Ipratropium bromide, fenoterol hydrobromide.
Each puff contains Ipratropium bromide monohydrate equivalent to Ipratropium bromide anhydrous 20 mcg, Fenoterol hydrobromide 50 mcg.
Pharmacotherapeutic Group: Adrenergics and other inhalants used in the treatment of obstructive airway diseases. ATC Code: R03AK03 - fenoterol and other drugs for obstructive airway diseases.
Pharmacology: Pharmacodynamics: Mechanism of Action: AEROBIDOL INHALER contains two active bronchodilating ingredients of Ipratropium bromide, attribute an anticholinergic effect and fenoterol HBr, a selective beta 2-adrenergic agent.
Ipratropium bromide is an anticholinergic (parasympathetic) agent that, based on preclinical studies, appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at neuromuscular junctions in the lung. Anticholinergics prevent the increase in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP), which is caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.
Fenoterol hydrobromide is an adrenergic bronchodilators act by stimulating beta 2-adrenergic receptors in the lungs to relax bronchial smooth muscle, thereby relieving bronchospasm. This action is believed to result from increased production of cyclic adenosine 3,5-monophosphate (cyclic 3,5-AMP; cAMP) and ensuing reduction in intracellular calcium concentration caused by activation of the enzyme adenylate cyclase that catalyzes the conversion of adenosine triphosphate (ATP) to cAMP. Increased cAMP concentrations, in addition to relaxing bronchial smooth muscle, inhibit release of mediators of immediate hypersensitivity from cells, especially from mast cells. Fenoterol hydrobromide has a relatively high degree of selectivity for beta 2-adrenergic receptors.
The combination of Ipratropium bromide and Fenoterol hydrobromide provides the synergistic relief of bronchospasm due to both mechanisms of action for used in bronchial asthma and chronic obstructive pulmonary disease (COPD). The combination will optimize the efficacy of beta-adrenergic portion meanwhile minimize the dosage and undesirable effect. In acute bronchoconstriction, Aerobidol Inhaler is effective shortly after administration and is therefore also suitable for treating acute attacks of asthma.
Pharmacokinetics: Aerobidol Inhaler provides the local therapeutic action in the respiratory tract so the pharmacokinetics of both components do not directly relate to the pharmacodynamics of bronchodilation. The deposited dose in the respiratory tract is around 10-39 % and the other is being swallowed. The pharmacokinetic of each component in the formula is similar to each component separately.
Absorption: Fenoterol HBr: The absolute bioavailability following oral administration is low (approximately 1.5%). Systemic absorption is rapid following aerosol administration; however, serum concentrations at recommended doses are very low or immeasurable. Onset of action of fenoterol is rapid within 5 minutes. Time to peak effect of fenoterol is within 30 to 90 minutes and also 75% of maximal effect is achieved within 5 minutes to product the (FEV 1) occurs within 1 hour after administration. Duration of action is intermediate-acting (3 to 6 hours).
Ipratropium bromide: The absolute bioavailability after oral administration is low (approximately 2%). The bronchodilation following inhalation of ipratropium is primarily a local, site-specific effect, not a systemic one. Much of an administered dose is swallowed but not absorbed, as shown by fecal excretion studies. Ipratropium bromide is absorbed very quickly from the respiratory tract. The peak plasma concentrations are reached only minutes after inhalation. Ipratropium is a quaternary amine. Following nebulization of a 2 mg dose, a mean 7% of the dose was absorbed into the systemic circulation either from the surface of the lung or from the GI tract.
Distribution: Fenoterol HBr: Fenoterol HBr is bound to plasma proteins around 40%. The animal studies suggested that fenoterol and its metabolites do not cross the blood-brain barrier.
Ipratropium bromide: It is not known if the placental barrier is crossed. Ipratropium is minimally bound (0% to 9% in vitro) to plasma albumin and α1-acid glycoprotein. Its blood/plasma concentration ratio was estimated to be about 0.89. Autoradiographic studies in rats have shown that ipratropium does not penetrate the blood-brain barrier.
Metabolism: Fenoterol HBr: After the drug is absorbed, it is mainly metabolized in liver to sulfate conjugates.
