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Annals of Allergy, Asthma & Immunology... Jun 2003To review the rationale supporting the use of levalbuterol [(R)-albuterol] for the treatment of pediatric and adult asthma. (Review)
Review
LEARNING OBJECTIVES
To review the rationale supporting the use of levalbuterol [(R)-albuterol] for the treatment of pediatric and adult asthma.
DATA SOURCES
Peer-reviewed articles, selected abstracts from studies presented at recent professional meetings, and the Xopenex [levalbuterol, (R)-albuterol; Sepracor, Marlborough, MA] Summary Basis of Approval and package insert.
STUDY SELECTION
Institutional review board-approved clinical study protocols.
RESULTS
Levalbuterol is a single isomer beta2-agonist that differs from racemic albuterol by elimination of (S)-albuterol. Levalbuterol is an effective bronchodilator whose primary mechanism of action is unimpeded by (S)-albuterol. Thus, when compared with racemic albuterol, clinically comparable bronchodilation can be achieved with doses that substantially lessen beta-mediated side effects. In chronic or acute treatment of asthma, this favorable therapeutic profile cannot apparently be duplicated by increasing or decreasing the dose of racemic albuterol or by the addition of anticholinergic agents such as ipratropium bromide.
CONCLUSIONS
Levalbuterol seems to provide efficacy and safety advantages in pediatric and adult patients suffering from asthma. Its use may afford a cost benefit as well. More clinical studies are required to extend these observations for use in the treatment of other pulmonary diseases in both adults and children and to determine levalbuterol's impact on long-term therapy of respiratory diseases.
Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Humans; United States
PubMed: 12839314
DOI: 10.1016/S1081-1206(10)61859-5 -
The Journal of the American Osteopathic... Jul 2004Effective asthma control requires long-term (anti-inflammatory) controller medications for patients with mild-persistent to severe-persistent disease, and quick-relief... (Review)
Review
Effective asthma control requires long-term (anti-inflammatory) controller medications for patients with mild-persistent to severe-persistent disease, and quick-relief bronchodilator medication for all patients with asthma to control intermittent symptoms of cough, wheeze, and bronchoconstriction, as well as acute exacerbations. For patients with chronic obstructive pulmonary disease, quick-relief and long-acting bronchodilators are primarily used in the maintenance and treatment of associated symptoms, including shortness of breath. For many years, the most widely used bronchodilator has been racemic (R, S)-albuterol, a short-acting beta2-adrenergic agonist, commonly dispensed as an inhaled aerosol or solution. Until the introduction of levalbuterol inhalation solution (Xopenex) in 1999, all marketed forms of albuterol (including Ventolin and Proventil brands) were racemic mixtures composed of a 1:1 ratio of (R)- and (S)-stereoisomers. Administered as a proportionally equivalent nebulized dose, levalbuterol [(R)-albuterol] provides greater bronchodilation than racemic albuterol and, in the appropriate clinical setting, offers the possibility for improving clinical outcomes in patients with asthma and other obstructive airway diseases. Additionally, levalbuterol can be given at lower doses than racemic albuterol to provide comparable bronchodilation, with the potential for reduced beta-mediated adverse effects in adults and children. Only since the past decade has the technology to separate stereoisomers become available, and thus the biologic activities of the albuterol stereoisomers had not been established. Binding studies have demonstrated that (R)-albuterol binds to the beta2-adrenergic receptor with a high affinity, whereas (S)-albuterol binds with 100-fold less affinity than (R)-albuterol. Other evaluations have suggested that (R)-albuterol possesses the bronchodilatory, bronchoprotective, and ciliary-stimulatory properties of racemic albuterol, while (S)-albuterol does not contribute beneficially to the therapeutic effects of the racemate and was originally assumed to be inert. However, preclinical evaluations have shown that (S)-albuterol has effects that work in opposition to (R)-albuterol and may diminish the therapeutic effects of (R)-albuterol.
