Efficacy Similar for Levalbuterol, Racemic Albuterol in Acute Asthma

Abstract

Source: Qureshi F, Zaritsky A, Welch C, et al. Clinical efficacy of racemic albuterol versus levalbuterol for the treatment of acute pediatric asthma. Ann Emerg Med. 2005;46:29–36. Albuterol is the mainstay of therapy for patients with acute asthma. The drug typically comes in a racemic form, with equal parts of the R- and S-enantiomer. Levalbuterol, marketed as Xopenex (Sepracor Inc., Marlborough, Mass.), consists of only the R-isomer. It has been suggested that the R-enantiomer of albuterol is responsible for the drug’s bronchodilating effects1 and that the S-enantiomer is responsible for adverse effects, including tachycardia, tremors, and nervousness.2 While some studies have concluded that levalbuterol is more effective than racemic albuterol with fewer side effects, the data are inconclusive.3,4 Researchers from the Children’s Hospital of the King’s Daughters, Eastern Virginia Medical School in Norfolk, Va., conducted a prospective, double-blind, randomized, controlled efficacy study to compare levalbuterol with racemic albuterol in patients ages 2 to 14 years with acute asthma who presented to the pediatric emergency department (ED). Patients were enrolled if they had moderate or severe symptoms documented by a previously validated clinical asthma score greater than 8 or a forced expiratory volume in 1 second (FEV1) less than 70% of predicted (for those able to perform spirometry).5 After randomization, patients weighing less than 25 kg were given unit doses of 1.25 mg levalbuterol or 2.5 mg racemic albuterol, and patients heavier than or equal to 25 kg were given 2.5 mg levalbuterol or 5 mg racemic albuterol. Patients received 3 nebulized treatments at 20-minute intervals, with subsequent treatments every 30 to 60 minutes at the discretion of the attending ED physician. All patients also received oral corticosteroid therapy with the second treatment. Ipratropium bromide therapy was not given until after the third nebulized treatment. Main outcome measures included changes from the baseline clinical asthma score and FEV1, measured after the first, third, and fifth nebulizer treatments. Secondary outcomes included number of nebulized treatments until disposition, rate of hospitalization, number of adverse events, and changes over time in pulse rate, respiratory rate, and oxygen saturation. The authors calculated that to have a 90% chance of detecting a 10% difference in FEV1 between study groups, 61 children would be required in each group. (For a discussion of power calculations, see accompanying box, “Weighing the Evidence.”)There were 68 patients randomized to the racemic albuterol group and 71 to the levalbuterol group. The initial median asthma score in both groups was 10, and the median FEV1 percent predicted was 25% in the levalbuterol group and 27% in the racemic albuterol group. The groups did not differ significantly in improvement in clinical asthma score or change in FEV1 percent predicted after the first, third, or fifth treatments. No analyses were done on FEV1 differences after the fifth treatment because of the small number of subjects. In addition, there were no differences in median number of nebulizations (3 in each group), percent of patients hospitalized (11% in levalbuterol group vs. 13% in racemic albuterol group), or changes over time in pulse, respiratory rate, or pulse oximetry.Dr. Paul has disclosed no financial relationships relevant to this commentary. However, there is discussion of an unapproved/investigative use of a commercial product/device. Levalbuterol is FDA-approved for children ages 6 years and older. This study includes children ages 2 to 14 years.Many practitioners have questioned whether the much higher cost of levalbuterol is justified by any clinical advantage over the much less expensive albuterol.6 At my institution, the cost for albuterol is 32 cents for a 2.5-mg dose compared to $2.24 for a 1.25-mg dose of levalbuterol (7 times more expensive per treatment). This study of pediatric patients with moderate to severe acute asthma provides further evidence that levalbuterol has similar efficacy and offers no improvement in adverse effects when compared to albuterol. If the S-enantiomer were a cause of increased adverse effects or decreased efficacy when using racemic albuterol, then a treatment protocol such as the one used in this study, where several doses of the drug are given in a short period of time, would be more likely to uncover those effects. However, this study found no decrease in adverse effects or improvement in primary outcome measures among patients who received levalbuterol compared to those who received racemic albuterol. Unless severe adverse effects develop with the use of racemic albuterol, levalbuterol may not be worth the extra cost.