ml (10 drops) is recommended.

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 the dose to 2.0 ml (40 drops) is ineffective, a maximum dose of up to 3.0 ml (60 drops) may be administered (subject to medical supervision).

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

Course and long-term treatment

If it is necessary to reuse, 0.5-1 ml (10-20 drops) up to 4 times a day.

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

In children under 6 years of age (body weight 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 μg of ipratropium bromide and 50 μg 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 be used only for inhalations (with a suitable nebulizer) and not to be used orally.

Treatment should usually begin 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 be applied (completely) with a nebulizer. The solution of Ipraterol-native for inhalations 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 preparation.

Dosage may depend on the inhalation method and the type of nebulizer.

The duration of inhalation can be controlled by the expenditure of diluted volume.

An ipraterol-native solution for inhalations can be used using various commercial models of nebulizers. In those cases where there is a wall oxygen, the solution is best used at a flow rate of 6-8 liters per minute.

Follow the instructions for use, maintenance and cleaning of the device supplied with the nebulizer.

Side effects:

Frequency determination: 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 (<1/10000).

From the nervous system: often - 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; sensation of palpitation (especially in patients with aggravating factors); rarely (when used in high doses) - reduced diastolic blood pressure, increased 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 - a violation of the motility of the gastrointestinal tract, vomiting, constipation, diarrhea (especially in patients with cystic fibrosis).

From the side of the organ of vision: when the drug gets into the eye - mydriasis, increased intraocular pressure, glaucoma, pain in the eyeball; Sometimes in the treatment of the drug there are reversible disorders of accommodation and glaucoma.

Pain in the eyeball or discomfort, blurred vision, sensation of the appearance of a halo or color spots in front of the eyes, in combination with conjunctival hyperemia and corneal edema may be symptoms of acute glaucoma. You should use the narrowing pupil of the drop and immediately consult an ophthalmologist.

Allergic reactions: rarely - skin rash, angioedema, tongue, lips and face, urticaria.

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

Overdose:

Symptoms Overdoses are usually associated with the action of fenoterol.There may be symptoms associated with excessive stimulation of beta-adrenergic receptors. Most likely the appearance of tachycardia, palpitation, tremor, increased blood pressure, increasing the difference between systolic and diastolic blood pressure, angina pectoris, arrhythmia and the feeling of "tides" of blood to the face, a feeling of heaviness behind the sternum, increased bronchial obstruction, metabolic acidosis. Possible symptoms of overdose caused by ipratropium bromide (such as dry mouth, disruption of accommodation) are weak and transient, which is explained by its local application.

Treatment: recommended the appointment of sedatives, anxiolytic drugs (tranquilizers), in severe cases - intensive therapy.

As a specific antidote, beta-blockers may be used, preferably selective β₁adrenoblockers. However, patients with bronchial asthma or COPD should consider the possibility of strengthening bronchial obstruction, which can lead to death under the influence of beta-blockers and carefully select their dose.

Interaction:

Simultaneous use of other beta-adrenomimetic drugs, anticholinergic drugs of systemic action and xanthine derivatives (for example, theophylline) can enhance the bronchodilating effect of the preparation Ipraterol-native.

Perhaps a significant weakening of the bronchodilator action of the drug with the simultaneous administration of beta-blockers.

Hypokalemia associated with the use of beta-adrenomimetics can be enhanced by the simultaneous administration of xanthine derivatives, glucocorticosteroids and diuretics. This fact should be given special attention in the treatment of patients with severe forms of obstructive airway disease. Hypokalemia can lead to an increased risk of arrhythmias in patients receiving digoxin. In addition, hypoxia can increase the negative effect of hypokalemia on the heart rhythm. In such cases, it is recommended to monitor the potassium level in the blood serum.

Caution should be used to assign β₂-adrenergic agents for patients receiving monoamine oxidase inhibitors and tricyclic antidepressants, since these drugs can enhance the action of beta-adrenergic agents.

Inhalation of funds for general anesthesia of halogenated hydrocarbon anesthetics, for example, halothane, trichlorethylene or enflurane, can enhance the effect of beta-adrenergic agents on the cardiovascular system.

Joint use of the preparation of Ipaterol-native with cromoglycic acid and / or glucocorticosteroids increases the effectiveness of therapy.

Special instructions:

In case of sudden rapid increase in dyspnoea (difficulty breathing) should immediately consult a doctor.

Prolonged use:

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

- in patients with bronchial asthma or severe COPD, one should remember the need to conduct or strengthen anti-inflammatory therapy to control the inflammatory process of the airways and the course of the disease.

Regular use of increasing doses of drugs containing β₂-adrenomimetics, such as the preparation of Ipraterol-native, for the relief of bronchial obstruction can cause uncontrolled deterioration of the course of the disease.In the case of increased bronchial obstruction, an increase in the dose of β₂agonists, including the preparation of Ipraterol-native, more than recommended for a long time is not only not justified, but also dangerous. To prevent a life-threatening deterioration in 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 concomitantly with the preparation of Iprateol-native only under medical supervision.

Patients should be instructed about the proper use of the inhaled solution of the preparation Ipraterol-native. To prevent the solution from entering the eyes, it is recommended that the solution used by the nebulizer be inhaled through the mouthpiece. In the absence of the mouthpiece, a face mask that fits snugly should be used. Especially careful to protect the eyes of patients who are predisposed to the development of glaucoma.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. Causes of dizziness and blurred vision while using the drug may have a negative effect on the above ability.

Form release / dosage:Solution for inhalation, 0.25 mg + 0.5 mg / ml.

Packaging:

For 20 ml of the drug in bottles of dark glass with a polyethylene dropper and a screwed polypropylene lid.

One bottle with instructions for use is placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 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.

Terms of leave from pharmacies:On prescription

Registration number:LP-002166

Date of registration:31.07.2013 / 12.11.2015

Expiration Date:31.07.2018

The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia

Manufacturer: & nbsp

NATIVA, LLC Russia

PHARMSTANDART-FORESTRY, OJSC Russia

Information update date: & nbsp27.11.2017

Illustrated instructions

Instructions

Ipraterol-native (Ipraterol-nativ)