Ipratropium bromide is used for the symptomatic treatment of reversible bronchospasm that may occur in association with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Ipratropium bromide in fixed combination with albuterol sulfate is used by oral inhalation for the symptomatic management of bronchospasm associated with COPD in patients who continue to have evidence of bronchospasm despite the regular use of an orally inhaled bronchodilator and who require a second bronchodilator. Ipratropium bromide also is used for the symptomatic treatment of bronchial asthma and for the prevention of exercise-induced bronchospasm, and also has been used as a bronchodilator in patients with cystic fibrosis.
Chronic Obstructive Pulmonary Disease
Ipratropium bromide is used as a bronchodilator for the long-term symptomatic treatment of reversible bronchospasm associated with COPD, including chronic bronchitis and emphysema. Orally inhaled ipratropium is not indicated as a single agent for the initial treatment of acute episodes of bronchospasm or acute exacerbations of COPD; a drug with a more rapid onset of action (e.g., a β2-adrenergic agonist) may be preferred in such cases.
(See Cautions: Precautions and Contraindications.)However, some clinicians consider combined therapy with a β2-agonist bronchodilator and ipratropium to be useful in selected patients with acute exacerbations of COPD.
The efficacy of ipratropium has been similar to or greater than that of β2-adrenergic agonists (e.g., albuterol, metaproterenol) in comparative studies in which these drugs were administered via metered-dose inhaler or nebulization. As orally inhaled ipratropium produces fewer adverse effects than these drugs, ipratropium is a first-line maintenance bronchodilator for relief of chronic (e.g., daily) symptoms of bronchospasm in patients with mild COPD. However, in a few long-term studies comparing ipratropium bromide and tiotropium bromide, another long-acting orally inhaled anticholinergic agent, ipratropium bromide (36 mcg 4 times daily) oral inhalation aerosol with chlorofluorocarbon (CFC) propellants (preparation with CFC propellants no longer commercially available in the US) was less effective than tiotropium (18 mcg once daily) in improving lung function (e.g., as determined by changes in forced expiratory volume in 1 second [FEV1] and peak expiratory flow rate [PEFR]) in patients with COPD. Short-term (e.g., 3-month) controlled studies indicate that the fixed combination of albuterol and ipratropium results in greater bronchodilation following oral inhalation than either agent given alone in patients with COPD.
The efficacy and safety of ipratropium bromide with a hydrofluoroalkane propellant (Atrovent HFA) have been shown to be comparable to that of ipratropium bromide with chlorofluorocarbon propellants (Atrovent, no longer commercially available in the US) in patients with COPD. In 2 randomized, comparative clinical trials in patients with COPD, therapy with ipratropium bromide inhalation aerosol with a hydrofluoroalkane (HFA) propellant (Atrovent HFA 34 or 68 mcg [dose delivered from the mouthpiece] 4 times daily) produced similar improvements in FEV1 and forced vital capacity (FVC) over the 12-week study period and had similar adverse effects as therapy with ipratropium bromide with chlorofluorocarbon propellants (Atrovent 36 mcg [dose delivered from the mouthpiece] 4 times daily). In one of these studies, the mean peak improvement in FEV1 relative to baseline on day 85 of therapy (one of the primary end points) was 0.295 L after a single dose of Atrovent HFA (34 mcg or 2 inhalations) compared with 0.14 L observed with placebo (HFA propellant vehicle only).
Administration of nebulized ipratropium generally is reserved for patients with severe disease who do not respond adequately to conventional therapy and for those who find it difficult or are unable to optimally inhale the drug orally via a metered-dose inhaler.
