The instruction for medical use
of Berodual® medicine
the Trade name
the International unlicensed name
Is not present
the Dosage form
Solution for inhalations of 20 ml
of 100 ml of solution contain
active agents: a bromide ipratropiya monohydrate of 26.10 mg (25 mg corresponding an ipratropiya to bromide), Fenoterolum hydrobromide of 50.0 mg,
excipients: a benzalkoniya chloride, dinatrium edetat a dihydrate, sodium chloride, 1 M acid chlorohydrogen, the water purified.
Transparent colourless or almost colourless liquid without visible mechanical inclusions, with almost imperceptible smell.
Drugs for treatment of obstructive respiratory diseases. Inhalation sympathomimetics. Sympathomimetics in a combination with other drugs for treatment of obstructive respiratory diseases. Fenoterolum in a combination with other drugs for treatment of obstructive respiratory diseases
the ATX R03AK03 Code
Pharmacokinetics Therapeutic Effect properties at combination an ipratropiya of bromide and
Fenoterolum of hydrobromide is reached due to local action in airways. The pharmacodynamics of a bronkhodilatation is not connected with
pharmacokinetics of active components of drug.
After inhalation in airways from 10 to 39% of a dose are besieged. A part of the dose which is besieged in lungs quickly reaches a blood-groove (within several minutes), and the amount of the active ingredient remaining in an oral cavity gets inside gradually through a GIT.
Thus, system influence is defined by both oral, and pulmonary bioavailability.
There are no confirmed data on the fact that the pharmacokinetics of two components in a combination differs from pharmacokinetics of each component separately.
the part of drug which Got inside mostly is metabolized with education sulfate of conjugates. Absolute bioavailability – low (about 1.5%). After inhalation about 1% of the inhaled dose it is allocated in the form of free Fenoterolum in urine in 24 hours. The general system bioavailability – 7%. Communication with proteins of blood plasma – 40%. The general clearance of Fenoterolum is 1.8 l/min, and renal clearance –
0.27 l/min. Fenoterolum and its metabolites do not get through a blood-brain barrier. The general excretion with urine in 48 hours –
39% of a dose, through a GIT – 40.2% of a dose.
Cumulative renal excretion a bromide ipratropiya per day – less than 1% of an oral dose of BERODUALA. The general system bioavailability at oral introduction is 2%. Communication with proteins of blood plasma less than 20%.
Terminal elimination half-life – about 1.6 h. The general clearance an ipratropiya – 2.3 l/min, renal clearance – 0.9 l/min. Cumulative renal excretion in 6 days – 9.3%, through a GIT – 88.5%. Elimination half-life makes 3.6 h. Binding of the main metabolites in urine with a muskarinovy receptor is very insignificant.
BERODUAL pharmacodynamics – the combined drug consisting of two bronkhodilatiruyushchy components: an ipratropiya the bromide (having anticholinergic effect) and Fenoterolum hydrobromide (beta2-adrenomimetik).
Ipratropiya bromide is to quarternary derivatives of ammonium and has anticholinergic (parasympatolytic) properties. Ipratropy brakes the reflexes mediated by vagus nerve, counteracting effect of acetylcholine – the neurotransmitter which is released from vagus nerve. Anticholinergics prevent increase in intracellular concentration of Sa ++, arising in interaction of acetylcholine with muskarinovy receptors in smooth muscles of bronchial tubes. Release of Sa ++ mediirutsya by the system of secondary messages consisting of IP3 (inositol triphosphate) and DAG (ditsilglitserol).
Ipratropiya bromide has no negative effect on secretion of slime in airways, mukotsiliarny clearance and gas exchange.
Fenoterolum hydrobromide has direct sympathomimetic effect, selectively stimulating beta2-adrenoceptors in therapeutic doses. At higher doses he is capable to stimulate beta1-adrenoceptors. Linking with beta2-adrenoceptors activates adenylatecyclase with the participation of the stimulating Gs-protein.
The increased level of cyclic AMF activates a protein kinase And which then phosphorylates proteins target in smooth muscle cells. It, in turn, leads to phosphorylation of a light chain of a miozinkinaza, inhibition of hydrolysis of a fosfoinozitid and opening of the potassium channels activated by calcium.
Fenoterolum hydrobromide relaxes smooth muscles of bronchial tubes and vessels and prevents development of the bronkhospastichesky reactions caused by influence of a histamine, metasincaline, cold air and allergens (reactions of immediate hypersensitivity). Right after use Fenoterolum slows down release of bronkhosuzhivayushchy and pro-inflammatory mediators from mast cells. Use of higher doses of Fenoterolum (0.6 mg) increases mukotsiliarny clearance.