Ipratropium bromide: Following intravenous (IV) administration, approximately one half of the dose is excreted unchanged in the urine. The exact metabolic fate of ipratropium bromide has not been fully determined. Following oral or IV administration or oral inhalation, the drug is partially metabolized to at least 8 metabolites. Ipratropium is partially metabolized to inactive ester hydrolysis products. Metabolism appears to involve only the tropic acid moiety and usually consists of hydrolysis and conjugation. The main metabolites appear to be Nisopropylnortropium methobromide, which is formed by enzymatic hydrolysis of the ester; α-phenylacrylic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a water; and phenylacetic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a CH3OH-group. In vitro, these metabolites have minimal or no antimuscarinic activity.
Excretion: Fenoterol HBr: About 15 and 27% of unchanged and metabolites were detected in urine within 24 hours after IV administration but only 1% of unchanged was found after inhalation. The time profiles of the drug in plasma were studied by a 3-compartment model with the terminal half-life is approximately 3 hours. The apparent volume of distribution is about 189 Liters or 2.7 L/kg. Total clearance and renal clearance rate are 1.8 and 0.27 Liter/ minutes, respectively. About 65% or the drug and metabolites are mainly excreted in urine and 14.8% in faeces after IV administration and 39 % in urine with 40.2% in faeces within 48 hours after oral administration.
Ipratropium bromide: Following intravenous (IV) administration, approximately one half of the dose is excreted unchanged in the urine. The half-life of elimination is about 2 hours after inhalation or IV administration. The total body clearance and renal clearance were estimated to be 2,505 and 1,019 mL/min, respectively. The amount of the total dose excreted unchanged in the urine (Ae) within 24 hours was approximately one half of the administered dose. A pharmacokinetic study with 29 COPD patients (48 to 79 years of age) demonstrated that mean peak plasma ipratropium concentrations of 59 ± 20 pg/mL were obtained following a single administration of 4 inhalations of ipratropium HFA inhalation aerosol (84 mcg). Plasma ipratropium concentrations rapidly declined to 24 ± 15 pg/mL by 6 hours. When these patients were administered 4 inhalations 4 times daily (16 inhalations/day = 336 mcg) for 1 week, the mean peak plasma ipratropium concentration increased to 82 ± 39 pg/mL with a trough (6 hour) concentration of 28 ± 12 pg/mL at steady state.
Special Populations: Renal Function Impairment: The pharmacokinetics of ipratropium have not been studied in patients with renal insufficiency. Use with caution in this patient population.
Hepatic Function Impairment: The pharmacokinetics of ipratropium have not been studied in patients with hepatic insufficiency. Use with caution in this patient population.
Elderly: In the pharmacokinetic study with 29 COPD patients, a subset of 14 patients were older than 65 years of age. Mean peak plasma ipratropium concentrations of 56 ± 24 pg/mL were obtained following a single administration of 4 inhalations (21 mcg/puff) of ipratropium HFA inhalation aerosol (84 mcg). When these 14 patients were administered 4 inhalations 4 times daily (16 inhalations/day) for 1 week, the mean peak plasma ipratropium concentration only increased to 84 ± 50 pg/mL indicating that the pharmacokinetic behavior of ipratropium in the geriatric population is consistent with younger patients. Appropriate studies on the relationship of age to the effects of fenoterol have not been performed in the geriatric population. However, no geriatric-specific problems have been documented to date.
Toxicology: Preclinical Safety Data: The studies suggested that the toxicological profiles of HFA and CFC component in the ipratropium bromide and fenoterol hydrobromide formula are similar.
The animal studies have shown the low acute toxicity of the combination ipratropium bromide and fenoterol hydrobromide after oral, IV and inhalation administration the LD50 values of the combination was determined more by the ipratropium bromide than by fenoterol hydrobromide.
The studies in dog and rat suggested that only minor toxic effects such as left ventricular myocardial scars at concentrations up to several hundred times greater than that recommended in man were observed.
The preclinical data has shown all of the adverse effects observed are well known for fenoterol hydrobromide and ipratropium bromide.
