Berodual N, aerosol 20 mcg+50 mcg/dose 200 doses

Contains two components of the combined bronchodilator with bronchodilator activity: ipratropium bromide – m-cholinoblocker, and fenoterol hydrobromide – beta2-adrenomimetic.

In inhaled use of ipratropium bromide bronchodilatation is mainly due to local rather than systemic anticholinergic action. Ipratropium bromide is a quaternary ammonium compound. It has anticholinergic (parasympatholytic) properties.

Ipratropium inhibits reflexes mediated by the vagus nerve by counteracting the effects of acetylcholine, a neurotransmitter released from nerve endings. Anticholinergic agents prevent an increase in intracellular concentration of cyclic guanosine monophosphate (cGMP) in bronchial smooth muscle that occurs during the interaction of acetylcholine with m-cholinoreceptors.

The significant improvement of pulmonary function (increase of BEF1 and mean forced expiratory volume rate by 15% and more) in COPD patients with bronchospasm attacks comes within 15 min, the maximal effect is reached within 1-2 hours and lasts in the majority of patients till 6 hours after the injection. In 40% of patients with bronchospasm associated with bronchial asthma a significant improvement in pulmonary function (increase in SPR1 by 15% or more) is noted.

Ipratropium bromide has no negative effect on airway mucus secretion, mucociliary clearance and gas exchange. Fenoterol hydrobromide has a direct sympathomimetic effect. In therapeutic doses, it selectively stimulates β2-adrenoreceptors of the bronchi. At higher doses, it has the ability to stimulate β1-adrenoreceptors. Binding to β2-adrenoceptors activates adenylate cyclase with participation of stimulating Gs-protein.

Elevated levels of cyclic AMP activate protein kinase A, which then phosphorylates target proteins in smooth muscle cells. This, in turn, leads to phosphorylation of the light chain of myosin kinase, inhibition of phosphoinositide hydrolysis and opening of calcium-activated potassium channels. Fenoterol relaxes smooth muscles of bronchi and vessels and counteracts the development of bronchospastic reactions caused by histamine, methacholine, cold air and allergens (immediate-type hypersensitivity reactions).

Fenoterol blocks the release of bronchoconstrictor mediators of inflammation from mast cells immediately after administration. Use of fenoterol in higher doses increases mucociliary clearance.

Higher plasma concentrations of fenoterol inhibit uterine contractility. In addition, metabolic effects are observed when used in high doses: lipolysis, glycogenolysis, hyperglycemia and hypokalemia. Hypokalemia is mainly due to increased incorporation of potassium ions into skeletal muscle.

The beta-adrenergic effects of the drug on cardiac activity, such as increased HR and heart force, are due to the vascular action of fenoterol, stimulation of β2-adrenoreceptors of the heart, and when used in doses greater than therapeutic, stimulation of β1-adrenoreceptors. As with other beta-adrenergic drugs, prolongation of the QTc interval was observed when used in high doses.

The most frequently observed adverse effect of β2-adrenoreceptor stimulators is tremor. In contrast to the effects on bronchial smooth muscles, tolerance may develop to the systemic effects of β2-adrenoreceptor stimulators. Fenoterol prevents bronchoconstriction caused by various stimuli, such as physical activity, cold air and allergens (immediate-type hypersensitivity reactions).

When ipratropium bromide and fenoterol are used together, the bronchodilator effect is achieved by affecting different pharmacological targets. The mentioned substances complement each other, and as a result the bronchodilator effect increases and provides greater latitude of therapeutic action in bronchopulmonary diseases accompanied with airway constriction.

The complementary action is such that a lower dose of the beta-adrenergic component is required to achieve the desired effect, which facilitates individual dosing of the drug and helps minimize side effects.

Indications

Prevention and treatment of obstructive airway diseases with reversible bronchospasm: Chronic bronchitis complicated or not complicated by emphysema. COPD. Bronchial asthma.

Active ingredient

Composition

1 dose contains:

the active ingredients:

Phenoterol hydrobromide 50 µg;

ipratropium bromide monohydrate 21 µg, which corresponds to the content of ipratropium bromide 20 µg.

excipients:

ethanol absolute,

purified water,

citric acid,

tetrafluoroethane (HFA 134a, propellant).

How to take, the dosage

The dose is set individually, but for relief of bronchial asthma attacks in adults and children over 6 years old 2 inhalation doses are prescribed. If respiratory relief is not achieved within 5 minutes, 2 additional inhalation doses may be prescribed. The patient should be informed that if there is no effect after 4 inhalation doses and additional inhalations are necessary, the patient should immediately consult a physician.

Berodual®H metered dose aerosol in children should only be used as prescribed by a physician and under adult supervision. For prolonged and intermittent therapy, 1-2 inhalations per administration, up to 8 inhalations/day (on average, 1-2 inhalations 3 times/day) are prescribed. The patient should be instructed on the proper use of the metered dose aerosol. Before using a metered dose aerosol the first time, the can should be pressed twice on the bottom of the can. The following rules must be followed each time a metered dose aerosol is used: Remove the protective cap.

Please breathe out slowly and deeply. Hold the balloon with your lips around the mouthpiece. The balloon should be pointing up from the bottom. While taking the deepest breath possible, quickly press down on the bottom of the balloon to release 1 inhalation dose. Hold your breath for a few seconds, then take the mouthpiece out of your mouth and breathe out slowly.

Repeat for the 2nd inhalation dose. Put on the protective cap. If the aerosol can has not been used for more than 3 days, before using it, press once on the bottom of the can until the aerosol cloud appears. Can be used for 200 inhalations. The cylinder should then be replaced. There may still be some content in the can, but the amount of medication released decreases with inhalation.