In the stepped-care approach to COPD drug therapy, mild intermittent symptoms and minimal lung impairment (e.g., FEV1 at least 80% of predicted) can be treated with a short-acting selective inhaled β2-agonist as needed during acute exacerbations, but use should not exceed 8-12 inhalations daily. Alternatively, some clinicians initiate therapy with ipratropium inhalation aerosol. Patients with COPD who receive orally inhaled ipratropium generally have an increase in FEV1 (at its peak) of 0.15-0.36 L and a decrease in functional residual capacity of 0.3-0.6 L. Although ipratropium produces objective bronchodilation (i.e., increase in FEV1 and FVC) in patients with COPD, a beneficial effect on subjective symptom or quality-of-life scores has not been demonstrated in short-term (e.g., 3-month) clinical studies, and current evidence indicates that ipratropium therapy does not alter the disease process (neither accelerates nor slows the age-related decline in FEV1 associated with COPD).
Low- to high-dose ipratropium bromide (6-16 inhalations daily) can be added to therapy with a selective β2-agonist in patients with mild to moderate symptoms of COPD, with the frequency of inhalation dosing with either agent not to exceed 4 times daily; the highest dosage of ipratropium bromide included in some guidelines for COPD exceeds the manufacturer's recommended maximum daily dosage (12 inhalations). Therapy with anticholinergic and/or β2-adrenergic agonist bronchodilators increases airflow and exercise tolerance and reduces dyspnea in patients with symptoms of COPD, and these drugs are used in the long-term management of airflow limitation in such patients. The mean peak FEV1 increase was 0.37 L following short-term (approximately 3 months) administration of the fixed combination of albuterol sulfate (180 mcg as albuterol base) and ipratropium bromide monohydrate (36 mcg) 4 times daily. The fixed combination of ipratropium and albuterol did not affect morning PEFR after short-term administration (i.e., less than 3 months) in these patients.
Current evidence indicates that concomitant or sequential administration of inhaled ipratropium and an inhaled β2-adrenergic agonist in patients with COPD generally produces additional bronchodilation compared with that achieved with either agent alone. Although the improvement in bronchodilation produced by combined therapy with ipratropium and a β2-adrenergic agonist often may not exceed that which could be achieved with larger dosages of either agent alone, the duration of bronchodilation appears to be increased with such concomitant therapy, and the potential for adverse effects also may be minimized. The sequence of administration of ipratropium and a short-acting β2-agonist generally does not alter the effectiveness of the bronchodilating action.
Home management of COPD exacerbations involves increasing the dose and/or frequency of existing short-acting bronchodilator therapy, preferably with a B2-adrenergic agonist. If response to a short-acting β2-adrenergic agonist alone is inadequate, some clinicians recommend the addition of ipratropium. In a severe exacerbation treated at home, administration of these agents by nebulization or metered-dose inhalation with a spacer device may be used as needed for short-term therapy.
Following initiation of oxygen therapy in hospitalized patients with COPD, therapy with a short-acting β2-adrenergic agonist and/or ipratropium (administered separately or in fixed combination) should be used for acute exacerbations of COPD, although the effectiveness of such combination therapy remains controversial.
Orally inhaled ipratropium bromide has been used effectively for the symptomatic treatment of acute or chronic bronchial asthma and can potentiate the bronchodilatory effects of β2-adrenergic agonists, but the precise role of the drug in the management of this condition remains to be more fully elucidated. Ipratropium is suggested by some experts as an alternative to short-acting inhaled β2-agonists for relief of asthma symptoms, particularly in patients who experience adverse effects with β2-adrenergic agonists. However, the efficacy of ipratropium in the long-term management of asthma has not been established. Because the onset of action of ipratropium is slower than that of β2-adrenergic agonist bronchodilators and the peak bronchodilator effects generally are less pronounced, β2-adrenergic agonist bronchodilators generally are preferred initially for the symptomatic relief of bronchospasm in patients with asthma. Current guidelines for the management of asthma and many clinicians recommend concomitant anti-inflammatory therapy with orally inhaled corticosteroids as first-line therapy for long-term management of asthma in adults and children whose symptoms are not controlled by intermittent use of a short-acting β2-adrenergic agonist alone. For additional information on the stepped-care approach for drug therapy in asthma,.