No teratogenic effect occurred in animals after inhalation but after oral high dose administration, it induces an increase rate of malformations.
The malformations observed are considered a class effect for beta-agonists but the fertility was not impaired at the therapeutic dose.
Genotoxicity studies for the combination were not performed and no mutagenic potential is caused by both fenoterol hydrobromide and ipratropium bromide.
Carcinogenicity studies for the combination were not performed. No tumorigenic or carcinogenic effects were demonstrated in long term studies in mice and rats with ipratropium bromide, carcinogenicity studies were performed after oral and inhalation administration. At oral doses of 25 mg/kg/day an increased incidence of uterine leiomyomas with variable mitotic activity in mice and mesovarial leiomyomas in rats were observed. These findings are recognized effects caused by the local action of beta-adrenergic agents on the uterine smooth muscle cell in mice and rats. Taking into account present level of research, these results are not applicable to man. All other neoplasias found were considered to be common types of neoplasia spontaneously occurring in the strains used and did not show a biologically relevant increased incidence resulting from treatment with fenoterol hydrobromide.
Metered dose inhaler HFA and metered dose inhaler CFC have been shown to be equally well tolerated in the respiratory tract.
Aerobidol Inhaler is used as a bronchodilator for maintenance treatment of reversible bronchospasm associated with bronchial asthma and chronic obstructive pulmonary disease (COPD) including chronic bronchitis and pulmonary emphysema.
Aerobidol Inhaler is for oral inhalation use only.
General dosing considerations: The dosage should be arranged for the individual requirements; patients should also be kept under medical observation during treatment.
ACUTE ASTHMATIC ATTACK: Adults and Children >6 years: The recommended starting dose is 2 inhalations Aerobidol Inhaler. For patients who require additional symptomatic control; 2 more inhalations may be taken after 5 minutes away from the first inhalations. If the patient needs more than 4 inhalations, or the patient develops a significant decrease in lung function, this may be a marker of destabilization of the disease. In this setting, the patient requires immediate reevaluation with reassessment of the treatment regimen; the patients should consult the doctor or the nearest hospital immediately.
Children under 6 years of age: Safety and efficacy in children under 6 years of age have not been established.
INTERMITTENT AND LONG-TERM TREATMENT: The administration should be used only in asthma attack.
Adults and Children >6 years: The administration of each attack is 1-2 inhalations of Aerobidol Inhaler. The maximum daily dose is 8 inhalations.
Children under 6 years of age: In children, the drug should only be used on medical advice and under the supervision of an adult.
Acute overdose by inhalation is unlikely because ipratropium is not well absorbed systemically after inhalation or oral administration. Oral median lethal doses of ipratropium were greater than 1,000 mg/kg in mice (approximately 20,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis); 1,700 mg/kg in rats (approximately 68,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis); and 400 mg/kg in dogs (approximately 53,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis).
Symptoms: The expected effects of overdosage may be related to fenoterol as excessive beta-adrenergic stimulation, particularly cardiovascular symptoms such as tachycardia, palpitation, tremor, hypertension, hypotension, widening of the pulse pressure, anginal pain, arrhythmias and flushing. The symptoms due to ipratropium bromide (eg, dry mouth, visual accommodation disturbances) are mild because low systemic absorption. Although uncommon fatalities have been reported in association with excessive use of inhaled sympathomimetics. The exact cause of death is unknown. Whether the fatalities are associated with disease severity, substandard quality of care, and/or patient noncompliance has not been established.
Treatment: Monitor the patient carefully, especially for cardiovascular status and supportive care for patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric evaluation. The administration of sedatives, tranquilizers may be necessary in severe cases intensive therapy. Beta1-receptor blockers are specific antidotes but the dosage should be adjusted carefully in patients suffering from bronchial asthma or COPD since it may be increase in bronchial obstruction and risk of severe bronchospasm and fatal.
Hypersensitivity to ipratropium bromide, fenoterol hydrobromide or atropine-like substances, or to any of the excipients of the drug.
Hypertrophic obstructive cardiomyopathy and tachycardia.
