Question

• A pediatric patient with asthma experiences undesired side effects when treated with racemic albuterol nebulizations.  In the pediatric population with reactive airways disease, will treatment with levalbuterol (Xopenex) decrease side effects, improve treatment, or decrease costs?

Clinical Bottom Lines

1. Levalbuterol is more potent than racemic albuterol.¹  Levalbuterol 1.25mg had the greatest effect and side effects.
2. Levalbuterol 0.63 and racemic albuterol 2.5 (1.25mg R-isomer) are similar in effect and side effects.
3. Levalbuterol costs six times as much in this university setting compared to racemic albuterol.  Levalbuterol 0.63mg and 1.25mg cost $1.55/unit;  racemic albuterol 2.5mg costs $0.26/unit.²
4. Levalbuterol is only delivered by nebulization.
5. Currently, "Xopenex appears to have no clinically significant advantage over racemic albuterol." ³

Summary of Key Evidence

1. 43 children ages 2-11 were randomized into a crossed-over, double-blind study.¹  Inclusion criteria were asthma history 6+ months, FEV₁ 50-80% predicted with <10% variability in FEV₁.  Had 12% reversibility with 2.5mg albuterol NMT.
2. Had pre- and post-treatment visits.  Four visits involved treatment with either racemic albuterol 1.25mg or 2.5mg, levalbuterol 0.16, 0.31, 0.63, or 1.25mg, or placebo.  Serial PFTs, as well as enantiomer levels, were obtained  Side effects were evaluated.
3. 28 children wereincluded in efficacy analysis, 33 in the safety analysis.  Assessed for efficacy by using the change in FEV₁, %change in FEV₁, and area under the curve (AUC).  All treatment groups were significantly more effective than placebo, except that racemic albuterol 1.25mg was not better than placebo in AUC.  Levalbuterol 1.25mg was the most potent in terms of efficacy, but the effect was clinically small.  Levalbuterol 0.63mg and 0.31mg were comparable with racemic albuterol 2.5mg.
4. All side effects were mild to moderate with all medications.  Asthma exacerbations, headaches, increase in blood sugar and heart rate, decrease in potassium were adverse effects.  Levalbuterol 1.25mg had the most and greatest side effects; levalbuterol 0.63mg and racemic albuterol 2.5mg have comparable side effects. 

Additional Comments

• The use of this medication amkes biological sense.  Racemic albuterol consists of equal amounts of R- and S- isomers.  R-albuterol is the active agent, interacting with Beta-2 receptors in airways.  It is believed that the non-specific interactions with Beta-1 receptors (seen with albuterol) cause some side effects.
• Another study examined 362 patients 12 years or older.  In this study, children were treated with treatments TID for 1 month with levalbuterol or albuterol and found little differences in effects or side effects.⁴
• The studies^1,4 were sponsored by manufacturer of Xopenex (Sepracor, Inc.)
• Other studies need to be performed, including looking at children with co-morbidity, those receiving continuous or frequent treatments, with exacerbations, or cotreatment with other medications (i.e. prophylaxis).  Further study on the role of S-albuterol is also needed.

Citation

1. Gawchick SM, Sacca CL, Noonan M, Reasner DS, DeGraw SS.  The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients.  Journal of Allergy and Clinical Immunology, 1999; 103(4):615-21.
2. Personal communication, UM Pharmacy, 1/2000.
3. Levalbuterol for Asthma.  The Medical Letter, 1999; 41:51-3.
4. Nelson HS, Bensch G, Pleskow WW, DiSantostefano R, DeGraw S, Reasner DS, Rollins TE, RobinPD.  Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma.  Journal of Allergy and Clincial Immunology, 1999; 102(6):943-52.

CAT Author: Karl Nicles, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: January 24, 2000