Orally inhaled, selective short-acting β2-adrenergic agonists currently are recommended by an expert panel of the National Asthma Education and Prevention Program (NAEPP) for prehospital management of asthma exacerbations (e.g., in emergency medicine facilities and/or ambulances). During prolonged emergency transport, NAEPP recommends that other asthma therapies such as ipratropium bromide and oral corticosteroids also be available for use. In patients with acute exacerbations of asthma, ipratropium generally has been reserved for use as an adjunct to other therapy, usually in combination with a β2-adrenergic agonist bronchodilator. Because of its delayed onset, ipratropium generally should not be used alone for the management of acute bronchospasm, particularly if a prompt response is required. Some clinicians suggest that adjunctive therapy with ipratropium be considered in the emergency department in patients with moderate or severe exacerbations (peak expiratory flow [PEF] 60-80% or less than 60%, respectively, of predicted or personal best) of asthma who fail to respond adequately to β2-adrenergic agonists and corticosteroids. NAEPP recommends adjunctive therapy with ipratropium (via nebulization or a metered-dose inhaler) and oral corticosteroids in patients with severe asthma exacerbations (FEV1 or PEF less than 40% of predicted or personal best) who fail to respond adequately to short-acting, inhaled β2-agonists. In patients with impending respiratory failure in the emergency department, ipratropium in combination with a short-acting β2-adrenergic agonist (via nebulization) and an IV corticosteroid is recommended. In certain children with acute exacerbations of asthma, some evidence suggests that orally inhaled ipratropium (via nebulization) in conjunction with an orally inhaled β2-adrenergic agonist (via nebulization) may be more effective than therapy with the β2-agonist alone; in one study in children with severe acute asthma, children with the most severe bronchospasm (defined as baseline FEV1 not exceeding 30% of predicted) who received via nebulization repeated doses of ipratropium in conjunction with albuterol were less likely to require hospitalization or additional bronchodilator therapy than children receiving albuterol alone. However, ipratropium does not appear to confer additional benefit in children once they have been hospitalized and treated with an intensive regimen including a nebulized β2-agonist and systemic corticosteroids. Based on such data in children, NAEPP recommends discontinuance of ipratropium upon hospitalization for severe asthma exacerbations for patients of all age groups.
The benefit of maintenance therapy with ipratropium in patients with chronic asthma remains to be elucidated, but the drug may be useful as alternative therapy in adults experiencing adverse effects (e.g., tachycardia, arrhythmia, tremor) with a β2-adrenergic agonist. Some experts currently consider orally inhaled anticholinergics to have a limited role or no role in the long-term management of asthma in children because of a lack of data on safety and efficacy.
Orally inhaled ipratropium may be particularly useful for preventing or reversing bronchospasm induced by β2-adrenergic blocking agents (e.g., propranolol) in asthmatic patients; β2-adrenergic bronchodilators generally are ineffective for this indication in such patients.
Prevention of Exercise-Induced Bronchospasm
Although orally inhaled ipratropium bromide has been effective in the prevention of exercise-induced asthma in a limited number of patients, orally inhaled β2-adrenergic agonists are considered first-line agents in the management of this condition.
Orally inhaled ipratropium bromide has produced bronchodilation (i.e., increase in FEV1) in a limited number of patients with cystic fibrosis, but additional studies are needed to determine the clinical usefulness of such therapy in these patients.
Ipratropium also has been used in a limited number of patients to minimize increases in lung resistance following anesthetic induction and tracheal intubation; to protect against bronchoconstriction in patients undergoing fiberoptic bronchoscopy; and to improve pulmonary function in ventilator-dependent patients, including preterm infants. In a few patients with COPD and myasthenia gravis, ipratropium has been used to counteract the bronchoconstriction and the increase in respiratory secretions associated with cholinesterase inhibitor (e.g., pyridostigmine) therapy in these patients.
Ipratropium bromide is used as a 0.03% nasal spray for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children 6 years of age or older. The drug also is used as a 0.06% nasal spray for the symptomatic relief of rhinorrhea associated with the common cold in adults and children 5 years of age or older.