The container is under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 50°C may cause bursting. Never throw container into fire or incinerator.
The plastic mouthpiece has been designed for suitable use with Aerobidol Inhaler to ensure the actual amount per actuation. Please do not use any other metered dose inhaler with Aerobidol Inhaler.
Acute Bronchospasm: Inhaled medicines, including the drug, may cause paradoxical bronchospasm. If this occurs, stop treatment and consider other treatments. In the case of acute, rapidly worsening dyspnoea (difficulty in breathing), should consult a physician immediately.
Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of ipratropium as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
Special Risk Patients: The drug should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction, particularly if they are receiving an anticholinergic by another route.
Ocular Effects: There have been isolated reports of ocular complications (ie, difficulty in accommodation, burning eyes, mydriasis, temporary blurred vision, ocular pain, conjunctival or corneal congestion associated with visual halos or colored images, or precipitation or worsening of angle-closure glaucoma) when orally inhaled ipratropium bromide either alone or in combination with an adrenergic beta2-agonist was sprayed into the eyes. Thus, patients must be instructed in the correct administration of the drug. Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist's advice sought immediately.
Cardiovascular Effects: Fenoterol likes all the other sympathomimetic drugs can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Even there is a rare case of myocardial ischemia associated with beta-agonist. The drug should be used with caution in patients with underlying severe heart disease including ischemic heart disease, arrhythmia or severe heart failure.
Hypokalemia: The administration of fenoterol and overdose of beta2-agonist may decrease serum potassium concentration possibly through intracellular shunting. The decrease is dose-related and usually transient.
Prolonged Use: The drug should be used just on asthmatic attack in bronchial asthma and may be regular used in mild Chronic Obstructive Pulmonary Disease. Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
Bronchial Obstruction Deterioration: Increasing use of inhaled, beta-2 agonists is a marker of deteriorating bronchial obstruction; be alert to such changes and advise patients to be alert to such changes. A patient's condition may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient's inhaled, beta-2 agonist becomes less effective, the patient needs more inhalations than usual, or the patient develops a significant decrease in lung function, this may be a marker of destabilization of the disease. In this setting, the patient requires immediate reevaluation with reassessment of the treatment regimen, giving special consideration to the possible need for adding an additional inhaled corticosteroid, or initiating systemic corticosteroids.
Concomitant Administration: The drug should be used with caution when concomitant administration with other sympathomimetic bronchodilators.
Patient with Underlying Diseases: The drug should be used with caution in patient with diabetes mellitus, recent myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism, pheochromocytoma.
Product Interchangeability: Between CFC-containing and HFAcontainingformulations have been interchangeable for all purposeswith having no consequences of the safety or the efficacy.
Effects on the Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. When driving vehicles and operating machinery the possibility of adverse reactions such as dizziness, tremor, accommodation disorder, mydriasis and blurred vision, which may occur in some instances, must be taken into account.
Carcinogenesis: In 2-year oral carcinogenicity studies in rats and mice ipratropium at oral dosages up to 6 mg/kg/day (approximately 240 and 120 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis for the HFA aerosol) showed no carcinogenic activity. Studies to evaluate the carcinogenic, tumorigenic, or mutagenic potential of fenoterol have not been done. There is no evidence from human data that use of these medications may cause problems.
Mutagenesis: Results of various mutagenicity studies with ipratropium (Ames test, mouse dominant lethal test, mouse micronucleus test and chromosome aberration of bone marrow in Chinese hamsters) were negative.
Fertility impairment: Fertility of male or female rats at oral dosages up to 50 mg/kg/day (approximately 2,000 times the maximum recommended human daily inhalation dosage on mg/m2 basis for HFA aerosol) was unaffected by ipratropium administration. At an oral dose of 500 mg/kg (approximately 20,000 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis), ipratropium inhalation HFA aerosol formulation produced a decrease in the conception rate.
Use in Children: The safety and efficacy of orally inhaled ipratropium HFA aerosol in pediatric patients have not been established, although the drug has been used in such patients (generally in children with asthma) with any unusual risk. Appropriate studies on the relationship of age to the effects of fenoterol have not been performed in the pediatric population and also the safety and efficacy of fenoterol in fixed combination with ipratropium bromide for oral inhalation in children have not been established. Therefore, Fenodual inhaler should only be used on medical advice and under the supervision of an adult.
