Ipratropium bromide + Fenoterol - instructions for use, dose, side effects, contraindications

Combined drug with a pronounced bronchodilator effect due to the action of the constituent fenoterol and ipratropium bromide. Fenoterol has a bronchodilator effect, selectively stimulating beta₂-adrenoreceptors of bronchi. Ipratropium bromide eliminates m-holinostimulating effects on the smooth muscles of the bronchi and reduces the production of sputum due to blockade M₃cholinergic receptors of the bronchi, does not adversely affect mucociliary clearance and gas exchange.

In the joint application of ipratropium bromide and fenoterol bronchodilator effect is achieved by affecting various pharmacological targets. These substances complement each other,As a result, the spasmolytic effect on bronchial muscles increases and a greater breadth of therapeutic effect is achieved with bronchopulmonary diseases accompanied by constriction of the respiratory tract. Complementary action is such that, in order to achieve the desired effect, a lower dose of the beta-adrenergic component is required, which allows individual selection of an effective dose in the practical absence of side effects.

After inhalation of the drug therapeutic effect is observed after 15 minutes, reaches a maximum after 1-2 hours and lasts up to 6 hours.

Pharmacokinetics:

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. Do not cumulate. Ipratropium bromide is excreted mainly through the intestine. About 25% is excreted unchanged, the rest - in the form of numerous metabolites.

Fenoterol

When inhaled fenoterola effect occurs after 5 minutes, the maximum severity of the effect is observed within 0.5-1.5 hours after inhalation, the duration of the action is 3-6 hours.

When administered orally, the effect occurs after 30-60 minutes, the maximum severity of the effect is observed within 2-3 hours after administration, the duration of action is 6-8 hours.

After oral administration fenoterol completely absorbed from the digestive tract. Bioavailability of 60%. Relationship with plasma proteins 40-55%. Biotransformation in the liver to pharmacologically inactive sulfates. Intensively metabolized when the "first pass" through the liver. It is excreted in bile and urine almost completely in the form of inactive sulfate conjugates.

After inhalation, low concentrations are created in the blood.

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.

ICD-10

I.A15-A19 Tuberculosis

X.J40-J47.J43 Emphysema

X.J40-J47.J44 Other chronic obstructive pulmonary disease

X.J40-J47.J45 Asthma

X.J40-J47.J46 Asthmatic status [status asthmaticus]

Contraindications:Hypersensitivity(including atropine and its compounds), tachyarrhythmia, hypertrophicI obstructive cardiomyopathy, pregnancy (I and III term), children's age (up to 6 years).

Carefully:Coronary insufficiency, arterial hypertension, diabetes mellitus (insufficiently controlled), recently transferred myocardial infarction (during the last 3 months), severe organic diseases of the heart and blood vessels (heart failure, ischemic heart disease, heart disease, aortic stenosis, severe cerebral and peripheral arterial lesions), hyperthyroidism, pheochromocytoma, prostatic hyperplasia, bladder neck obstruction, angle-closure glaucoma, cystic fibrosis, childhood, II trimester of pregnancy, the period of breastfeeding.

Pregnancy and lactation:

FDA recommendation category D. The drug is contraindicated in the I and III trimesters (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, care should be taken to prescribe the drug to nursing mothers.

Dosing and Administration:

Inhalation. Aerosol for inhalation: adults and children over 6 years - usually 1-2 doses of aerosol 3 times a day. If there is a threat of development of respiratory failure - 2 doses of aerosol, if necessary - after 5 minutes 2 more doses, the subsequent inhalations are carried out not earlier than in 2 hours.

Solution for inhalation: adults and children over 12 years for relief of seizures - 1 ml (20 drops) of the solution, in severe cases, the dose can be increased to 2.5-4 ml (50-80 drops). Long intermittent therapy - 1-2 ml (20-40 drops) up to 4 times a day. In the case of moderate bronchospasm or the need for ancillary (artificial) ventilation, lower doses are recommended - 0.5 ml (10 drops).

Children 6-12 years: seizures - 0.5-1 ml (10-20 drops), in severe cases, the dose can be increased to 3 ml (60 drops). Prolonged and intermittent therapy: 0.5-1 ml (10-20 drops) up to 4 times a day. In the case of moderate bronchospasm or the need for auxiliary (artificial) ventilation, lower doses are recommended - 0.5 ml (10 drops).

Children under 6 years old (body weight up to 22 kg): the dose is determined from the calculation of 25 μg ipratropium bromide and 50 μg fenoterol per 1 kg body weight, respectively to 0.5 ml (10 drops) 3 times a day.

