Berotec

Fenoterol HBr.

1 metered dose (actuation) contains Fenoterol hydrobromide 100 mcg; Propellant: 1,1,1,2-Tetrafluoroethane (HFA 134a).
Excipients/Inactive Ingredients: Anhydrous citric acid, purified water, absolute ethyl alcohol.

Pharmacology: Berotec is an effective bronchodilator for use in acute asthma and in other conditions with reversible airway narrowing eg, chronic obstructive bronchitis with or without pulmonary emphysema. After oral administration, Berotec acts within a few mins with a duration of action up to 8 hrs.
Following inhalation of fenoterol hydrobromide in obstructive lung diseases, bronchodilatation occurs within a few minutes. The bronchodilator effect lasts 3-5 hrs.
Fenoterol HBr is a direct-acting sympathomimetic agent, selectively stimulating β₂-receptors in the therapeutic dose range. The stimulation of β₁-receptors comes into effect at a higher dose range (eg, as administered in tocolysis). Occupation of β₂-receptors activates adenyl cyclase via a stimulatory G_s-protein. The increase in cyclic AMP activates protein kinase A which then phosphorylates target proteins in smooth muscle cells. This in turn leads to the phosphorylation of myosin light chain kinase, inhibition of phosphoinositide hydrolysis and the opening of large-conductance calcium-activated potassium channels. There is some evidence that the "maxi-K channel" can be directly activated via the G_s-protein.
Fenoterol relaxes bronchial and vascular smooth muscle and protects against bronchoconstricting stimuli eg, histamine, methacholine, cold air and allergen (early response).
After acute administration, the release of bronchoconstricting and pro-inflammatory mediators from mast cells is inhibited. Furthermore, an increase in mucociliary clearance has been demonstrated after administration of doses of fenoterol (0.6 mg).
Higher plasma concentrations, which are more frequently achieved with oral, or even more so with IV administration, inhibit uterine motility. Also at higher doses, metabolic effects are observed: Lipolysis, glycogenolysis, hyperglycaemia and hypokalaemia, the latter caused by increased K⁺-uptake primarily into skeletal muscle. Beta-adrenergic effects on the heart eg, increase in heart rate and contractility, are caused by the vascular effects of fenoterol, cardiac β₂-receptor stimulation and at supratherapeutic doses, by β₁-receptor stimulation. As with other β-adrenergic agents, QTc prolongation has been reported. For fenoterol MDIs, these events were discrete and observed at doses higher than recommended. However, systemic exposure after adminstration with nebulisers (UDVs, solution for inhalation) might be higher than with recommended MDI doses (see Dosage & Administration). The clinical significance has not been established. Tremor is a more frequently observed effect of β-agonists.
In clinical studies, fenoterol was shown to be highly efficacious in manifest bronchospasm. It prevents bronchoconstriction following exposure to various stimuli eg, exercise cold air and the early response following allergen exposure.

Symptomatic treatment of acute asthma attacks; prophylaxis of exercise-induced asthma; symptomatic treatment of bronchial asthma and other conditions with reversible airway narrowing eg, chronic obstructive bronchitis. Concomitant anti-inflammatory therapy should be considered for patients with bronchial asthma and steroid-responsive chronic obstructive pulmonary disease (COPD).

