Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles.To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma.We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006.All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist.In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information.Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16).Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

The Food and Drug Administration (FDA) is confirming the effective date of April 23, 2007, for the direct final rule that appeared in the Federal Register of December 7, 2006 (71 FR 70870). The direct final rule amends the regulation to remove beclomethasone, dexamethasone, fluticasone, bitolterol, salmeterol, ergotamine tartrate, and ipratropium bromide, used in oral pressurized metered-dose inhalers, from the list of essential uses of ozone-depleting substances. None of these products is currently being marketed. This document confirms the effective date of the direct final rule.

To assess the utilization of leukotriene modifiers (LM) relative to national guidelines and to investigate possible emergency room utilization differences for LMs as monotherapy versus inhaled corticosteroid (ICS) monotherapy or combination ICS and LM therapy.The utilization of leukotriene modifiers (montelukast sodium, zafirlukast, and zileuton), concurrent inhaled steroids (beclomethasone, budesonide, flunisolide, fluticasone, and triamcinolone), beta-agonists (albuterol, bitolterol, formoterol, isoetharine, levalbuterol, metaproterenol, pirbuterol, salmeterol, and terbutaline) and low-sedating antihistamines ([LSAs] cetirizine, desloratadine, fexofenadine, and loratadine) were assessed from the drug claims database of a large health insurer for dates of service for the 12-month period from September 1, 2001, through August 31, 2002. New-start LM patients were identified as having no previous LM drug claim within a 180-day look-back period from the first date of fill for the LM. Claims were stratified into age cohorts of.under 16 years. and.16 years and older. Emergency room (ER) claims for patients utilizing LMs, ICSs, and patients on both LM and ICS were retrieved for analysis from the medical claims database for the same 12-month study period.More than 89% of new LM starts had no history of an ICS in the claims database. Overall, 61% of all (new and existing) LM patients did not have a claim for an ICS in their drug claims profile during the study period. An estimated 25% of LM utilization was not for asthma. No differences in ER utilization were found between ICS users and LM users; however, the ER utilization rate (0.090 ER visits per patient per year) was lower with combination therapy compared with monotherapy with ICS (0.110 ER visits per patient per year, P = 0.001) or LM (0.119 emergency room visits per patient per year, P<0.001).The majority of LM use in this health plan was initial monotherapy, contrary to national treatment guidelines for asthma. At the time of the study, the apparent off-label use of LM for allergic rhinitis was significant for this health plan.

Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles.To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of asthma.Randomised, controlled trials (RCTs) were identified using the Cochrane Airways Group register. The register was searched using the following terms: asthma and theophylline and long acting beta-agonist or formoterol or foradile or eformoterol or salmeterol or bambuterol or bitolterol. Date of last search was April 2003. Titles and abstracts were then screened to identify potentially relevant studies. The bibliography of each RCT was searched for additional RCTs. Authors of identified RCTs were contacted for other relevant published and unpublished studies.All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist.Potentially relevant trials, identified by screening titles and/or abstracts, were obtained. Two reviewers independently assessed full text versions of these trials to decide whether the trial should be included in the review, and assessed its methodological quality. Where there was disagreement between reviewers, this was resolved by consensus, or reference to a third party. Data were extracted by two independent reviewers. Inter-rater reliability was assessed by simple agreement. Study authors were contacted to clarify randomisation methods, provide missing data, verify the data extracted and identify unpublished studies. Relevant pharmaceutical manufacturers were also contacted.Six trials originally met the inclusion criteria. Five used salmeterol and one, bitolterol. In an updated version of the review, six more trials were included. Four trials used salmeterol and two used formoterol. They were of varying quality. Salmeterol improved FEV1 significantly more than theophylline in five studies and salmeterol use was associated with significantly more symptom free nights in all the studies comparing these agents. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Subjects taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI: 0.30 to 0.63), Risk Difference -0.11 (95%CI: -0.16 to -0.07), NNT 9 (6, 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95%Confidence Intervals 0.29, 0.86), Risk Difference -0.07(95% CI -0.12, -0.02), NNT 14(8, 50) and gastrointestinal adverse events (Relative Risk 0.30; 95%Confidence Intervals 0.17, 0.55), Risk Difference -0.11(-0.16, -0.06), NNT 9(6, 16).Long-acting beta-2 agonists are at least as effective than theophylline in reducing asthma symptoms including night waking and improving lung function. Fewer adverse events occurred in subjects using long-acting beta-2 agonists(salmeterol and formoterol) as compared to theophylline.

Theophylline and long acting beta2-agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles.To assess the comparative efficacy, safety and side-effects of long-acting beta-agonists and theophylline in the maintenance treatment of asthma.Randomised, controlled trials (RCTs) were identified using the Cochrane Airways Group register. The register was searched using the following terms: asthma and theophylline and long acting beta-agonist or formoterol or foradile or eformoterol or salmeterol or bambuterol or bitolterol. Titles and abstracts were then screened to identify potentially relevant studies. The bibliography of each RCT was searched for additional RCTs. Authors of identified RCTs were contacted for other relevant published and unpublished studies.All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-agonist.Potentially relevant trials, identified by screening titles and/or abstracts, were obtained. Two reviewers independently assessed full text versions of these trials to decided whether the trial should be included in the review, and assessed its methodological quality. Where there was disagreement between reviewers, this was resolved by consensus, or reference to a third party. Data were extracted by two independent reviewers. Inter-rater reliability was assessed by simple agreement. Study authors were contacted to clarify randomisation methods, provide missing data, verify the data extracted and identify unpublished studies. Relevant pharmaceutical manufacturers were also contacted.Six trials met the inclusion criteria. Five used salmeterol and one, biltoterol. They were of varying quality. There was a trend for salmeterol to improve FEV1 more than theophylline in three studies and salmeterol use was associated with more symptom free nights. Bitolterol, used in only one study, was reported to be less effective than theophylline. Subjects taking salmeterol experienced fewer adverse events than those using theophylline (Relative Risk 0.38; 95%Confidence Intervals 0.25, 0.57). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.51; 95%Confidence Intervals 0.30, 0.88) and gastrointestinal adverse events (Relative Risk 0.32; 95%Confidence Intervals 0.17, 0.59).Salmeterol may be more effective than theophylline in reducing asthma symptoms including night waking and improving lung function. More adverse events occurred in subjects using theophylline when compared to salmeterol.