The recommended dose of the drug is diluted immediately before use in 0.9% NaCl solution (not diluted in distilled water!) To a total volume of 3-4 ml and inhaled through a nebulizer for 6-7 minutes until the solution is consumed completely. The dose may depend on the inhalation regimen and the technical characteristics of the nebulizer. The duration of inhalation can be controlled through the volume of the diluted solution. If necessary multiple inhalations, the interval between them should be at least 4 hours.

Side effects:

The most common side effects reported in clinical studies were cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, increase in systolic blood pressure and nervousness.

From the immune system: anaphylactic reaction, hypersensitivity.

From the side of metabolism: hypokalemia.

From the nervous system and psyche: nervousness, agitation, mental disorders, headache, tremor, dizziness.

From the side of the organ of vision: glaucoma, increased intraocular pressure, accommodation disorders, mydriasis, blurred vision, eye pain, corneal edema, conjunctival hyperemia, the appearance of an aura around objects.

From the cardiovascular system: tachycardia, palpitations, arrhythmias, atrial fibrillation, supraventricular tachycardia, myocardial ischemia, increased systolic blood pressure, increased diastolic blood pressure.

From the respiratory system: cough, pharyngitis, dysphonia, bronchospasm, throat irritation, pharyngeal edema, laryngospasm, paradoxical bronchospasm, dry pharynx.

From the digestive system: vomiting, nausea, dry mouth, stomatitis, glossitis, gastrointestinal motility disorders, diarrhea, constipation, edema of the oral cavity.

From the skin and subcutaneous tissues: urticaria, itching, angioedema, hyperhidrosis.

From the musculoskeletal system: muscle weakness, spasm of muscles, myalgia.

From the urinary system: retention of urine.

Overdose:

Symptoms: symptoms of an overdose are usually associated predominantly with the action of fenoterol (the appearance of symptoms associated with excessive stimulation of beta-adrenergic receptors). The most likely occurrence of tachycardia, palpitations, tremors, increased or decreased blood pressure, increased differences between systolic and diastolic blood pressure, angina pectoris, arrhythmias, feelings of blood flush to the face, a sense of heaviness behind the sternum, increased bronchial obstruction, metabolic acidosis.

Possible symptoms of overdose caused by the action of ipratropium bromide (such as dry mouth, violation of eye accommodation) are weak and transient, which is explained by the wide therapeutic range of doses of this drug and its local application.

Treatment: recommended the use of sedatives, tranquilizers; in severe cases - intensive therapy.

As a specific antidote, the use of beta-adrenergic receptor blockers is possible, preferably selective beta₁adrenoblockers. However, in patients with bronchial asthma or chronic obstructive pulmonary disease,take into account the possibility of strengthening bronchial obstruction under the influence of beta-blockers and carefully select their dose.

Interaction:

Simultaneous use with xanthine derivatives, other beta-adrenomimetic agents, cromoglycic acid and glucocorticosteroids enhances bronchodilator effect, with beta-adrenoblockers - weakens.

Xanthine derivatives, glucocorticosteroids and diuretics increase hypokalemia. Halogen-containing hydrocarbon medicines for general anesthesia (halothane, trichlorethylene, enflurane) increase the risk of cardiovascular side effects.

MAO inhibitors, tricyclic antidepressants increase beta-adrenostimulating effect.

Special instructions:

The patient should be informed that in case of sudden rapid increase of dyspnea (difficulty breathing), immediately consult a doctor.

Shortly before birth, the reception should be discontinued due to the possibility of weakening the birth activity of fenoterol.

Avoid contact with the eye. Patients with a history of cystic fibrosis may have GI motility disorders.

A solution for inhalation can be used with a variety of inhalation devices. If there is a centralized stationary supply of oxygen, it is better to inject the solution at a rate of 6-8 liters per minute.

In athletes, the use of the drug in connection with the presence of phenoterol in its composition can lead to positive results of doping tests.

The drug contains a preservative - benzalkonium chloride and a stabilizer-disodium edetate dihydrate. During inhalation, these components can cause bronchospasm in sensitive patients with airways hyperreactivity.

Impact on the ability to drive vehicles and manage mechanisms

Studies of the effects of the drug on the ability to drive vehicles and the use of mechanisms were not carried out. However, patients may experience such undesirable sensations as dizziness, tremors, disorders of eye accommodation, mydriasis and blurred vision. Therefore, care should be taken when driving vehicles or using mechanisms.

Instructions

Ipratropium bromide + Fenoterol (Ipratropii bromidum + Phenoterolum)