Acute Asthma Episodes: 1 actuation is sufficient for prompt symptom relief in many cases. If an attack has not been relieved by actuations, further actuations may be required.
If an attack has not been relieved by 2 puffs, further puffs may be required. In these cases, patients should consult the doctor or the nearest hospital immediately.
Prophylaxis of Exercise-Induced Asthma: 1-2 actuations for each administration, up to a maximum of 8 actuations per day.
Bronchial Asthma and Other Conditions with Reversible Airways Narrowing: If repeated dosing is required, 1-2 actuations for each administration, up to a maximum of 8 actuations per day. In children should only be used on medical advice and under the supervision of an adult.
Administration: The correct operation of the metered aerosol is essential for successful therapy.
Depress the valve twice before the apparatus is used for the 1st time.
Before each use, the following rules should be observed: Remove protective cap. Breathe out deeply. Hold the metered aerosol and close lips over the mouthpiece. The arrow and the base of the container should be pointing upwards. Breathe in as deeply as possible, pressing the base of the container firmly at the same time, this releases 1 metered dose. Hold breath for a few seconds, then remove the mouthpiece from the mouth and breathe out. If a 2nd inhalation is required, the same action should be repeated. Replace the protective cap after use. After not using the metered aerosol for 3 days, the valve has to be actuated once.
The container is not transparent. It is, therefore, not possible to see when it is empty. The metered-dose aerosol will deliver 200 doses. When these have all been used, the metered-aerosol may still appear to contain a small amount of fluid. The metered-dose aerosol should, however, be replaced because it may not get the right amount of treatment.
The amount of treatment in the metered aerosol can be checked as follows: Remove the metered aerosol from the plastic mouthpiece and put the metered-aerosol into a container of water.
Clean the metered aerosol at least once a week. It is important to keep the mouthpiece of the metered-aerosol clean to ensure that medicine does not build up and block the spray.
For cleaning, first take off the dust cap and remove the canister from the inhaler. Rinse warm water through the metered aerosol until no medication build-up and/or dirt is visible. After cleaning, shake the metered aerosol and let it air-dry without using any heating system. Once the mouthpiece is dry, replace the canister and the dust cap.
Warning: The plastic mouthpiece has been specially designed for use with Berotec 100 mcg to ensure in getting the right amount of the medicine. The mouthpiece must never be used with any other metered aerosol nor must Berotec 100 mcg be used with any mouthpiece other than the one supplied with the product.
The container is under pressure and should by no account be opened by force or exposed to temperatures above 50°C.

Symptoms: Expected symptoms are those of excessive β-adrenergic stimulation, the most prominent being tachycardia, palpitation, tremor, hypertension, hypotension, widening of the pulse pressure, anginal pain, arrhythmias, and flushing.
Metabolic acidosis has also been observed with fenoterol when applied in doses higher than recommended for the approved indications of BEROTEC.
Treatment: Treatment with BEROTEC should be discontinued. Acid base and electrolyte monitoring should be considered.
Administration of sedatives, tranquilizers and in severe cases, intensive therapy may be needed.
Beta-receptor blockers, preferably β₁-selective, are suitable as specific antidotes; however, a possible increase in bronchial obstruction must be taken into account and the dose should be adjusted carefully in patients suffering from bronchial asthma.

Hypertrophic obstructive cardiomyopathy, tachyarrhythmia. Hypersensitivity to fenoterol hydrobromide or to any of the excipients of the product.

