Instructions Berotec H metered aerosol 100 mcg/dose metal can 10 ml 200 doses
Composition
active ingredient: fenoterol (1-(3,5-dihydroxy-phenyl)-2-[[1-(4-hydroxy-benzyl)-ethyl]-amino]-ethanol hydrobromide);
1 dose contains fenoterol hydrobromide 100 mcg;
excipients: propellant: 1,1,1,2-tetrafluoroethane (HFA 134a), anhydrous citric acid, purified water, anhydrous ethanol.
Dosage form
Metered aerosol.
Main physicochemical properties: transparent, colorless, slightly yellowish or slightly brownish liquid, free from suspended particles.
Pharmacotherapeutic group
Drugs used in obstructive airway diseases. Selective beta-2-adrenergic agonists.
ATX code R03A C04.
Pharmacological properties
Pharmacodynamics.
Berotec N is an effective bronchodilator for use in acute asthma attacks and other conditions with reversible airway narrowing, such as obstructive bronchitis with or without emphysema. After oral administration, Berotec N begins to act within a few minutes and lasts up to 8 hours.
After inhalation of fenoterol hydrobromide in obstructive pulmonary diseases, bronchodilation occurs within a few minutes. The bronchodilator effect lasts for 3-5 hours.
When used in higher doses, the drug stimulates beta-1-adrenergic receptors (for example, when taken for tocolysis).
Fenoterol relaxes the smooth muscles of the bronchi and blood vessels. The effect of relaxing smooth muscles is dose-dependent. It is believed that it is enhanced by the effect on the adenylate cyclase system in such a way that the binding of beta-agonists to their receptors (stimulated by guanosine binding protein) leads to the activation of adenylate cyclase. As a result of phosphorylation of the protein (protein kinase A), the intracellular content of cAMP increases, which leads to relaxation of smooth muscles. In high doses, fenoterol also affects striated muscles (tremor). In addition, fenoterol inhibits the release of mediators from mast cells. After taking fenoterol at a dose of 0.6 mg, an improvement in mucociliary clearance was noted.
Fenoterol has a positive inotropic and chronotropic (direct and/or reflex) effect on the heart. At high doses, the following metabolic effects are observed: lipolysis, glycogenolysis, hyperglycemia and hypokalemia; the latter is caused by increased K+ absorption, primarily by skeletal muscle. As with other beta-adrenergic agents, prolongation of the QTc interval has been reported. For metered dose inhalers with fenoterol, these were isolated events at doses higher than recommended. The clinical significance has not been established.
Due to the high concentration of beta-2 receptors in the myometrium, fenoterol can relax the muscles of the uterus. This effect is often observed in pregnancy. The tocolytic dose of fenoterol is much higher than the bronchospasmolytic. Therefore, there is a high risk of side effects.
Pharmacokinetics.
The pharmacokinetics of fenoterol have been studied after intravenous, inhalation and oral administration. The therapeutic effect of Berotec N is achieved by local action on the respiratory tract. Thus, the concentration of the drug in the blood plasma does not necessarily correlate with the bronchodilator effect.
After inhalation, depending on the method of inhalation and the system used, about 10-30% of the active substance released from the aerosol reaches the lower respiratory tract. The rest is deposited in the upper respiratory tract and oral cavity and is then swallowed. The absolute bioavailability of fenoterol from the metered dose aerosol BEROTEK N after inhalation is 18.7%.
Absorption after inhalation occurs in a biphasic manner and accounts for 13% of the dose. 30% of the dose of fenoterol hydrobromide is rapidly absorbed with a half-life of 11 minutes, and 70% is slowly absorbed with a half-life of 120 minutes.
After oral administration, approximately 60% of the dose of fenoterol hydrobromide is absorbed. The amount absorbed undergoes extensive one-step metabolism, resulting in a bioavailability of approximately 1.5% when administered orally. Thus, the contribution of the dose of active ingredient ingested by the patient to the plasma concentration after inhalation is negligible. Maximum plasma concentration is reached after approximately 60-120 minutes.
