BEROTEC® Inhalation Aerosol BEROTEC® FORTE Inhalation Aerosol
Action And Clinical Pharmacology: The bronchodilating effect of fenoterol is produced primarily by stimulation of b2 receptors in the bronchial smooth muscles. The effect has been measured by means of spirometry (FEV1, FVC, MMFR), peak flow rates, flow volume curves, airway resistance (plethysmography) and oscillation mechanics.
Fenoterol, when administered by inhalation, exerts a significant increase in pulmonary function 5 minutes after administration and maximal effect in 30 to 60 minutes. This effect remains at the same level for 2 to 3 hours before gradually declining. A significant degree of bronchodilation has been detected in some studies for 6 to 8 hours.
Pharmacokinetics: In man, fenoterol is rapidly absorbed from the gastrointestinal tract, with an absorption level of 60%. After administration of tritium labelled fenoterol, peak plasma levels (2.5% of the oral dose) are reached in 2 hours, the half-life of radioactivity being 6 to 7 hours. When given from a pressurized container, absorption proceeds in 2 phases: the first one is essentially independent of the dose and apparently takes place between the first and fourth subdivision of the bronchial tree. A second phase appears to be identical to oral absorption. After inhalation, blood levels remain almost unchanged for 7 hours (0.3 to 0.4 ng/mL fenoterol).
Following i.v. administration, fenoterol is very rapidly taken up by the tissues where it is conjugated to the extent of 99% (as sulfates). Unlike isoproterenol, fenoterol is not metabolized by catechol-O-methyl transferase. The resulting metabolites are excreted via the kidneys (40% within 48 hours after oral administration) and the bile (fecal excretion: 40% of the oral dose).
Autoradiographic studies in gravid rats showed no detectable amounts of fenoterol in the fetus. Direct blood and tissue studies in several animal species and in man showed that the levels of fenoterol and its conjugates were 10 to 20 times lower in the fetus than in the maternal tissues.
Indications And Clinical Uses: For the symptomatic relief and acute prophylaxis of bronchial obstruction in asthma and other conditions in which reversible bronchospasm is a complicating factor, such as chronic bronchitis or emphysema.
Contra-Indications: Like other sympathomimetic amines, fenoterol inhalation aerosols should not be used in patients with tachyarrhythmias, hypertrophic obstructive cardiomyopathy or in patients with known hypersensitivity to fenoterol or to any of the product components (see Supplied).
Manufacturers’ Warnings In Clinical States: Like other b2 agonists inhalers, fenoterol should not be used on a regular basis without appropriate concomitant anti-inflammatory therapy (see Dosage).
Children: Not currently indicated for use in children under 12 years of age as the dosing regimen and evidence concerning its safety in this age group have not been established.
Pregnancy and Lactation: The safety of fenoterol in pregnancy and lactation has not been established. b2 agonists should be used with caution before childbirth in view of their inhibiting effect on uterine contractions.
General: Care should be taken in patients suffering from myocardial insufficiency, cardiac arrhythmias, recent myocardial infarction, severe organic heart and/or other vascular disorders, hypertension, hyperthyroidism or diabetes mellitus.
Fatalities, the exact cause of which is unknown, have been reported following excessive use of sympathomimetic amines by inhalation. Cardiac arrest was noticed in several instances.
Some patients receiving inhaled b-adrenergic agonists have developed severe paradoxical bronchospasm, which has been life-threatening. The cause of this refractory state is unknown. If it occurs, the preparation should be discontinued immediately and alternative therapy instituted.
In common with other b-adrenergic agents, fenoterol can induce reversible metabolic changes. These are most pronounced during infusions of the drug and include hyperglycemia and hypokalemia.
Potentially serious hypokalemia may result from b2-agonist therapy, mainly from parenteral and nebulized administration. Particular caution is advised in acute severe asthma as hypokalemia may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics; the adverse effects of hypokalemia may be exacerbated by hypoxia. It is recommended that serum potassium levels be monitored in such situations. Hypokalemia will increase the susceptibility of digitalis-treated patients to cardiac arrhythmias.
The bronchodilating action of sympathomimetic drugs may be antagonized by b-adrenergic blocking agents with the result that the respiratory status of patients may worsen when the 2 drugs are used concomitantly. In patients requiring concomitant treatment with fenoterol inhalation aerosols and a b-adrenergic blocking agent, the use of a relatively cardioselective b-blocker (e.g., metoprolol, atenolol, acebutolol) must be considered. During concomitant treatment, patients must be monitored carefully for possible deterioration in pulmonary function or for the need to adjust the dosage of either drug.
Precautions: General: If therapy does not produce a significant improvement or if the patient’s condition gets worse, medical advice must be sought in order to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnea, a doctor should be consulted immediately.
Increasing use of b2 agonists to control symptoms of bronchial obstruction, especially administration on a regular basis or in high amounts, indicates deterioration of asthma control. Under these conditions, the patient’s therapy plan has to be revised. It is inadequate simply to increase the use of bronchodilators under these circumstances, in particular over extended periods of time (see Dosage).
Concomitant use of fenoterol inhalation aerosols with other sympathomimetic agents is not recommended since the combined use may lead to deleterious cardiovascular effects. If concomitant use is necessary, this should take place only under strict medical supervision.
Fenoterol should be used with caution in asthmatic or emphysematous patients who also have acute and recurring congestive heart failure or glaucoma or in patients sensitive to sympathomimetic amines.
