Berodual N (Aerosol inhalation)

Active material: Fenoterol, Ipratropiya bromide
When ATH: R03AK03
CCF: Bronchodilators
ICD-10 codes (testimony): J43, J44, J45
When CSF: 12.01.05
Manufacturer: BOEHRINGER INGELHEIM PHARMA GmbH & Co. KG (Germany)

DOSAGE FORM, COMPOSITION AND PACKAGING

Aerosol for inhalation dose in the form of a transparent, colorless or slightly yellowish, or slightly brownish liquid, free from suspended particles.

1 dose
Fenoterol gidrobromid50 g
ïpratropïya bromide monohydrate21 g,
which corresponds to the content of ipratropium bromide20 g

Excipients: Ethanol absolute, Purified water, lemon acid, tetrafluoroethane (HFA 134a, propellant).

10 ml (200 doses) – metal cans with a metering valve and mouthpiece (1) – packs cardboard.

 

Pharmacological action

Combined bronchodilators. It contains two components, having bronchodilator activity: ipratropiya bromide – Mr. holinoblokator, and fenoterol hydrobromide – beta2-adrenomimetik.

When inhaled ipratropium bromide application bronchodilation caused, mainly, local, instead systemic anticholinergic.

Ipratropium bromide is a quaternary ammonium compound. It has anticholinergic (parasympatholytics) properties. Ipratropium inhibits reflexes, mediated by the vagus nerve, counteracting the effect of acetylcholine - a neurotransmitter, released from the nerve endings. Anticholinergics prevent the increase in the intracellular concentration of cyclic guanosine monophosphate (cGMP) in the smooth muscles of the bronchi, arising from the interaction of acetylcholine with the m-cholinergic receptors.

Significant improvement of lung function (increase in FEV1 and mean forced expiratory volume velocity on 15% and more) COPD patients with bouts of bronchospasm occurs within 15 m, maximum effect is achieved after 1-2 h and continuing until the majority of patients 6 hours after injection.

In 40% patients with bronchospasm, associated with asthma, It showed a significant improvement in lung function (increase in FEV1 on 15 % and more).

Ipratropium bromide has no adverse effect on mucus secretion in the airways, mucociliary clearance and gas exchange.

Fenoterol hydrobromide has a direct effect of sympathomimetic. At therapeutic doses, it selectively stimulates β2-adrenergic receptors of the bronchi. At higher doses, it has the ability to stimulate β1-adrenoreceptory. Binding to β2-adrenergic receptors activates adenylate cyclase stimulating the participation Gs-squirrel. Elevated levels of cyclic AMP activates protein kinase A, which then phosphorylates target proteins in smooth muscle cells. It, in turn, It leads to phosphorylation of the light chain miozinkinazy, inhibition of phosphoinositide hydrolysis and the opening of calcium-activated potassium channels.

Fenoterol relaxes bronchial smooth muscle and blood vessels and prevents the development of bronchospastic reactions, due to the influence of histamine, metaxolina, cold air and allergens (immediate hypersensitivity reactions). Immediately after administration of bronchoconstrictor fenoterol blocks the release of inflammatory mediators from mast cells. Application fenoterola higher doses increases mucociliary clearance.

At higher concentrations in plasma fenoterol inhibited uterine contractility. Besides, when used in high doses observed metabolic effects: lipolysis, Glycogenolysis, hyperglycemia and hypokalemia. Hypokalemia is caused, mainly, increased inclusion of potassium ions in skeletal muscle.

Beta-adrenergic effect of the drug on cardiac function, such as increased heart rate and force of heart contractions, due to the action of vascular fenoterol, стимуляцией b2-adrenoreceptors of the heart, and when used in doses, exceeding therapeutic, стимуляцией b1-adrenoreceptorov. As with other beta-adrenergic agents, marked QT prolongationfrom when used in high doses.

The most frequently observed undesirable effect of stimulants β2-adrenoceptor is tremor. In contrast to the effects on bronchial smooth muscle stimulators for systemic effects β2-adrenergic receptors may develop tolerance.

Fenoterol prevents the development of bronchoconstriction, induced by various stimuli, such as exercise, cold air and allergens (immediate hypersensitivity reactions).