There have been numerous studies in asthmatic adults demonstrating the efficacy and safety of bitolterol mesylate metered-dose inhaler; however, only one additional study has examined bitolterol metered-dose inhaler in pediatric asthma.To establish the safety and effectiveness of bitolterol mesylate metered-dose inhaler at one, two, and three inhalations in pediatric asthmatic patients 4 to 12 years of age.A multicenter, double-blind, randomized, crossover, placebo-controlled, dose-ranging study. Forty-six patients were evaluated in three centers. Patients were stratified by age, 4 to 6, 7 to 9, 10 to 12 years at each center. One, two, or three inhalations were administered along with an additional double-blind, randomized, placebo dose. Bronchodilation was defined as a 15% or greater increase in FEV1 over baseline. Onset, maximum improvement, and duration of action were obtained for each patient. Serial pulse rate, blood pressure, and respiratory rate determinations were obtained for each patient.Onset within five minutes occurred in 56.6% to 71% of patients, depending on the dose. Mean maximum improvement, which was dose dependent, overall ranged from 28.2% to 40.3% with a peak response in 66.7 to 69.8 minutes. In direct relationship of magnitude with regard to dose of bitolterol was observed, (P < .001). A significant correlation, r = .732, in response between bronchodilation and baseline FEV1 was observed (P < .001). Median duration of action ranged from three to four hours in responding patients across all doses. Up to 31% of patients had durations greater than eight hours after three inhalations. Adverse effects were reported in five of 46 patients for all doses with mild transient tremor occurring in two patients, 4.3%. Also, there was little effect on pulse rate, 2.2%.Bitolterol is an effective bronchodilator with durations of activity up to eight hours and minimal adverse effects in children.

Metered-dose inhalers (MDIs) may contain as much as 38% ethanol. We evaluated the effects of ethanol-containing MDIs on breath alcohol testing.Prospective, single-blind, crossover, controlled study.Three healthy male volunteers 29 to 36 years old.We studied three brands: Tornalate, (38% ethanol), Bronkometer, (30% ethanol), and Alupent, (0% ethanol). The effects of each MDI on breath and blood ethanol measurements were evaluated separately. Two puffs of each brand of MDI were administered. Breath ethanol measurements were obtained at baseline and .25, .5, 1, 2, 3, 5, and 10 minutes after MDI use. Blood ethanol measurements were obtained at baseline and 1 and 10 minutes after MDI use.Overall, Tornalate had the highest breath ethanol readings, with a mean ethanol level of 189 mg/dL recorded just after MDI use. Breath ethanol levels subsequently decreased rapidly over time. Mean breath ethanol concentrations were lower after the use of Bronkometer and undetectable after the use of Alupent. Blood ethanol levels were undetectable at all times tested.MDIs may cause elevations of breath alcohol above the legal criteria for intoxication. These effects are transient and may be prevented by a 10-minute interval between the use of an MDI and breath alcohol testing.

Patients with reversible bronchospasm benefit from the use of inhaled beta-adrenergic agents. In this retrospective study of 24 older patients with a variety of conditions associated with reversible bronchospasm--asthma, asthma with emphysema, chronic bronchitis, and asthmatic bronchitis--symptomatic improvement was noted after treatment with inhaled bitolterol mesylate. Symptoms resolved or improved after 1 month in 93.8% (15/16) of patients using a metered-dose inhaler and in 75% (6/8) of those using a hand-held nebulizer. Sixteen additional patients were randomly selected to undergo pulmonary function tests after receiving two to three puffs of bitolterol from a metered-dose inhaler. FEV1 improved by 10.9%, FVC by 12.1%, and FEF25%-75% by 34.4% after administration of bitolterol. No adverse events were noted in any patients in either group. The results of this retrospective study suggest that bitolterol is an effective and safe treatment in patients with conditions associated with reversible bronchospasm.

This open-label, placebo-controlled study was undertaken to assess the safety and effectiveness of bitolterol mesylate in pediatric asthma patients. Bitolterol mesylate was administered in increasing doses of 0.5 to 3.5 mg by continuous-flow nebulization on separate days to children 4 to 12 years of age. Pulmonary function tests and vital signs were measured before and for up to eight hours after each treatment. Bronchodilation was defined as a > or = 15% increase in FEV1 over baseline. Onset, magnitude, and duration of bronchodilation all showed general dose-related improvements. Onset of bronchodilation occurred within five minutes in 66% to 82% of all treatments. The mean maximum percent increase in FEV1 ranged from 35% to 52% for all doses. Median durations of bronchodilation in responding patients ranged from four and one tenth to more than eight hours. Bitolterol was well-tolerated with all adverse effects being mild to moderate in severity and transient in nature. Although the incidence of cough, increased pulse rate, and tremor were relatively low, they did increase slightly with the 2.5- and 3.5-mg doses. No significant clinical laboratory or electrocardiographic findings were noted. We conclude that doses of 1.0 and 1.5 mg bitolterol mesylate administered by continuous-flow nebulization are safe, effective, and well-tolerated for the treatment of asthma in pediatric patients.