Fenoterol is widely distributed throughout the body. The volume of distribution at steady state after intravenous administration (Vss) is 1.9-2.7 l/kg. The distribution of fenoterol in plasma after intravenous administration is adequately described by a three-compartment pharmacokinetic model with half-lives tα = 0.42 minutes, tβ = 14.3 minutes and tγ = 3.2 hours. Plasma protein binding is from 40 to 55%.
After intravenous administration, the main part (about 85%) of the average total clearance of 1.1-1.8 l/min is provided by biotransformation, including bile excretion. Renal clearance of fenoterol (0.27 l/min) corresponds to approximately 15% of the average total clearance of the systemically available dose. Taking into account the proportion of the drug bound to plasma proteins, the value of renal clearance allows, in addition to glomerular filtration, to assume tubular secretion of fenoterol.
Within 48 hours after oral and intravenous administration, the total radioactivity excreted in the urine is approximately 39% and 65% of the dose, respectively, and the total radioactivity excreted in the faeces is 40.2% and 14.8% of the dose. After oral administration, 0.38% of the dose is excreted in the urine as parent compound, while after intravenous administration, 15% of the compound is excreted unchanged. After inhalation from a metered dose inhaler, 2% of the dose is excreted unchanged by the kidneys within 24 hours.
Unmetabolized fenoterol can cross the placental barrier. Sympathomimetic effects may be observed in the fetus. After long-term infusion, fenoterol levels in the fetal blood were observed that were up to 50% of the maternal concentration. Fenoterol is excreted much more slowly in premature infants than in adults.
Fenoterol passes into breast milk.
Data on the effects on diabetic patients are insufficient.
There may be a slight effect on infants or newborns up to 20 months of age.
Indication
Symptomatic treatment of acute asthma attacks.
Prevention of exercise-induced asthma.
Symptomatic treatment of bronchial asthma of allergic and non-allergic origin and/or other conditions with reversible airway obstruction, such as chronic obstructive bronchitis with and without emphysema.
Long-term therapy should always be accompanied by concomitant anti-inflammatory therapy.
Contraindication
Hypersensitivity to fenoterol hydrobromide or to the excipients of the metered dose aerosol (see section "Composition").
Hypertrophic obstructive cardiomyopathy.
Tachyarrhythmia.
Interaction with other medicinal products and other types of interactions
Concomitant use with other beta-2-adrenergic agents, methylxanthines (e.g. theophylline), anticholinergic agents and corticosteroids may enhance the effect of BEROTEK N. If BEROTEK N is used concomitantly with other beta-2-adrenergic agents, methylxanthines (e.g. theophylline) or systemic anticholinergic agents (pirenzepine-containing agents), increased side effects (e.g. tachycardia, arrhythmia) may occur.
The simultaneous use of BEROTEK N and beta-blockers causes a mutual reduction in effect and the risk of beta-blocker-induced severe bronchospasm in patients with bronchial asthma.
Treatment with BEROTEK H may also reduce the hypoglycaemic effect of antidiabetic medicinal products. However, this is only expected at the high doses usually used for systemic administration (tablets or injections/infusions).
When inhaled halogenated anesthetics such as halothane, methoxyflurane or enflurane, there is an increased risk of severe cardiac arrhythmias and decreased blood pressure in patients using BEROTEK N (see note).
Concomitant use of BEROTEK H and monoamine oxidase inhibitors or tricyclic antidepressants may enhance the effects of fenoterol on the cardiovascular system.
Since hypokalemia may develop with high doses, electrolyte levels should be monitored. This is also particularly important when diuretics and digitalis glycosides are used concomitantly.
Note: If the use of inhaled halogenated anesthetics is planned, it should be taken into account that fenoterol should be discontinued at least 6 hours before the onset of anesthesia.
Application features
BEROTEC N should be used with caution and only as prescribed by a doctor in the following cases: severe heart disease, especially recent myocardial infarction and coronary heart disease, if patients are taking cardiac glycosides, severe and untreated arterial hypertension, aneurysm, hyperthyroidism, poorly controlled diabetes and pheochromocytoma.