When combined ipratropium bromide and fenoterol bronchodilation effect is achieved by acting on different pharmacological targets. These substances are complementary, resulting in enhanced bronchodilator effect and provides a great breadth of therapeutic action in bronchopulmonary diseases, accompanied by constriction of the respiratory tract. Complementary actions such, that to achieve the desired effect requires a lower dose of beta-adrenergic component, facilitating individual dosage adjustment helps to minimize side effects.

 

Pharmacokinetics

Data on the pharmacokinetics of the drug Flomax®H is not provided.

 

INDICATIONS

Prevention and symptomatic treatment of obstructive airways diseases with a reversible bronchospasm:

- COPD;

- Bronchial asthma;

- Chronic bronchitis, complicated or not complicated by emphysema.

 

DOSAGE

Dose set individually.

To acute asthma adults and children over 6 years appointed 2 inhaled dose. If during the 5 min does not come easier breathing, You can assign more 2 inhaled dose.

The patient should be informed, in case of lack of effect after 4 inhaled doses and the need for additional inhalations, should seek medical advice immediately.

Metered aerosol Flomax®H in children should be used only on prescription and under the supervision of adults.

To prolonged and intermittent therapy appointed 1-2 on inhalation 1 reception, to 8 inhalations / day (average, 1-2 inhalation 3 times / day).

Terms of use of the drug

The patient should be instructed on the proper use of metered aerosol.

Before using metered aerosol for the first time by double-click on the valve.

Every time you use a metered aerosol should do the following:

1. Remove the protective cap.

2. Make slow, deep breath.

3. Hold the bottle, clasp lips mouthpiece. The container should be sent upside down.

4. Making the most deep breath, both quickly push the bottom of the bottle before release 1 dose inhalation. For a few seconds, hold your breath, then remove the mouthpiece from the mouth and breathe out slowly. Repeat steps for the 2nd dose inhalation.

5. Wear protective cap.

6. If an aerosol can is not used more than 3 days, Prior to use, single click on the bottom of the container until the aerosol cloud.

The cylinder is designed for 200 inhalations. Then, the cylinder must be replaced. Despite, that the cylinder can be some content, the amount of drug, released during inhalation, decreases.

Because the balloon is opaque, the amount of drug in the cylinder can be determined as follows: removing the protective cap, cylinder is immersed into a container, filled with water. The amount of drug is determined depending on the position of the balloon in water.

The mouthpiece should be kept clean, If necessary, it can be washed in warm water. After using soap or detergent mouthpiece should be thoroughly washed with water.

Plastic mouthpiece developed specifically for metered aerosol Flomax®N and serves for precise dosing of the drug. Mouthpiece should not be used with other dosage aerosols. You can not use metered aerosol Flomax®H with other mouthpieces.

 

SIDE EFFECT

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

Cardio-vascular system: sometimes – tachycardia, palpitations (especially in patients with risk factors); rarely (when used in high doses) – decrease in diastolic blood pressure, increase in systolic blood pressure, arrhythmia, fibrillation, supraventricular tachycardia.

From the water-electrolyte balance: sometimes – severe hypokalemia.

Co respiratory system: sometimes – cough, Local irritation (pharyngitis); rarely - paradoxical bronchospasm.

From the digestive system: often – dry mouth; sometimes – nausea, vomiting; rarely – reversible gastrointestinal dysmotility (constipation, diarrhea).

On the part of the organ of vision: rarely – reversible ccomodation, midriaz, increased intraocular pressure, zakrыtougolynaya glaucoma, pain in the eyeball.

Allergic reactions: rarely – skin rash, angioedema language, lips, person, hives, laringospazm, laryngeal edema, anaphylactic shock.

Other: possible increased sweating, weakness, myalgia, convulsions; rarely – reversible urinary retention.

 

CONTRAINDICATIONS

- Gipertroficheskaya obstruktivnaya cardiomyopathy;

- Dryness;

- I trimester of pregnancy;

- Children up to age 6 years;

- Hypersensitivity to the drug;

- Hypersensitivity to atropine substances.

FROM caution use in patients with angle-closure glaucoma, coronary insufficiency, hypertension, inadequately controlled diabetes, recent myocardial infarction, heavy organic diseases of the cardiovascular system, gipertireoze, pheochromocytoma, prostatic hypertrophy, bladder outlet obstruction, in cystic fibrosis, in children older 6 years.