Interaction

Beta-adrenomimetics and anticholinergic agents, xanthine derivatives (including theophylline) may increase the bronchodilator effect of Berodual H.

Inhaled anesthesia agents containing halogenated hydrocarbons (including halothane, trichloroethylene, enflurane) may increase the cardiovascular effects of Berodual H.

Concomitant use of other beta-adrenomimetics, anticholinergic agents or xanthine derivatives (including theophylline) in the systemic bloodstream may increase the side effects. A significant weakening of the bronchodilator effect of Berodual N in concomitant administration of beta-adrenoblockers is possible.

When used concomitantly with MAO inhibitors and tricyclic antidepressants, increased action of Berodual H is noted. During the use of Berodual H hypokalemia may develop, which may be increased when concomitantly prescribed with xanthine derivatives, GCS and diuretics.

This fact should be considered when treating patients with severe forms of obstructive airway disease. Hypokalemia increases the risk of arrhythmias in patients receiving digoxin. In addition, the negative effect of hypokalemia on cardiac rhythm increases during hypoxia. In such cases, it is recommended to monitor serum potassium levels.

Special Instructions

In patients with a history of cystic fibrosis, GI motility disorders may occur when using Berodual H. Concomitant anti-inflammatory therapy for COPD in patients with effective GCS and bronchial asthma should be considered.

In long-term use in patients with bronchial asthma or mild to moderate forms of COPD, symptomatic treatment may be preferable to regular use. With long-term use in patients with bronchial asthma or steroid-dependent forms of COPD, it should be remembered that anti-inflammatory therapy should be performed or intensified to control airway inflammation and the course of the disease.

The regular use of Berodual H in increasing doses to relieve bronchial obstruction may cause uncontrolled worsening of the disease course. If bronchial obstruction worsens, simply increasing the dose of Berodual H beyond the recommended dose over an extended period of time is not only unwarranted but also dangerous.

In order to prevent a life-threatening worsening of the course of the disease, a review of the patient’s treatment plan and adequate anti-inflammatory therapy with inhaled GCS should be considered. The patient should be informed to see a physician if dyspnea suddenly develops and rapidly progresses.

Other sympathomimetic bronchodilators should be prescribed concomitantly with Berodual H only under medical supervision. The patient should be informed about the rules of inhaler use. Pain in the eye, blurred vision, sensation of a halo or colored spots in front of the eyes combined with redness of the eye as conjunctival or corneal injection may be signs of an acute attack of closed-angle glaucoma.

If the above symptoms occur in any combination, the patient should start treatment with eye drops that cause pupil constriction and seek specialized medical care immediately.

Contraindications

Children under 6 years of age. First trimester of pregnancy. Hypertrophic obstructive cardiomyopathy. Tachyarrhythmia. Hypersensitivity to the components of the drug.

High sensitivity to atropine-like substances.

With caution: Use the drug in closed-angle glaucoma, coronary insufficiency, arterial hypertension, insufficiently controlled diabetes, recently suffered myocardial infarction, severe organic diseases of the cardiovascular system, hyperthyroidism, pheochromocytoma, prostatic hypertrophy, bladder neck obstruction, cystic fibrosis, in children over 6 years.

Side effects

Allergic reactions: rare – skin rash, angioedema of the tongue, lips, face, urticaria, laryngospasm, laryngeal edema, anaphylactic shock.

CNS disorders: often – fine tremor of skeletal muscles, nervousness; sometimes – headache, dizziness, (especially in patients with aggravating factors); in single cases – mental changes.

Cardiovascular system: sometimes – tachycardia, palpitations (especially in patients with risk factors); rarely (when used in high doses) – decrease of diastolic BP, increase of systolic BP, arrhythmia, fibrillation, supraventricular tachycardia.

Water-electrolyte balance: sometimes – pronounced hypokalemia.

Respiratory system: sometimes – cough, local irritation (pharyngitis); rarely – paradoxical bronchospasm.

As for the visual system: rarely – reversible accommodation disorder, mydriasis, increased intraocular pressure, closed-angle glaucoma, pain in the eyeball.

Others: possibly increased sweating, weakness, myalgia, seizures; rarely – reversible urinary retention.

Gastrointestinal system: frequently – dry mouth; sometimes – nausea, vomiting; rarely – reversible disorders of gastrointestinal motility (constipation, diarrhea).

Overdose

Symptoms: fenoterol hydrobromide and caused by overstimulation of β-adrenoreceptors: tachycardia, palpitations, tremors, arterial hypo- or hypertension, increased pulse BP, angina, arrhythmias, flushes and symptoms of ipratropium bromide overdose: dry mouth, impaired accommodation – due to the great breadth of the therapeutic action and inhalation use, are usually little pronounced and are transient in nature.

Treatment:appointment of tranquilizers, sedatives. If necessary – intensive therapy. As a specific antidote, beta-adrenoblockers may be used, preferably selective beta1-adrenoblockers. However, we should remember about possible intensification of bronchial obstruction under the influence of beta-adrenoblockers and carefully select the dose for patients with bronchial asthma or COPD, due to the risk of severe bronchospasm, which may lead to death.

Pregnancy use

It is contraindicated in the first trimester of pregnancy. Current experience has shown that ipratropium bromide and fenoterol hydrobromide have no adverse effects in pregnancy.

However, Berodual®H should be used with caution in the second and third trimesters of pregnancy. The possibility of an inhibitory effect of Berodual H on uterine contractile activity should be considered. Fenoterol hydrobromide is excreted with breast milk. There are no data confirming the excretion of ipratropium bromide with breast milk.

Significant effects of ipratropium on the infant, especially when used as an aerosol, are unlikely. However, given the ability of many medications to penetrate into breast milk.

Berodual®H should be used with caution during lactation (breastfeeding).

Similarities