Topics: Albuterol; Asthma; Bronchodilator Agents; Humans; Molecular Structure; Pulmonary Disease, Chronic Obstructive
PubMed: 15293593
DOI: No ID Found -
Chest Sep 2003
Comparative Study
Topics: Albuterol; Asthma; Bronchodilator Agents; Drug Industry; Humans; Propaganda; Racemases and Epimerases; Retrospective Studies; Treatment Outcome
PubMed: 12970056
DOI: 10.1378/chest.124.3.1175 -
The European Respiratory Journal Nov 1994Dizziness, together with hypotension and faintness, are well-known adverse drug reactions of salbutamol that have been related to its cardiovascular effects. However, we...
Dizziness, together with hypotension and faintness, are well-known adverse drug reactions of salbutamol that have been related to its cardiovascular effects. However, we could find no published reference to vertigo in patients taking salmeterol, in the absence of cardiovascular alterations. We present the case of a woman who experienced four independent episodes of vertigo lasting 36 h each, following four inhalations of salmeterol several months apart. The close temporal relationship between the inhalation of salmeterol and the onset of symptoms, as well as the positive re-exposures, reinforce this alleged association.
Topics: Administration, Inhalation; Aged; Albuterol; Asthma; Bronchodilator Agents; Female; Humans; Salmeterol Xinafoate; Vertigo
PubMed: 7875287
DOI: No ID Found -
Journal of Pharmaceutical and... Mar 2007R-albuterol (levalbuterol) is a drug used for asthma therapy and some formulations of it are in solid dosage forms. The aim of this work was to describe and characterize...
R-albuterol (levalbuterol) is a drug used for asthma therapy and some formulations of it are in solid dosage forms. The aim of this work was to describe and characterize two polymorphic modifications of R-albuterol sulfate by means of typical structure-sensitive analytical techniques such as X-ray powder diffraction, FT-IR spectroscopy, visual and microscopic inspection, and DSC. Substantial differences were observed between the solid-state properties of the crystals, confirming the existence of at least two polymorphic forms for R-albuterol sulfate: Form I and Form II.
Topics: Albuterol; Bronchodilator Agents; Calorimetry, Differential Scanning; Crystallization; Drug Stability; Microscopy; Molecular Structure; Powders; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 17141446
DOI: 10.1016/j.jpba.2006.11.009 -
The Journal of Emergency Medicine Apr 2005
Comparative Study
Topics: Albuterol; Bronchodilator Agents; Humans; Stereoisomerism
PubMed: 15769587
DOI: 10.1016/j.jemermed.2004.12.003 -
The Journal of Allergy and Clinical... Apr 1999Limited dose-response information is available for nebulized beta2 -agonists, especially in young children. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Limited dose-response information is available for nebulized beta2 -agonists, especially in young children.
OBJECTIVE
The purpose of this study was to determine the safety and efficacy of increasing doses of nebulized levalbuterol (Xopenex; the pure R-isomer of racemic albuterol) and racemic albuterol compared with placebo in the treatment of asthma in pediatric patients.
METHODS
In this randomized, double-blind, crossover study, children (aged 3 to 11 years) with asthma (resting FEV1 50% to 80% of predicted normal [Polgar's] values) were treated with either levalbuterol, racemic albuterol, or placebo. Eligible subjects underwent a screening visit followed by 4 treatment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determine enantiomer levels, and safety was evaluated.
RESULTS
Five 3- to 5-year-old patients and twenty-eight 6- to 11-year-old patients completed the study, and a total of 87 doses of levalbuterol were administered. In the 6- to 11-year-old group, all doses of levalbuterol were significantly greater than placebo in peak change and percent peak change in FEV1 and area under the FEV1 versus time curve (P <.05). The FEV1 values over the 8-hour study period were similar for levalbuterol 0.31 and 0.63 mg and racemic albuterol 2.5 mg and were greatest after levalbuterol 1.25 mg. Median plasma levels of R-albuterol depended on dose and were 0.4, 0.7, 1.2, and 1.0 after levalbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic albuterol 2.5 mg, respectively. All patients in the 2.5-mg racemic albuterol arm had measurable plasma levels of S-albuterol, although S-albuterol levels were undetectable in most patients in the levalbuterol arms. In a few patients who received levalbuterol, S-albuterol levels were detected, which was likely because of the use of racemic albuterol as a concomitant medication. All active treatments were well tolerated. beta-Mediated changes in heart rate, potassium, and glucose were dose dependent for all active treatment groups.