 

Pregnancy and lactation

The drug is contraindicated for use in the I trimester of pregnancy.

The existing experience shows, that ipratropium bromide and fenoterol hydrobromide not adversely affect pregnancy. Nonetheless, во II и III триместрах беременности Беродуала®H should be used with caution. It is necessary to consider the possibility of inhibiting the action Berodual®H on the contractile activity of the uterus.

Fenoterol hydrobromide is excreted in breast milk. Data, confirming the release of ipratropium bromide in breast milk, not received. Significant impact on infant ipratropium, especially in the case of the drug as an aerosol, unlikely. Nonetheless, Given the ability of many drugs penetrate the breast milk, It should be used with caution Flomax®H lactation (breast-feeding).

 

Cautions

With prolonged use in patients, bronchial asthma or mild and moderate COPD symptomatic treatment may be preferable to regular use.

With long-term use in patients with asthma, or steroid-dependent COPD should be mindful of the need for strengthening or anti-inflammatory therapy to control inflammation of the airways and the disease.

Regular use Berodual®N in increasing doses for relief of bronchial obstruction can cause an uncontrolled deterioration of the disease. In the case of amplification of bronchial obstruction simply increasing the dose Berodual®N longer recommended for a long time not only justified, but also dangerous. To prevent life-threatening deterioration of disease should consider reviewing the patient's treatment plan and an adequate anti-inflammatory therapy with inhaled corticosteroids.

The patient should be informed, that in case of sudden onset and rapid progression of dyspnea, seek medical advice.

Other sympathomimetic bronchodilators should be administered simultaneously with Berodual®H only under medical supervision.

The patient should be informed about the use of the inhaler.

Pain in the eye, blurred vision, feeling of ghosting or color spots before his eyes in combination with red eyes in the form of corneal or conjunctival injection may be signs of an acute attack of angle-closure glaucoma. When these symptoms with any combination of the patient should start the treatment with eye drops, causing constriction of the pupil, and immediately seek specialized medical care.

Patients with a history of instructions for cystic fibrosis may be gastrointestinal dysmotility in the application Berodual®N.

It is considered the feasibility of concomitant anti-inflammatory therapy in COPD patients, whose effective GCS, and in asthma.

 

OVERDOSE

Symptoms associated primarily with the effect of fenoterol hydrobromide and due to excessive stimulation of β-adrenergic receptors: tachycardia, palpitations, tremor, arterïalnaya hypo- or hypertension, an increase in pulse pressure, angina, arrhythmia, tides.

Overdose symptoms ipratropium bromide: dry mouth, ccomodation – in connection with a large therapeutic breadth and the inhalation action using, usually, and have expressed little transitory nature.

Treatment: appointment of sedatives, trankvilizatorov. If necessary, – intensive therapy. As a specific antidote is possible to use beta-blockers, preferably selective beta1-adrenoblokatorov. However, be aware of the possible strengthening of bronchial obstruction under the influence of beta-blockers and carefully select a dose for patients, bronchial asthma or COPD, due to the risk of severe bronchospasm, which can lead to death.

 

Drug Interactions

Beta-agonists and anticholinergics, xanthine derivatives (incl. theophylline) can enhance the effect of bronchodilator Berodual®N.

With simultaneous use of other beta-agonists, entering the systemic circulation anticholinergics or xanthine derivatives (incl. teofillina) may increase the side effects.

Perhaps the significant weakening of bronchodilator action Berodual®N, while the appointment of beta-blockers.

At simultaneous application with MAO inhibitors and tricyclic antidepressants marked potentiation of Berodual®N.

Against the background of Berodual®H may develop hypokalemia, which may be increased with concomitant administration with xanthine derivatives, SCS and diuretics. This fact should be taken into account when treating patients with severe obstructive airway diseases.

Hypokalemia increases the risk of arrhythmias in patients, receiving digoxin. Besides, during hypoxia amplifies the negative impact of hypokalemia on cardiac rhythm. In such cases it is advisable to monitor the level of potassium in blood serum.

Means for inhalation anesthesia, containing halogenated hydrocarbons (incl. halothane, trichlorethylene, enfluran), may enhance the action Berodual®H cardiovascular system.

 

Conditions of supply of pharmacies

The drug is released under the prescription.

 

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.

The cylinder is under pressure. The container can not be opened and exposed to heat above 50 ° C.