Severe hypokalemia may occur during beta-2-agonist therapy. Particular caution is required in severe asthma, as hypokalemia may be potentiated by concomitant administration of xanthine derivatives, glucocorticosteroids, and diuretics. In addition, hypoxia as a symptom of bronchial asthma may enhance the effect of hypokalemia on heart rhythm. In patients receiving digoxin, hypokalemia may lead to an increased susceptibility to arrhythmias. In such conditions, monitoring of serum potassium is recommended.
Attention should be paid to the assessment of symptoms such as dyspnea and chest pain, as they may be of both respiratory and cardiac origin.
Since an increase in blood glucose levels is possible, glucose levels should be monitored in patients with diabetes.
Due to the lack of data on the pharmacokinetics of fenoterol in patients with hepatic and renal insufficiency, the drug should be prescribed with caution to these groups of patients.
The medicine contains ethanol 99% (alcohol; less than 100 mg per dose).
The use of BEROTEC N may give positive results in doping tests.
Use during pregnancy or breastfeeding
Fenoterol penetrates the placental barrier.
The drug should be used during pregnancy only after careful assessment of the benefits and risks, especially during the first trimester of pregnancy.
It is not known whether fenoterol has a negative effect on the infant. Since fenoterol passes into breast milk, the use of the drug during breastfeeding is recommended only after a careful assessment of the benefits and risks.
Despite the fact that the active substance does not exhibit a tocolytic effect when inhaled, the possibility of such a phenomenon cannot be completely ruled out.
There are no clinical data on the effect of fenoterol hydrobromide on fertility. Preclinical studies with fenoterol hydrobromide have shown no adverse effects on fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
No studies on the effects of the drug on the ability to drive and use machines have been conducted. However, patients should be warned about the possibility of undesirable effects such as dizziness during treatment with BEROTEK N. Therefore, caution should be exercised when driving or operating machinery. If the above effects occur, patients should avoid potentially hazardous activities, such as driving or operating machinery.
Method of administration and doses
The dose should be selected depending on the nature and severity of the disease.
The following dosage regimens are recommended for adults and children aged 6 years and over.
For the relief of an acute attack of bronchial asthma and an attack of shortness of breath, inhalation of a dose of 100 mcg of fenoterol hydrobromide (1 inhalation) is recommended.
In general, in an acute attack of shortness of breath, 1 inhalation is sufficient for rapid relief of breathing. If breathing does not improve significantly after 5 minutes of inhalation, a second inhalation may be administered. If there is no effect after 2 inhalations, additional inhalations may be necessary. In such cases, the patient should immediately consult a doctor (see section "Special instructions").
If the use of beta-2-sympathomimetics is deemed necessary for long-term treatment, the recommended dose is 1-2 inhalations of BEROTEC N 3-4 times a day. In general, the time and dose of each application of BEROTEC N should be determined by the frequency and severity of dyspnea (according to symptoms). Treatment should be accompanied by anti-inflammatory therapy, especially in bronchial asthma. There should be an interval of at least 3 hours between inhalations. The total daily dose should not exceed 8 inhalations, and the maximum single dose should not exceed 4 inhalations, since the highest dose does not add therapeutic benefits overall, but may cause severe undesirable effects.
For specific prevention of asthma induced by physical exertion or when contact with an allergen is expected, 1-2 inhalations of BEROTEC N are used, if possible, 10-15 minutes before the expected incident.
For children aged 4-6 years, unless otherwise prescribed, the following dosage regimens are recommended.
For the relief of an acute attack of bronchial asthma and an attack of shortness of breath, inhalation of a dose of 100 mcg of fenoterol hydrobromide (1 inhalation) is recommended.
For long-term treatment or prevention of an attack, 100 mcg (1 inhalation) of fenoterol hydrobromide should be used 4 times a day. The time and dose of each application of BEROTEC N should be determined by the frequency and severity of dyspnea (according to symptoms). Treatment should be accompanied by anti-inflammatory therapy, especially in bronchial asthma. There should be an interval of at least 3 hours between inhalations. The total daily dose should not exceed 4 inhalations, and the maximum single dose should not exceed 2 inhalations, since the highest dose does not add therapeutic benefits overall, but may cause severe undesirable effects.
For specific prophylaxis of exercise-induced asthma or when exposure to an allergen is anticipated, 100 mcg (1 inhalation) of fenoterol hydrobromide should be administered, if possible 10-15 minutes before the anticipated event.