Use in Elderly: No overall differences in safety or efficacy were observed between these subjects and younger subjects. Although not clearly proven, airway responsiveness to these medications may change with age. Additionally, older patients may also be more sensitive to the side effects of beta 2-agonists, including tremor and tachycardia, especially those with preexisting ischemic heart disease. Appropriate studies on the relationship of age to the effects of fenoterol have not been performed in the geriatric population. However, no geriatric-specific problems have been documented to date. When the total number of patients studied in clinical trials of ipratropium HFA inhalation aerosol is considered, 57% were 65 years of age or older. No overall differences in efficacy or safety were observed between geriatric and younger patients in these studies.
Use in Pregnancy: Oral reproduction studies were performed at ipratropium doses of 10 mg/kg in mice, 100 mg/kg in rats, and 125 mg/kg in rabbits. These doses correspond, in each species, respectively, to approximately 200, 40,000, and 10,000 times the maximum recommended human daily inhalation dose of ipratropium on a mg/m2 basis. Inhalation reproduction studies were conducted in rats and rabbits at dosages of 1.5 and 1.8 mg/kg/day (Approximately 60 and 140 times the maximum recommended human daily inhalation dosage on a mg/m2 basis for the HFA aerosol formulation and 38 and 45 times the recommended human daily dosage of ipratropium for the solution). These studies have demonstrated no evidence of teratogenic effects as a result of ipratropium.
At oral doses of 90 mg/kg and above in rats in the aerosol HFA formulation (approximately 3,600 times the maximum recommended daily inhalation dose of ipratropium in adults on a mg/m2 basis) embryotoxicity was observed as increased resorption. This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration.
Adequate and well-controlled studies of fenoterol in humans have not been done. Direct blood and tissue studies in humans showed that the levels of fenoterol and its conjugates were 10 to 20 times lower in the fetus than in maternal tissues. Autoradiographic studies in pregnant rats showed no detectable amounts of fenoterol in the fetus. Direct blood and tissue studies in several animal species showed that levels of fenoterol and its conjugates were 10 to 20 times lower in the fetus than in maternal tissues.
There are no adequate or well controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, use ipratropium and fenoterol during pregnancy only if clearly needed. Nonetheless, the usual precautions regarding the use of drugs during pregnancy, especially during the 1st trimester, should be exercised.
Fenoterol contributes the inhibitory effect on uterine contraction during birth delivery so it should be taken into account.
There are no evidence that the drug affected the fertility but preclinical studies showed no adverse effect on fertility (see Precautions).
Use in Lactation: It is not known whether ipratropium and fenoterol aerosol are excreted in human milk. Although lipidsoluble quaternary cautions pass into breast milk, it is unlikely that the active component, ipratropium, would reach the infant to an important extent, especially when taken by inhalation. Ipratropium is not well absorbed systemically after inhalation or oral administration. However, because many drugs are excreted in human milk, exercise caution when ipratropium and fenoterol are administered to a breast-feeding woman.
Undesirable effects of the product mainly may result from beta-agonist (Fenoterol) and anticholinergic agent (Ipratropium bromide) including local irritation due to other inert and HFA. The most frequent side effects reported in clinical trials were cough, dry mouth, headache, tremor, pharyngitis, nausea, dizziness, dysphonia, tachycardia, palpitations, vomiting, blood pressure systolic increased and nervousness. The following adverse reactions occurred: Immune system disorders:
Anaphylactic reaction, hypersensitivity.
Metabolism and nutritional disorders:
Nervousness, agitation, mental disorder.
Central nervous system disorders:
Headache, tremor, dizziness.
Glaucoma, intraocular pressure increased with precipitate or worsening of narrow-angle glucoma, accommodation disorder, mydriasis, vision blurred, eye pain, corneal oedema, conjunctival hyperaemia, halo vision.