Like other pressurized aerosol formulations, fenoterol inhalation aerosols contain fluorocarbon propellants (monofluorotrichloromethane, tetrafluorodichloroethane and difluorodichloromethane). Such propellants may be hazardous if they are deliberately abused. Inhalation of high concentrations of aerosol sprays has brought about toxic cardiovascular effects and even death, especially under conditions of hypoxia. However, evidence attests to the relative safety of aerosols when used properly and with adequate ventilation. The recommended dose of fenoterol inhalation aerosol should not be exceeded and the patient should be so informed.
Three retrospective case-control studies, from one group in New Zealand, have suggested that there may be an increased risk of death in those patients using fenoterol whom the studies classified as severe asthmatics. These conclusions have not been confirmed by other studies and are subject to considerable debate and ongoing studies.
To ensure the proper dosage administration, the patient should be instructed by the physician or other health professional in the use of the inhaler.
Drug Interactions: Other b-adrenergic agents, anticholinergics, xanthine derivatives and corticosteroids may enhance the effect of fenoterol inhalation aerosol. Avoid concomitant use of fenoterol with monoamine oxidase inhibitors, tricyclic antidepressants or with other sympathomimetic agents since their combined effect on the cardiovascular system may be deleterious to the patient.
Beta-receptor blocking agents and fenoterol inhibit the effect of one another (see Warnings).
Labor and Delivery: Beta-adrenergic agents have been shown to delay preterm labor in some reports. There are no well controlled studies which demonstrate that such agents will stop preterm labor or prevent labor at term. Cautious use of b-adrenergics for the relief of bronchospasm is therefore required in pregnant patients to avoid interference with uterine contractility.
Adverse Reactions: The following adverse reactions have been reported at therapeutic dosage levels of fenoterol inhalation aerosols: tremor, restlessness, palpitations, dizziness, headache, nausea, lightheadedness and weakness. Other occasional reactions include vomiting, heartburn, sweating, nervousness, bad taste, fatigue, prickling and tingling sensations over the body, and agitation. Local irritation or allergic reactions have been reported rarely. As with other bronchodilators, cough and, very rarely, paradoxical bronchospasm have been observed (see Warnings). Potentially serious hypokalemia may result from b2 agonist therapy.
Symptoms And Treatment Of Overdose: Symptoms: Overdosage resulting in excessive b-adrenergic stimulation may cause tachycardia, cardiac arrhythmia, hypertension and, in extreme cases, sudden death.
Treatment: Symptomatic: Cardiac and respiratory support should be provided as required. If needed, to antagonize the effect of b-adrenergic stimulation, the use of a cardioselective b-adrenergic blocking agent, (e.g., metoprolol, atenolol, acebutolol) may be considered, bearing in mind however the potential danger of inducing an asthmatic attack.
Dosage And Administration: Dosage should be individualized, and patient response should be monitored by the prescribing physician on an ongoing basis.
Berotec (100 g): Acute Symptoms: 1 puff will usually be adequate to relieve bronchospasm in the majority of patients, however, if required, a second puff may be taken preferably after waiting 5 minutes for the effect of the first puff to be obtained. This delay allows better assessment of the effectiveness of 1 puff and deeper penetration of the second puff.
If an attack has not been relieved by 2 puffs, further puffs may be required. In these cases, patients should immediately consult the doctor or the nearest hospital.
If, despite other adequate maintenance therapy, regular use of beta-agonists remains necessary for the control of bronchospasm, the recommended dose is 1 to 2 puffs of Berotec 100 Âµg 3 to 4 times daily. A maximum of 8 puffs/day should not be exceeded.
Berotec forte (200 g): Acute symptoms: 1 puff should be adequate to relieve bronchospasm in the majority of patients. However, if required, a second puff may be taken, preferably after waiting 5 minutes for the effect of the first puff to be obtained. This dose of 1 or 2 inhalations may be repeated up to 3 times daily. Doses should not be taken more often than every 4 hours.
If an attack has not been relieved by 2 puffs, the patient should immediately consult the doctor or the nearest hospital.
If a previously effective dosage regimen fails to provide the usual relief, or the effects of a dose last for less than 3 hours, medical advice should be sought immediately; this is a sign of worsening asthma that requires reassessment of therapy.
Intermittent and Long-Term Treatment: Generally, long-term treatment with beta-agonists in bronchial asthma should be on demand, e.g., symptoms orientated.
Patients must not use them on a daily regular basis without using other concomitant anti-asthma medication(s) according to the present practice for asthma treatment to control airway inflammation.
The regular daily dose of fenoterol should not be increased without adequate reassessment of the therapy plan.
As with other beta-agonists increasing demand for fenoterol in bronchial asthma is a sign of poor asthma control and indicates that the treatment plan should be revised.
Stability and Storage: The aerosol canister should be stored at room temperature (15 to 30°C); the contents are stable up to the expiration date stamped on the label. Caution. Contents under pressure. Do not place in hot water or near radiators, stoves, or other sources of heat. Do not puncture or incinerate container or store at temperatures over 30°C.
Availability And Storage: Berotec (100 g) and Berotec forte (200 g) are metered dose aerosol systems which contain a suspension of fenoterol HBr in fluorocarbon propellants (difluorodichloromethane, monofluorotrichloromethane, tetrafluorodichloroethane) with sorbitan trioleate as a dispersing agent.
Berotec (100 g): Each valve depression (actuation) delivers 100 g of fenoterol HBr as a micronized powder. Each canister is designed to deliver at least 200 metered doses.
Berotec forte (200 g): Each valve depression (actuation) delivers 200 g of fenoterol HBr as a micronized powder. One canister size for hospital use only, is designed to deliver at least 100 metered doses.
BEROTEC® Inhalation Aerosol BEROTEC® FORTE Inhalation Aerosol Boehringer Ingelheim Fenoterol HBr Bronchodilator