At higher concentrations of Fenoterolum in blood plasma which are most often reached at oral administration the contractility of a uterus slows down. Also when using higher doses metabolic effects are observed: a lipolysis, a glycogenolysis, a hyperglycemia and a hypopotassemia which is caused by the increased consumption of ions of K+ skeletal muscles. Beta and adrenergic impacts on heart, such as increase in frequency and force of warm reductions are a consequence of influence of Fenoterolum on vessels, stimulations of beta2-adrenoceptors of a myocardium and, when using the doses exceeding therapeutic, beta1-adrenoceptors. As well as when using other beta and adrenergic drugs the lengthening of an interval of QT when using high dosed
by the Most often observed effect of influence of beta-agonists was noted the tremor is. Unlike impact on smooth muscles of bronchial tubes, system influence of beta-agonists can lead to stability development.
At combined use an ipratropiya of bromide and Fenoterolum the bronkhodilatiruyushchy effect is reached by impact on various pharmacological targets. Two active agents supplement each other, the spasmolytic effect concerning muscles of bronchial tubes as a result amplifies and the big width of therapeutic action in the bronchopulmonary diseases which are followed by narrowing of airways is provided. Complementary action such is that for achievement of desirable effect is required very low dose of a beta and adrenergic component that facilitates individual drug dosing and promotes reduction of undesirable reactions.
At a sharp bronchospasm drug BERODUAL is effective right after introduction and, therefore, is also suitable for treatment of bad attacks of a bronchospasm.
– prevention and symptomatic treatment of obstructive respiratory diseases with a reversible bronchospasm (a chronic obstructive pulmonary disease, bronchial asthma, the chronic obstructive bronchitis complicated or uncomplicated emphysema).
The route of administration and doses
Treatment should be begun with the smallest recommended dose always.
The dose should be selected individually and to regulate according to weight of a bad attack. At sufficient decrease in symptoms the administration of drug should be stopped. The following doses are recommended:
Adults (including elderly people) and teenagers are more senior than 12 years:
Bad attacks of a bronchospasm
Depending on weight of attacks of a dose can vary from 261 mkg
a bromide ipratropiya / 500 hydrobromide Fenoterolum mkg (1 ml of =20 drops) up to 652.5 mkg a bromide ipratropiya / 1250 hydrobromide Fenoterolum mkg (2.5 ml of =50 drops). In exclusive, especially hard cases, use of the doses reaching 1044 mkg a bromide ipratropiya / 2000 hydrobromide Fenoterolum mkg (4 ml of =80 drops) is possible.
IInstruktsiya on use
Solution for inhalations should be used only for inhalations (with the corresponding nebulizer), intake of solution is inside forbidden.
The recommended dose needs to be diluted with normal saline solution up to the final volume which is 3-4 ml and to apply by an inhalation method by means of the nebulizer.
BERODUALA solution for inhalations cannot be dissolved with the distilled water.
Solution needs to be diluted anew every time before
use, residues of divorced solution should be destroyed. Inhalation by divorced solution should be carried out right after preparation.
Duration of inhalation can be controlled by means of dilution volume.
BERODUALA solution can be applied to inhalations with use of various available models of the spraying devices (nebulizers). In the presence of stationary oxygen the optimum rate of administering of solution is 6 – 8 l/min.
Many of the listed undesirable effects can be a consequence of anticholinergic and beta and adrenergic properties of drug BERODUAL.
Side effects decided on the following frequency:
Often (≥ 1/100 – & lt, 1/10), infrequently (≥ 1/1.000 – & lt, 1/100), it is rare (≥ 1/10.000 – & lt, 1/1.000)
– a headache, a tremor, dizziness
– tachycardia, a cardiopalmus
– pharyngitis, a dysphonia,
– vomiting, nausea, dryness in an oral cavity
– increase in systolic arterial blood pressure
– anaphylactic reactions, hypersensitivity
– a hypopotassemia
– disturbing excitement, mental disorders
– glaucoma, increase in intraocular pressure, accommodation disturbance, mydriasis, deterioration in visual acuity, eye pain, cornea hypostasis, conjunctival hyperaemia, Galo (existence in sight of iridescent circles around a light source)
– arrhythmia, including an atrial fibrillation, supraventricular tachycardia, myocardium ischemia
– a bronchospasm, irritation in a throat, throat hypostasis, a laryngospasm, a paradoxical bronchospasm, dryness in a throat, stomatitis, a glossitis, disturbance of motility of digestive tract, diarrhea, a constipation, mouth hypostasis
– urticaria, rash, an itching, a Quincke’s edema, a hyperhidrosis
– muscle weakness, muscular spasms, myalgia, an urination delay, lowering of diastolic arterial blood pressure.