Tachycardia, heart rate increased, palpitations, arrhythmia, atrial fibrillation, supraventricular tachycardia, myocardial ischemia.
Respiratory, thoracic and mediastinal disorders:
Cough, dyspnea, bronchitis, COPD exacerbation, rhinitis, sinusitis, upper respiratory tract infection, pharyngitis, dysphonia, bronchospasm, throat irritation, pharyngeal edema, laryngospasm, bronchospasm paradoxical, dry throat, influenza-like symptoms.
Dyspepsia, vomiting, nausea, dry mouth, stomatitis, glossitis, gastrointestinal motility disorder, diarrhea, constipation, mouth edema.
Skin and subcutaneous tissue disorders:
Urticaria, rash, pruritus, angioeodema, hyperhidrosis, dermatitis.
Musculoskeletal and connective tissue disorders:
Muscular weakness, muscle spasms, myalgia, back pain.
Renal and urinary disorders:
Urinary retention, urinary tract infection.
Blood pressure systolic increased, blood pressure diastolic decreased.
Other beta-agonist, anticholinergics and xanthine derivatives: Concurrent use may enhance the pharmacological effect and adverse reactions.
Beta- adrenergic blocking agents: A potentially serious reduction in bronchodilation may occur during concurrent administration of beta- adrenergic blocking agents as: Ophthalmic beta-adrenergic blocking agents, which are absorbed systemically via the nasolacrimal duct. Respiratory complications associated with the use of timolol have been reported and include bronchospasm, dyspnea, wheezing, decreased pulmonary function, and respiratory failure; therefore, concurrent use may result in inhibition of the betaadrenergic effects of the adrenergic bronchodilators and worsening of bronchospasm).
Systemic beta-adrenergic blocking agents: concurrent use with adrenergic bronchodilators may result in mutual inhibition of therapeutic effects; beta-blockade may antagonize the bronchodilating effect of these bronchodilators; although antagonists with beta1-selectivity may be less antagonistic, extreme caution is recommended if these agents are used in patients with bronchospasm because beta-adrenergic blocking agents may induce bronchospasm.
Corticosteroids, Non potassium-sparing diuretics or Methylxanthines and other xanthine derivatives: Beta-agonist-induced hypokalemia may be increased by concomitant treatment with xanthine derivatives, corticosteroids and diuretics especially in patients with severe asthma. This should be taken into account particularly in patients with severe airway obstruction.
Digoxin: The patients on digitalis glycoside such as digoxin may be more susceptible to arrhythmias due to hypokalemic result when use the drug. Serum potassium level should be monitored periodically.
Monoamine oxidase inhibitors or tricyclic antidepressants: Beta2-agonists containing medicinal products should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or when beta-adrenergic agonists is given within 2 weeks of discontinuing these agents, since the action of beta-adrenergic agonists on the vascular system may be potentiated by these agents.
Halogenated hydrocarbon anesthetics: Beta-agonists should be used with caution in patient during inhalation of halogenated hydrocarbon anesthetics such as halothane, trichloroethylene and enflurane since may increase cardiovascular adverse effects.
Laboratory value alterations: Electrocardiogram: transient ventricular premature contractions, atrial arrhythmia, inverted T waves, junctional rhythm, and prolongation of the QTc interval are reported rarely with adrenergic bronchodilators; effects may be more pronounced following frequent use of higher doses or an overdose; arrhythmias may also result from hypoxia or hypokalemia.
Blood Glucose: Blood glucose concentrations may be increased, possibly due to glycogenolysis; clinically significant changes may be more pronounced following with frequent use of higher doses or an overdose.
Serum Potassium: serum potassium concentrations may be decreased, possibly through intracellular shunting; the decrease is dose-related, is usually transient, and may not require supplementation; effects may be more pronounced following with frequent use of higher doses or an overdose.
Handling precaution: Avoid spraying in eyes.
Contents under pressure: Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 50°C may cause bursting. Never throw container into fire or incinerator.
Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use. SHAKE WELL BEFORE EACH SPRAY.
It does not contain chlorofluorocarbons (CFCs) as the propellant.
Store below 30°C. Keep in tight containers, protected from light.