CONCLUSION
Levalbuterol caused a significantly greater increase in FEV1 than placebo, and FEV1 values were comparable with or better than those observed with racemic albuterol. beta-Mediated side effects were lower for an equipotent dose of levalbuterol when compared with racemic albuterol. Treatment with levalbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters.
Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Stereoisomerism
PubMed: 10200010
DOI: 10.1016/s0091-6749(99)70233-2 -
The American Journal of Managed Care Jan 2005
Comparative Study
Topics: Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Emergency Service, Hospital; Humans; United States
PubMed: 15697101
DOI: No ID Found -
American Journal of Health-system... May 2006The pathogenesis of asthma and the treatment approach for acute exacerbations are described. The pharmacology, efficacy, safety, and cost of the beta2 agonist,... (Review)
Review
PURPOSE
The pathogenesis of asthma and the treatment approach for acute exacerbations are described. The pharmacology, efficacy, safety, and cost of the beta2 agonist, albuterol, a racemic mixture of equal amounts of R- and S-enantiomers, and levalbuterol, the R-enantiomer, are compared.
SUMMARY
Asthma symptoms are the result of bronchial hyperresponsiveness, bronchospasm, and chronic airway inflammation. Short-acting, inhaled beta2 agonists; oxygen; intravenous fluids; and corticosteroids are the mainstays of treatment for acute exacerbations. The R-enantiomer of albuterol is responsible for bronchodilation. The S-enantiomer exhibits broncho-constricting activity in vitro, which may be mediated by muscarinic receptors and may be opposed by adding the anticholinergic agent ipratropium bromide. Levalbuterol improves pulmonary function to a greater extent than racemic albuterol and reduces the need for costly hospitalizations in patients with acute asthma exacerbations.
CONCLUSION
Levalbuterol is an alternative to racemic albuterol with the potential to improve patient outcomes and reduce costs in the treatment of acute asthma exacerbations.
Topics: Adrenergic beta-Agonists; Albuterol; Asthma; Disease Progression; Evidence-Based Medicine; Humans; Stereoisomerism; Treatment Outcome
PubMed: 16679429
DOI: 10.2146/ajhp060127 -
The Annals of Pharmacotherapy May 2013To our knowledge, no data exist regarding the effect of levalbuterol and racemic albuterol on heart rate in pediatric cardiology patients. (Comparative Study)
Comparative Study
BACKGROUND
To our knowledge, no data exist regarding the effect of levalbuterol and racemic albuterol on heart rate in pediatric cardiology patients.
OBJECTIVE
To compare heart rate change in pediatric cardiology patients receiving levalbuterol and/or racemic albuterol. The secondary objective was to identify characteristics associated with heart rate changes observed with these drugs.
METHODS
A review of electronic medical records at a pediatric academic hospital was conducted to determine the equivalence of heart rate change in patients receiving levalbuterol or racemic albuterol. Patients receiving at least 3 doses of levalbuterol and/or racemic albuterol during the study period were included if they were younger than 18 years and had a diagnosis of congenital heart disease (CHD), cardiomyopathy, or supraventricular tachycardia. Patients were excluded if they received a β-blocker or continuous racemic albuterol or did not have documented pre- and postdose heart rates.
RESULTS
One hundred ninety-two patients were included. One hundred forty-two received racemic albuterol, 40 received levalbuterol, and 10 received both racemic albuterol and levalbuterol. The mean increase in heart rate for patients receiving racemic albuterol and levalbuterol was 6.8 beats/min and 6.2 beats/min, respectively (p = 0.01). In patients with CHD, the racemic albuterol group experienced a mean heart rate increase of 6.6 beats/min compared to 6.3 beats/min in the levalbuterol group (p = 0.01). Equivalence was also determined in patients without surgical intervention and patients receiving concomitant cardiac and respiratory medications. Equivalence was not established in other analyzed subgroups secondary to insufficient sample sizes.
CONCLUSIONS
Racemic albuterol and levalbuterol were associated with increased heart rate in pediatric cardiology patients. This increase was found to be equivalent.
Topics: Adolescent; Albuterol; Bronchoconstriction; Bronchodilator Agents; Cardiovascular Diseases; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Heart Rate; Hospitals, Pediatric; Humans; Infant; Male; Retrospective Studies
PubMed: 23613097
DOI: 10.1345/aph.1S003