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DUOVENTŪ UDV
Boehringer Ingelheim
Ipratropium Bromide - Fenoterol Hydrobromide
Bronchodilator
 
Action And Clinical Pharmacology: Duovent UDV inhalation solution is a combination of the anticholinergic bronchodilator ipratropium bromide and the beta2-adrenergic bronchodilator fenoterol hydrobromide. Ipratropium is a quaternary ammonium derivative of atropine and is an anticholinergic drug which has bronchodilator properties. On inhalation of ipratropium the onset of action is noted within 5 to 15 minutes with a peak response between 1 and 2 hours, lasting about 2 additional hours with subsequent decline from the peak. Bronchodilation is still evident 8 hours after inhalation.

The bronchodilating effect of fenoterol is produced primarily by stimulation of b2 receptors in the bronchial smooth muscles. When administered by inhalation, fenoterol exerts a significant increase in pulmonary function 5 minutes after administration with a 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 reported in some studies for 6 to 8 hours.

The concurrent administration of ipratropium and fenoterol results in dilatation of the bronchi by affecting different pharmacologic sites of action.

Pharmacokinetics: The pharmacokinetics of ipratropium and fenoterol are not altered when the 2 drugs are administered concurrently.

Indications And Clinical Uses: For the symptomatic relief of bronchospasm associated with acute severe exacerbations of bronchial asthma or chronic obstructive pulmonary disease (COPD).

Duovent UDV inhalaton solution must be administered by means of nebulizer using gas flow (oxygen or compressed air).

Contra-Indications: Should not be used by patients with tachyarrhythmias, hypertrophic obstructive cardiomyopathy, or by those with a known sensitivity to the component drugs, sympathomimetic amines, atropinics or to any of the product components. tag_WarningWarnings

Manufacturers' Warnings In Clinical States: Like other inhalation solutions that contain b2 agonists, Duovent UDV should not be used on a regular basis without appropriate concomitant anti-inflammatory therapy (see Dosage).

Children: Duovent UDV is 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 Duovent UDV in pregnancy and lactation has not been established. It should be used with caution before childbirth in view of the inhibiting effect of b2 agonists 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 Duovent UDV and a b-adrenergic blocking agent, the use of a relatively cardioselective b-blocker (e.g., metoprolol, atenolol, acebutolol) must be considered. During the concomitant treatment, patients should be monitored carefully for possible deterioration in pulmonary function or for the need to adjust the dosage of either drug.

Glaucoma, Angle-Closure: Care should be taken to ensure that the nebulizer mask fits the patient's face properly and that nebulized solution does not escape into the eyes (i.e., use swimming goggles). In patients with glaucoma or narrow anterior chambers, the administration by nebulizer of Duovent UDV should be avoided unless measures (e.g., use of swimming goggles) are taken to ensure that nebulized solution does not reach the eye. Exposure of the eyes of such patients to a nebulized combination of ipratropium and a b2 agonist solution (i.e., Duovent UDV) has been reported to result in increased intraocular pressure and/or acute angle closure. There have been isolated reports of ocular complications (i.e., mydriasis, increased intraocular pressure, angle closure glaucoma) when nebulized ipratropium either alone or in combination with an adrenergic b2 agonist solution has escaped into the eyes. In the event that glaucoma is precipitated or worsened, treatment should include standard measures for this condition.

Use of Duovent UDV in Conjunction with IPPV: It has been reported in several cases that the use of intermittent positive-pressure ventilation in acute asthma attacks was related to lethal episodes of hypoxia and pneumothorax. This method of drug administration may be ineffective in patients with severe obstruction and greatly increased airway resistance and it may induce severe hypercapnia and hypoxia. During intermittent positive-pressure ventilation therapy, the monitoring of arterial blood gases is highly desirable.

Precautions: 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 Duovent UDV 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.

Caution is advised against accidental release of the solution into the eyes.

Duovent UDV should be used with caution in patients with glaucoma, prostatic hypertrophy or urinary retention and in asthmatic or emphysematous patients who also have acute and recurring congestive heart failure or in patients sensitive to sympathomimetic amines.

Failure to respond to a previously effective dose usually indicates a significant deterioration in the patient's asthmatic condition. The patient should be instructed to contact his/her physician immediately in these circumstances and warned on no account to exceed the recommended dose.

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 on the proper use and maintenance of the nebulizer.

Drug Interactions: Other b-adrenergic agents, anticholinergics, xanthine derivatives and corticosteroids may enhance the effect of Duovent UDV inhalation solution. Avoid concomitant use of Duovent UDV with MAO 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).

In patients receiving other anticholinergic drugs, Duovent UDV should be used with caution because of possible additive effects.