– hypersensitivity to Fenoterolum to hydrobromide, atropinopodobny substances or other components of drug
– a hypertrophic subaortic stenosis
– a tachyarrhythmia
– pregnancy (I trimester)
– children up to 12 years
Systematic combined use of BERODUAL medicine with other anticholinergics was not studied, in this regard their combined use is not recommended.
Beta and adrenergic and anticholinergics, ksantinovy derivatives (for example, theophylline) can strengthen bronkhodilatiruyushchy effect of drug BERODUAL. Co-administration of other beta-adrenergic agonists getting to a system blood stream of anticholinergics or ksantinovy derivatives (for example, theophylline) can lead to strengthening of side effects.
Perhaps considerable weakening of bronkhodilatiruyushchy action of BERODUAL at co-administration of beta blockers.
The hypopotassemia connected with intake of agonists of beta2-adrenoceptors can be strengthened by co-administration of ksantinovy derivatives, glucocorticosteroids and diuretics. It should pay special attention at treatment of patients with severe forms of obstructive respiratory diseases.
The hypopotassemia can lead to increase in risk of developing of arrhythmias at the patients receiving digoxin. Besides, the hypoxia can increase negative impact of a hypopotassemia on a warm rhythm. In similar cases it is recommended to carry out control of potassium concentration in blood serum.
With care it is recommended to appoint the medicines containing agonists of beta2-adrenomimetik, to the patients receiving inhibitors of a monoaminooxidase and tricyclic antidepressants as these drugs are capable to strengthen action of beta2-adrenoceptors.
Inhalations of the halogenated hydrocarbon anesthetics, for example a halothane, trichloroethylene or an enfluran, can strengthen adverse influence of beta and adrenergic funds for a cardiovascular system.
indications Hypersensitivity Later of administration of drug BERODUAL can develop immediate hypersensitivity reactions what point exceptional cases of an urticaria, Quincke’s disease, rash, a bronchospasm, hypostasis of oropharyngeal area and anaphylaxis to.
A paradoxical bronchospasm
It is similar to other drugs for inhalations, use of BERODUALA can lead to a paradoxical bronchospasm, life-threatening. At emergence of a paradoxical bronchospasm the use of BERODUALA should be stopped and replaced immediately it with alternative treatment.
of BERODUAL should be used with care at the patients predisposed to closed-angle glaucoma.
Separate reports on ophthalmologic complications such as were submitted: a mydriasis, the increased intraocular pressure, closed-angle glaucoma, pain at hit in eyes inhalation a bromide ipratropiya (or a bromide ipratropiya in combination with agonists of beta2-adrenoceptors).
Patsiyentov it is necessary to instruct in detail concerning rules of use of the dosed aerosol inhaler of BERODUAL and to warn about measures for protection of eyes!
Pain and discomfort in eyes, the obscured sight, existence in sight of iridescent circles around a light source or reddening of eyes owing to conjunctival hyperaemia and hypostasis of a cornea can be symptoms of closed-angle glaucoma. At development of any combination of these symptoms it is necessary to begin treatment with miotic drops and to consult immediately with the doctor.
of BERODUAL should be used only after careful assessment of risk/advantage, especially in case of use of high doses, in the following situations: insufficiently controlled diabetes, recently postponed myocardial infarction, crushing organic lesions of heart and vessels, a hyperthyroidism, a pheochromocytoma or the accompanying obstruction of urinary tract (for example, a hyperplasia of a prostate or obstruction of a neck of a bladder).
Influence on cardiovascular activity
Sympathomimetic means, including BERODUAL, can influence a cardiovascular system. There are data confirming exceptional cases of development of the ischemia of a myocardium connected with reception of beta-agonists. The patients with the basic serious illness of heart (e.g. coronary heart disease, arrhythmia or heavy heart failure) accepting BERODUAL have to be warned about need of the request for medical care in case of appearance of the stethalgias or other symptoms of aggravation of symptoms connected with a heart disease. It is necessary to pay attention to assessment of such symptoms as short wind and a stethalgia as they can be either respiratory, or warm origin.
Potentially serious hypopotassemia can be a consequence of therapy by agonists of beta2-adrenoretstor.
Disturbances of motility of digestive tract
Patients with cystous fibrosis can be more inclined to disturbances of motility of digestive tract.
in case of the sharp, quickly aggravated asthma, to patients is recommended to consult immediately with the doctor.