Information for the patient: For instructions on the proper use of Aerobidol Inhaler and to attain the maximum improvement in asthma symptoms, the patient or the parent/ guardian of the patient should receive, read, and follow the accompanying patient information and instructions carefully. In addition, patients being treated with Aerobidol Inhaler should receive the following information and instructions. This information is intended to aid the patient in the safe and effective use of the medication. It is not a disclosure of all possible adverse or intended effects.
Aerobidol Inhaler should be stored upright at controlled room temperature 20° to 25°C (68° to 77°F) and protected from light. Aerobidol Inhaler should not be refrigerated or frozen.
Do not use the inhalation more frequently than recommended. The dose or frequency of the inhalation aerosol should not be increased without patients consulting their doctors. If treatment with the inhalation aerosol becomes less effective for symptomatic relief, their symptoms become worse, and/or patients need to use the product more frequently than usual, seek medical attention immediately.
Advise patients who are pregnant or breast-feeding to contact their doctors about the use of the inhalation. Appropriate use of the inhalation includes an understanding of the way it should be administered.
Instruct patients to avoid spraying ipratropium in or around the eyes. Caution patients to avoid spraying the aerosol into their eyes and advise them that this may result in precipitation or worsening of narrow-angle glaucoma, mydriasis, eye pain or discomfort, temporary blurring of vision, visual halos, or colored images in association with red eyes from conjunctival and corneal congestion. Advise patients that should any combination of these symptoms develop, they should consult their doctors immediately.
While taking the inhalation aerosol, other inhaled drugs should not be used unless prescribed.
Remind patients that the inhalation should be used consistently as prescribed throughout the course of therapy.
Read the following text carefully before you start to use.
The parts of your inhaler: There are 2 main parts to your inhaler the metal canister that holds the medicine and the plastic actuator that sprays the medicine from the canister.
The inhaler also has a dust cap that covers the mouthpiece of the actuator.
Do not use the actuator with a canister of medicine from any other inhaler. And do not use with an actuator from any other inhaler.
How to use your inhaler: Testing your inhaler: 1. When using the inhaler for the first time, test that it is working. Remove the mouthpiece cover by gently squeezing the sides with your thumb and forefinger and pull apart.
2. Point the mouthpiece away from you and press the canister to release a puff into the air. If you have not used the inhaler for more than 3 days, release two puffs of medicine into the air.
Using your inhaler: It is important to start to breathe as slowly as possible just before using your inhaler. 1. Stand or sit upright when using your inhaler.
2. Remove the mouthpiece cover. Check inside and outside to make sure that the mouthpiece is clean and free of objects.
3. Depress the valve twice (if the inhaler has not been for more than 3 days the valve has to be actuated once to twice).
4. Hold the inhaler upright with your thumb on the base, below the mouthpiece. Breathe out as far as is comfortable. Do not breathe in again yet.
5. Place the mouthpiece in your mouth between your teeth. Close your lips around it. Do not bite.
6. Breathe in through your mouth. Just after starting to breathe in, press down on the top of the canister to release a puff of medicine. Do this while still breathing in steadily and deeply.
7. Hold your breath, take the inhaler from your mouth and your finger from the top of the inhaler. Continue holding your breath for a few seconds, or as long as is comfortable.
8. If your doctor has told you to take two puffs, wait about half a minute before you take another puff by repeating steps 3 to 7.
9. After use always replace the mouthpiece cover straight away to keep out dust. Replace the cover by firmly pushing and clicking into position.
Cleaning your inhaler: To stop your inhaler blocking, it is important to clean it at least once a week.
To clean your inhaler: Remove the mouthpiece cover.
Do not remove the metal canister from the plastic casing at any time.
Wipe the inside and outside of the mouthpiece and the plastic casing with a dry cloth or tissue.
Replace the mouthpiece cover.
Do not put the metal canister in water.
R03AL01 - fenoterol and ipratropium bromide ; Belongs to the class of combination of adrenergics with anticholinergics, that may also include a corticosteroid. Used in the treatment of obstructive airway diseases.
MDI (CFC-free) 200 doses.