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: Frequent undesirable effects of Duovent UDV are fine tremor of skeletal muscles and nervousness, less frequent are tachycardia, dizziness, palpitations or headache, especially in hypersensitive patients.

In isolated cases there may be local reactions such as dryness of the mouth, throat irritation, or allergic reactions. As with other bronchodilators, in some cases cough, in very rare instances paradoxical bronchoconstrictions have been observed.

The adverse reactions noted for the individual components of Duovent UDV inhalation solution are as follows:

Ipratropium: The frequency of adverse reactions recorded in 214 patients receiving ipratropium solution was as follows given by adverse effect (% of patients): dry mouth or throat (9.3); bad taste (5.1); tremor (4.2); exacerbation of symptoms (4.2); burning eyes (0.9); nausea (0.9); sweating (0.9); cough (0.9); headache (0.5); palpitations (0.5).

The adverse effect judged to be most severe was exacerbation of symptoms. This occurred in 8 patients treated with ipratropium solution alone, 6 of whom withdrew from the clinical studies.

Bronchospasm occurred in 3 patients with acute severe asthma who received ipratropium solution alone. In 2 patients, this was reversed after therapy with a b2 sympathomimetic solution. The third patient received no other therapy.

Table I compares the incidence of adverse effects of the combination of ipratropium and a b2 agonist solution with that of the b2 agonist alone.

There have been isolated reports of ocular effects such as mydriasis, increased intraocular pressure, and acute glaucoma associated with the escape of nebulized ipratropium alone or in combination with a b2 agonist solution into the eyes.

Fenoterol: At the most frequently used dosage of fenoterol solution of 0.5 to 1 mg, temor occurred in 12% of patients. At higher doses of fenoterol solution (up to 2.5 mg) given for the treatment of severe asthma in a hospital emergency room, mild to moderate tremor occurred in 32% of patients. Other adverse reactions in decreasing order of frequency included nervousness, dizziness, headache, lightheadedness, and palpitations.

In 104 patients who received the highest recommended dosage of 2.5 mg of fenoterol solution, increases in heart rate of 10% or greater within 4 hours after drug administration were observed in 21% of the patients. However, at least an equal number of patients had decreased heart rate of a similar magnitude in the same time period. The remainder showed no significant pulse rate changes.

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 and Treatment: Overdosage resulting in excessive b-adrenergic stimulation may cause tachycardia, arrhythmia, hypertension and in extreme cases, sudden death. If Duovent UDV overdosage occurs, cardiac and respiratory support should be provided as required. tag_DosageDosage

Dosage And Administration: COPD: Chronic Bronchitis and Emphysema: Duovent UDV inhalation solution dosage should be individualized, and patient response should be monitored to determine the requirement for more than a single bronchodilator by the prescribing physician on an ongoing basis.

Counselling on smoking cessation should be the first step in treating patients with chronic bronchitis who smoke. Smoking cessation produces symptomatic benefits and has been shown to confer a survival advantage by slowing or stopping the progression of chronic bronchitis and emphysema.

Asthma: Duovent UDV inhalation solution should be used only under medical supervision in patients with severe acute exacerbations of asthma who require more than a single bronchodilator.

In accordance with the present practice for asthma treatment, concomitant anti-inflammatory therapy should be part of the regimen if Duovent UDV needs to be used on a regular daily basis.

If a previous 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 seriously worsening asthma that requires reassessment of therapy.

Dosage And Administration: Adults and children 12 years of age or over: The usual dose is 4 mL of Duovent UDV inhalation solution. Treatment may be repeated after 6 hours when necessary.

Not recommended for children under 12 years of age.

Dilution Instructions: If the full content of Duovent UDV is to be nebulized, squeeze the plastic vial to empty its contents into the nebulizer chamber. If instructions were given to use a dose less than 1 complete vial, use a syringe to transfer the necessary amount to the nebulizer chamber. Any solution left in the plastic vial must be discarded because Duovent UDV does not contain preservatives. Use a syringe to add sterile, preservative-free 0.9% sodium chloride solution to the nebulizer chamber. Sodium chloride solution may be added to fill the nebulizer solution to a maximum of 5 mL.



Availability And Storage: Each mL of clear, colorless solution contains: ipratropium bromide 0.125 mg and fenoterol hydrobromide 0.3125 mg. Nonmedicinal ingredients: hydrochloric acid, purified water and sodium chloride. Plastic single use vials of 4 mL, cartons of 20.

Unopened unit dose vials should be stored at controlled room temperature (15 to 25°C) and protected from light. If necessary, the solution may be diluted with preservative-free sterile sodium chloride solution 0.9% and used immediately. Any solution remaining in the vial must be discarded.