– patients with bronchial asthma should use BERODUAL only as required. To patients with the HOBL easy forms the treatment on demand (depending on existence of symptoms) can be more preferable than regular use
– addition or strengthening of anti-inflammatory therapy for control of inflammation of upper airways and prevention of deterioration in a disease is reasonable concerning patients with bronchial asthma and a glucocorticosteroid – dependent HOBL.
Regular use of the increasing doses of the drugs containing beta2-agonists such as BERODUAL, for control of symptoms of bronchial obstruction can cause deterioration in a course of the disease. In case of strengthening of bronchial obstruction the simple increase in a dose of beta2-agonists, in particular BERODUALA recommended above for a long time not only is not reasonable, but also it is dangerous. For prevention of life-threatening deterioration in a course of the disease in this situation it is necessary to consider a question of revision of the treatment plan of the patient and adequate anti-inflammatory therapy by inhalation corticosteroids.
It is necessary to appoint other sympathomimetic bronchodilators along with drug BERODUAL only under medical observation.
Prevention concerning doping
can result Use of drug BERODUAL in positive takes of tests concerning Fenoterolum for abuse of psychoactive substances on not medical indications, for example for increase in sporting achievements (doping).
The fertility, pregnancy and the period of a lactation
Data of preclinical trials and experience of use for the person demonstrate that Fenoterolum or ipratropiya does not cause development of side reaction at pregnancy. Nevertheless, it is necessary to observe the usual precautionary measures connected with use of medicines during pregnancy, especially in the first trimester.
It is necessary to consider a possibility of the inhibiting influence of BERODUAL on sokratitelny activity of a uterus.
Fenoterolum lactation period hydrobromide can get into breast milk, in the relation a bromide ipratropiya such data are not obtained. Significant influence an ipratropiya on the baby, especially in case of use of drug in the form of aerosol, is improbable. Nevertheless, the feeding women should appoint drug BERODUAL with care.
Clinical data on influence on fertility at the combined use an ipratropiya of bromide and Fenoterolum of hydrobromide and also each of two components, no. However data of preclinical trials were shown by lack of negative influence on fertility of the person of Fenoterolum of hydrobromide and a bromide ipratropiya separately.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
of Researches of influence of drug on ability to run motor transport and to work with mechanisms it was not carried out.
Nevertheless, it is necessary to inform patients on such possible side reactions as dizziness, a tremor, accommodation disturbance, mydriasis and deterioration in visual acuity during reception of BERODUALA. It is recommended to be careful during the driving or work with mechanisms. In case of emergence in patients of the above-stated side effects, it is necessary to avoid performance of such operations, potentially dangerous to them, as driving or work demanding exact coordination of movements and speed of psychomotor reactions.
Symptoms: symptoms of overdose are usually connected mainly with effect of Fenoterolum.
Emergence of the symptoms at overdose connected with excess stimulation of beta adrenoceptors is possible. Appearance of tachycardia, heartbeat, a tremor, arterial hypertension or arterial hypotension, increase in pulse pressure, pains as a result of stenocardia, arrhythmias and inflows is the most probable.
The metabolic acidosis and a hypopotassemia can be observed at use of Fenoterolum in higher doses, than it is recommended.
Possible symptoms of overdose a bromide ipratropiya (dryness in a mouth, disturbance of accommodation of eyes), are expressed poorly that the ipratropiya is explained by very low system availability inhalation.
Treatment: the BERODUAL drug treatment should be stopped. It is necessary to carry out acid-base and electrolytic monitoring. Use of sedativnykhsredstvo, tranquilizers, in hard cases – intensive care is recommended.
As specific antidote the use of beta blockers, preferably beta1-selection adrenoblockers is possible. However it is necessary to remember possible strengthening of bronchial obstruction under the influence of beta blockers and to carefully select a dose for the patients having bronchial asthma or HOBL in connection with danger of development of a heavy bronchospasm which can lead to a lethal outcome.
The form of release and packing
On 20 ml of drug spill in the bottles of dark glass corked by a stopper dropper and the screwing-up cover.
On 1 bottle together with the instruction for medical use in the state and Russian languages put in a pack cardboard.
To Store storage conditions at a temperature not above 30 °C. Not to freeze!
To store out of children’s reach!
not to use a period of storage after the expiry date specified on packing.
According to the prescription of the doctor
of Proizvoditel Institut de Angueli S.R. L., Italy
the Owner of the registration certificate
of Boehringer Ingelcheim International GmbH, Germany
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) Representation “Boehringer Ingelcheim of Pharm Hess mbkh” in RKAdres: Almaty, 050008, the ave of Abay, 52 Business center “Innova Tower”, the 7th was etazhtet + 7 (727) 250 00 77, fax: +7 (727) 244 51 77 by e-mail-mail