Here's some info on Xopenex from last year:
Fewer Side Effects Seen With Levalbuterol Versus Racemic Albuterol In Asthmatics
By Marilynn Larkin
CHICAGO, Apr 27 (Reuters) - Use of nebulized levalbuterol results in bronchodilation equivalent to that of racemic albuterol at lower doses and with fewer side effects, Dr. Harold Nelson of the National Jewish Medical and Research Center, Denver, Colorado, reported in a poster session today.
Racemic albuterol, the medication most commonly used to treat asthma, is composed of the isomers (R)-albuterol and (S)-albuterol, notes Dr. Nelson. (R)-albuterol is the active isomer. Recent evidence suggests (S)-albuterol has no benefit and may contribute to some of the adverse effects of racemic albuterol.
The multicenter study compared two doses of levalbuterol with 2 doses of racemic albuterol given by nebulization 3 times daily over a 4-week period in a Phase III, randomized, double-blind, parallel-group study in 328 asthmatic patients.
"The trial was real life as opposed to methacholine challenges, and repetitive dosing is also real life, so that aspect is important," Dr. Nelson told Reuters Health. "Most studies that have suggested problems with beta agonists have been associated with multiple dosing."
In the study, participants were randomly assigned to receive one of the following nebulization treatments 3 times daily for 4 weeks: 0.63 mg levalbuterol, 1.25 mg levalbuterol, 1.25 racemic albuterol, 2.5 mg racemic albuterol, or placebo. Improvement in FEV1 was comparable for the 0.63 mg dose of levalbuterol and the racemic albuterol dose of 2.5 mg, and levalbuterol was associated with "...fewer side effects and a less marked effect on heart rate, serum potassium, and glucose," according to a meeting abstract.
"For any given amount of the (R)-albuterol [levalbuterol], you got greater bronchodilatation compared with the racemic form. That says that what else is in the racemic form must be doing something undesirable--in some way counteracting the bronchodilating effect of (R)-albuterol," Dr. Nelson says.
What is more, he notes, "...with repetitive dosing, after 4 weeks, when people came in to have their 8-hour bronchodilator study done, and had therefore held off on medication overnight, morning FEV1 was significantly lower in the group that had been receiving racemic albuterol compared with either (R)-albuterol or placebo." This suggests "...an effect of (S)-albuterol on the level of pulmonary function that is deleterious," and may possibly occur only with repeated dosing.
This is worrisome, says Dr. Nelson, because "...asthma is a disease of the night, where the normal circadian pattern of pulmonary function is that it's lowest at 4 a.m. So if you happen to be taking something that cause pulmonary function to be lower at that time, it's the worst time to have it happen, since it's already lower, anyway. So it's not a good idea, perhaps, to take racemic albuterol 3 times daily because it has the potential to make asthma worse at the very time that you don't want it to be worse."
More studies are needed to see whether these findings for nebulized albuterol are similar for albuterol delivered via an MDI, says Dr. Nelson.
And here's the abstract of the recent JACI article referred to in the CC:
Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma
Harold S. Nelson, MDa
George Bensch, MDb
Warren W. Pleskow, MDc
Rachael DiSantostefano, MSd
Sidney DeGraw, MPhile
David S. Reasner, PhDe
Thomas E. Rollins, MBAe
Paul D. Rubin, MDe
Denver, Colo, Stockton and Encinitas, Calif, Wilmington, NC, and Marlborough, Mass
Abstract
Background: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental.
Objective: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma.
Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks.
Results: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and -adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids.
Conclusion: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
AUC: Area under the curve
ECG: Electrocardiogram
MDI: Metered-dose inhaler
Publishing and Reprint Information TOP
From athe National Jewish Medical and Research Center, Denver; bAllergy, Immunology & Asthma Group, Inc, Stockton; c317 North El Camino Real, Encinitas; dPPD Pharmaco Inc, Wilmington; and eSepracor Inc, Marlborough.
Presented in part at the annual meeting of the American Thoracic Society, Chicago, Ill, April 1998.
Supported by a grant from Sepracor Inc, Marlborough, Mass.
Received for publication June 3, 1998.
Revised Aug 24, 1998.
Accepted for publication Aug 27, 1998.
Reprint requests: Harold S. Nelson, MD, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206.
Copyright © 1998 by Mosby, Inc.
0091-6749/98 $5.00 + 0 1/1/94588 |