Paradoxical bronchospasm: If paradoxical bronchospasm occurs, should be discontinued immediately and substituted with an alternative therapy.
Other sympathomimetic bronchodilators should only be used with Berotec HFA 100 mcg/Berotec Solution 0.1% under strict medical supervision. Anticholinergic bronchodilators may, however, be inhaled at the same time.
In the following conditions, Berotec HFA 100 mcg/Berotec Solution 0.1% should only be used after careful risk/benefit assessment, especially when doses higher than recommended are used: Insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism and phaeochromocytoma.
In the case of acute, rapidly worsening dyspnea (difficulty in breathing), a physician should be consulted immediately.
Prolonged Use: On demand (symptom-oriented) treatment is preferable to regular use. Patients must be evaluated for the addition or the increase of anti-inflammatory therapy (eg, inhaled corticosteroids) to control airway inflammation and to prevent long-term lung damage.
If bronchial obstruction deteriorates, it is inappropriate and possibly hazardous to simply increase the use of β₂-agonist-containing drugs eg, Berotec HFA 100 mcg/Berotec Solution 0.1% beyond the recommended dose over extended periods of time. The use of increasing amounts of β₂-agonist-containing products like Berotec HFA 100 mcg/Berotec Solution 0.1% on regular basis to control symptoms of bronchial obstruction may suggest declining disease control. In this situation, the patient's therapy plan and, in particular, the adequacy of anti-inflammatory therapy, should be reviewed to prevent potentially life-threatening deterioration of disease control.
Potentially serious hypokalemia may result from β₂-agonist therapy. Particular caution is advised in severe asthma, as this effect may be potentiated by concomitant treatment with xanthine derivatives, glucocorticosteroids and diuretics.
Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm. Hypokalaemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin.
It is recommended that serum potassium levels are monitored in such situations.
Cardiovascular effects may be seen with sympathomimetic drugs, including Berotec. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with β-agonists.
Patients with underlying severe heart disease (eg, ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Berotec should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease.
Attention should be paid to the assessment of symptoms eg, dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Effects on the Ability to Drive or Operate Machinery: No studies on the effect on the ability to drive and use machines have been performed. However, patients should be advised that symptoms eg, dizziness have been reported in clinical trials. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience such symptoms, they should avoid potentially hazardous tasks eg, driving or operating machinery.
Impairment of Fertility: Clinical data in fertility are not available for fenoterol. Nonclinical studies performed with fenoterol showed no adverse effect on fertility (see Toxicology).
Use in pregnancy & lactation: Preclinical data, combined with available experience in humans, have shown no evidence of ill effects in pregnancy. Nonetheless, the usual precautions regarding the use of drugs during pregnancy, especially during the 1st trimester, should be exercised.
The inhibitory effect of fenoterol on uterine contraction should be taken into account.
Preclinical studies have shown that fenoterol is excreted into breast milk. Safety during lactation has not been established.

Pregnancy: Preclinical data, combined with available experience in humans, have shown no evidence of ill effects in pregnancy. Nonetheless, the usual precautions regarding the use of drugs during pregnancy, especially during the first trimester, should be exercised.
The inhibitory effect of fenoterol on uterine contraction should be taken into account.
Lactation: Preclinical studies have shown that fenoterol is excreted into breast milk. Safety during lactation has not been established. Caution should be exercised when administered to a nursing woman.
Fertility: Clinical data on fertility are not available for fenoterol. Nonclinical studies performed with fenoterol showed no adverse effect on fertility.

As with all inhalation therapy, Berotec may show symptoms of local irritation.
Immune System Disorders: Hypersensitivity.
Metabolism and Nutrition Disorders: Hypokalaemia including serious hypokalaemia.
Psychiatric Disorders: Agitation, nervousness.
Nervous System Disorders: Tremor, headache, dizziness.
Cardiac Disorders: Myocardial ischaemia, arrhythmia, tachycardia, palpitations.
Respiratory, Thoracic and Mediastinal Disorders (Only Applicable to Inhalative Formulations): Paradoxical bronchospasm, cough, throat irritation.
Gastrointestinal Disorders: Nausea, vomiting.
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis; skin reaction eg, rash, pruritus, urticaria.
Musculoskeletal, Connective Tissue and Bone Disorders: Muscle spasm, myalgia, muscular weakness.
Investigations: Increased systolic blood pressure, decreased diastolic blood pressure.

Beta-adrenergics, anticholinergics and xanthine derivatives (eg, theophylline) may enhance the effect of Berotec. The concurrent administration of other β-mimetics, systemically available anticholinergics and xanthine derivatives (eg, theophylline) may increase the side effects.
Hypokalaemia induced by beta₂-agonists may be increased by concomitant treatment with xanthine derivatives, corticosteroids, and diuretics. This should be taken into account particularly in patients with severe airway obstruction.
A potentially serious reduction in bronchodilation may occur during concurrent administration of β-blockers.
Beta-adrenergic agonists should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of β-adrenergic agonists may be enhanced.
Inhalation of halogenated hydrocarbon anaesthetics eg, halothane, trichloroethylene and enflurane may increase the susceptibility to the cardiovascular effects of β-agonists.

Metered-Dose Aerosol: Store below 30°C.

Antiasthmatic & COPD Preparations

R03AC04 - fenoterol ; Belongs to the class of adrenergic inhalants, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.

G