WARNING: If there is no significant improvement or if the condition worsens despite the prescribed treatment, you should consult your doctor to review the treatment plan, possibly combine it with other medications (anti-inflammatory drugs such as corticosteroids, or bronchodilators such as theophylline) or change the dosage. Sudden and progressive worsening of asthma symptoms can be life-threatening. In this case, immediate medical attention is necessary. It is dangerous to use doses that significantly exceed the recommended ones.
Several cases of increased risk of serious complications of the underlying disease, as well as fatalities, have been reported in the long-term treatment of bronchial asthma with excessively high doses of inhaled beta-2-sympathomimetics without adequate anti-inflammatory therapy. The causal relationship has not been fully elucidated. However, inadequate anti-inflammatory therapy plays a vital role.
Special precautions during therapy.
Treatment of bronchial asthma should be gradual and tailored to the severity of the condition. Response to treatment should be monitored regularly.
Unauthorized increase in the dose of beta-2-sympathomimetics, such as BEROTEC N, may be dangerous for the patient.
A sudden and progressive worsening of asthma symptoms can be life-threatening.
An increased need for beta-2-sympathomimetics such as BEROTEC N is a sign of worsening of the condition. In such circumstances, the physician should review the patient's treatment plan and decide whether to prescribe or increase anti-inflammatory therapy or to start additional therapy with other drugs.
From a medical point of view, daily self-monitoring by the patient, as instructed by the doctor, is important to assess disease progression and the success of bronchodilator and anti-inflammatory therapy. This may include recording forced expiratory volume measured with a pneumotachometer.
Instructions for use of metered aerosol.
Correct use of the metered dose inhaler is essential to ensure successful treatment. Patients should be instructed in the correct use of the metered dose inhaler. When inhaling, the arrow on the canister should point straight up and the mouthpiece should point down, regardless of the inhalation position. Use while sitting or standing, if possible.
Before using the can for the first time, press the valve twice.
Procedure before each use:
1. Remove the protective cap (Fig. 1).
Fig. 1. Fig. 2.
2. Exhale completely.
3. Hold the metered dose aerosol as shown in Fig. 2 and place your lips around the mouthpiece. The arrow and base of the container should be facing upwards and the mouthpiece should be facing downwards.
4. Inhale as deeply as possible while pressing firmly on the base of the container, this will release the metered dose. Hold your breath for a few seconds, then remove the mouthpiece and exhale.
If you cannot take a deep breath due to severe shortness of breath, first spray 1 inhalation into the mouth: this will make breathing easier and allow you to apply the medicine correctly.
If another inhalation is required, repeat the above steps (steps 2-4).
5. After use, replace the protective cap.
To prepare for "lung opening" and support aerosol therapy with corticosteroids, saline and disodium cromoglycate, BEROTEK N should be used in advance.
The duration of treatment is determined depending on the nature, severity and progression of the disease. The doctor should select the dose individually.
Additional instructions: Patients should be instructed on the correct use of the metered dose aerosol. Children should only use BEROTEC N metered dose aerosol on the advice of a doctor and under adult supervision.
If the metered aerosol can has not been used for more than 3 days, before use, press the valve once until an aerosol appears.
Clean the inhaler at least once a week.
It is important to keep the inhaler mouthpiece clean to ensure that the medication does not thicken and prevent the aerosol from escaping.
To clean, first remove the dust cap and detach the canister from the inhaler. Rinse the inhaler with water until any thickened medication and/or dirt is removed (Fig. 3).
Fig. 3 Fig. 4
After cleaning, shake the inhaler and leave it to air dry without the aid of any heating system (Fig. 4). When the mouthpiece is dry, attach the container and dust cap.
The plastic mouthpiece is designed specifically for use with BEROTEK N, metered dose aerosol 100 mcg. The mouthpiece should not be used with any other metered dose aerosol. BEROTEK N, metered dose aerosol should only be used with the mouthpiece supplied with the product.
The container is under pressure and must not be opened by force under any circumstances.
