Levalbuterol outperforms standard albuterol in treating acute asthma. (Better Bronchodilation at 1 Hour).
Marketed by Sepracor Inc. under the brand name Xopenex, levalbuterol contains only the therapeutically active R-isomer of albuterol. All other currently available albuterol bronchodilators are 50/50 racemic mixtures, containing both R- and S-isomers. Much lower doses of the single R-isomer are needed to achieve the same therapeutic effect, and data suggest that the S-isomer may impede the action of the R-isomer, said Dr. Nowak, vice chair of emergency medicine at Henry Ford Hospital and Medical Centers, Detroit.
"If the association between high S levels and resistance to therapy and persistent bronchospasm persists, I'm not sure you can disregard the S-isomer and say that the American public should continue to take it, given what we know I think at some point, the Food and Drug Administration will have to Look at it very closely," he said.
For patients with mild asthma using occasional low albuterol doses, the difference between levalbuterol and the racemic mixture may not be clinically relevant. But for those with significant symptoms who use rescue medications for days at a time--particularly those who show up at the emergency room--the difference may indeed be significant. "Over time, accumulation of the S-isomer could become toxic," Dr. Nowak told this newspaper.
In an open-label, dose-escalation study conducted at two U.S. centers, 92 adults with moderate-severe asthma (20%-55% of predicted forced expiratory volume in 1 second, or [FEV.sub.1] were treated with three nebulized doses of either levalbuterol or racemic albuterol within the first hour, followed by more as needed.
A levalbuterol dose of 1.25 mg produced significantly better bronchodilation at 1 hour following the last dose than did either 2.5 or 5 mg of racemic albuterol ([FEV.sub.1] 2.2 L vs. 1.8 and 1.9 L, respectively). Patients who received 1.25 mg levalbuterol also had a greater percent change in [FEV.sub.1] from baseline (100% vs. 50%-55%). And clinically significant improvement in [FEV.sub.1] (50%) occurred 30-40 minutes faster with levalbuterol.
Only 7% of patients treated with three 1.25-mg doses of levalbuterol in the first hour required more treatment, compared with 43% of those treated with three 2.5-mg doses of the racemic mixture. Higher doses of levalbuterol did not produce significantly better results. "So, 1.25 mg seems like the right dose," said Dr. Nowak, who is on the speakers' bureau for Sepracor.
The sickest patients-those with baseline [FEV.sub.1] 35% or less of predicted value-fared even better with 1.25 mg levalbuterol, with a 145% increase at 1 hour, compared with an increase of 30% with 2.5 mg racemic albuterol and 70% with 5 mg of the racemic mixture.
All of these patients had been using large doses of racemic albuterol prior to coming in to the emergency room. Pre-dose blood levels of the S-isomer were associated with smaller improvements in [FEV.sub.1] with levalbuterol doses of 3.75 mg or 5 mg of racemic albuterol.
"It may be that if you have a lot of S on board, you won't see an improvement until it's gone," Dr. Nowak remarked.
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|Author:||Tucker, Miriam E.|
|Publication:||Internal Medicine News|
|Article Type:||Product/Service Evaluation|
|Date:||Jan 1, 2003|
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