The container is opaque. So you can’t see when it’s empty. The aerosol can is supposed to provide 200 doses. When all these doses are used, it may seem like there’s still a little liquid left in the can. However, this can needs to be replaced, otherwise you won’t be able to get the exact amount of medicine.
The amount of medication in an aerosol can can be checked as follows: remove the plastic mouthpiece from the can and place the can in a container of water. The contents of the aerosol can can be estimated by observing its position in the water (see Fig. 5).
Fig. 5.
Used in children aged 4 years and over as prescribed by a doctor and under adult supervision.
Overdose
Symptoms: Depending on the duration of the overdose, the following adverse reactions typical of beta-2-adrenergic agents may occur: flushing, mild dizziness, headache, tachycardia, palpitations, arrhythmia, hypotension or even shock, hypertension, restlessness, chest pain, agitation, possible extrasystole and severe tremor in the fingers and the whole body. Hyperglycemia may develop.
Gastrointestinal reactions, including nausea and vomiting, may occur, especially after oral overdose.
In case of overdose with fenoterol, an increase in the deviation of the level of potassium in the intracellular space may be observed, leading to hypokalemia, hyperglycemia, hyperlipidemia and hyperketonemia. Metabolic acidosis has been observed when fenoterol was used in doses higher than those recommended according to the approved indications for BEROTEK H.
Therapy. Treatment of overdose with beta-sympathomimetics is symptomatic. The effect of fenoterol can be counteracted by beta-blockers. However, it is necessary to take into account the possible increase in bronchial obstruction, so for patients with bronchial asthma it is necessary to carefully select the dose. This also applies to the so-called cardioselective beta-blockers.
Monitoring of cardiac activity, namely ECG, is recommended.
Adverse reactions
Like all medicines, BEROTEK N can cause side effects.
Frequency of adverse reactions:
very common ≥ 1/10;
common ≥ 1/100 < 1/10;
uncommon ≥ 1/1000 < 1/100;
isolated ≥ 1/10,000 < 1/1,000;
rare <1/10,000;
unknown cannot be determined from the available data.
On the part of the immune system:
unknown - hypersensitivity (e.g. itching, rash, purpura, thrombocytopenia, facial edema).
Metabolism and digestion:
uncommon – hypokalemia;
isolated cases – hyperglycemia.
Hypokalemia is more common in patients with severe asthma who are receiving concomitant xanthine derivatives (e.g. theophylline), corticosteroids and/or diuretics. In addition, hypoxia may influence the effect of hypokalemia on heart rhythm. In such cases, monitoring of blood potassium levels is recommended.
Increased blood levels of insulin, free fatty acids, glycerol, and ketone bodies were observed.
Mental disorders:
infrequent – mental disorders, agitation;
unknown – nervousness.
Psychiatric disorders are manifested by increased excitability, hyperactive behavior, sleep disorders and hallucinations. This was observed mainly in children under 12 years of age.
From the nervous system:
frequent – tremor, dizziness;
unknown - headache.
From the side of cardiac activity:
infrequent – arrhythmia, anginal pain, ventricular extrasystole;
not known – tachycardia, palpitations, myocardial ischemia.
From the respiratory system, chest organs and mediastinum:
frequent – cough;
uncommon – paradoxical bronchospasm;
unknown – local irritation.
If paradoxical bronchospasm occurs, treatment should be discontinued immediately.
From the gastrointestinal tract:
frequent – nausea;
infrequent - vomiting, heartburn.
Skin and subcutaneous tissue disorders:
frequent – hyperhidrosis;
infrequent – itching;
not known – urticaria, skin reactions such as rash.
On the part of the musculoskeletal system:
uncommon – muscle spasm;
unknown - muscle weakness, myalgia.
From the kidneys and urinary system:
uncommon – urination disorders.
Research:
uncommon – increased blood pressure, decreased blood pressure.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C. Protect from direct sunlight, heat and frost. Keep out of the reach of children.
Packaging
10 ml (200 doses) in a metal can with a dosing valve in a cardboard box.
Vacation category
According to the recipe.
Producer
Boehringer Ingelheim Pharma GmbH & Co. KG.
Location of the manufacturer and address of its place of business
Binger Strasse 173, D-55216 Ingelheim, Germany.
