bananaface said:
The S-isomer is active - just not as a B2-agonist.
Aight..that's a fair statement since it's binds to muscarinic receptor in vitro and in animals. But clinically, it's inert. Despite some of the Sepracor sponsored studies.
Albuterol and levalbuterol share many of the same characteristics and actions. There has been discrepancy in the literature surrounding levalbuterols superiority to albuterol. Many claims have been made which indicate that S-albuterol, the inactive enantiomer in albuterol may not be inactive, but have some detrimental properties. Some of these are that S-albuterol works in opposition to R-albuterol, that S-albuterol leads to the tolerance effect seen with the bronchodilator, that it increases airway hyperresponsiveness, and that it causes the systemic effects of racemic albuterol.6
To date, there has been no study demonstrating a significant difference between levalbuterol and albuterol. Because of the lack of data to support superiority of levalbuterol it is difficult to justify the additional expense of levalbuterol.
Cockcroft et al7 found that tolerance developed after six days to groups treated with R-albuterol or racemic albuterol. However patients did not develop tolerance after being treated with S-albuterol or to placebo treatment. Doing this, they proved that S-albuterol was not responsible for the development of tolerance.
Randomized trials have not demonstrated that S-albuterol causes hyperresponsiveness in the lung tissue of asthmatic patients.
Three studies show that the systemic effects of racemic albuterol are due to the R- enantiomer, and not the S-enantiomer.
Two studies8,9 both sponsored by Sepracor, the manufacturer of Xopenex®, claim that levalbuterol led to fewer hospitalizations and decreased cost to the hospital. However, the Carl study did not predefine hospital admission criteria and the two groups of patients that were admitted had no difference in clinical presentation at admission, end of ED stay, and duration of hospitalization.
Clinical Trials
Trial Regimens Methods Results Comments
Carl, et al Levalbuterol Nebs 1.25mg q20min or albuterol 2.5mg q20min in the ER 547 enrollments from 478 children (85% black, 67% male) with acute asthmaExcluded: first episode, no current treatment, pregnant, hypersensitive to alb, CF, cyanosis, uncorrected congenital heart disease, chronic obstructive lung diseaseLev n=278Alb n=269Pts <6 y/o face mask nebPts >=6y/o mouthpiece nebReceive nebs q20 min until met discharge criteria or max of 6 tx in 2 hrs (admit the pt at that point)Given oral prednisone after 1st treatment if not meet DC criteriaSupplemental O2 given prnOption for intensification of therapy if requiredPrimary outcome measure: hospital admission rate 547 episodes in 477 patients. PEP 36% admin rate for levalbuterol vs. 45% for albuterol. There was no difference other endpoints. Outcome Alb Leva P Value
Hosp Admin 45 36 0.02
LOS Hrs 2.2 2.3 0.25
Tx/patient 4.1 3.7 0.08
Resp Rate 35.6 37.0 0.26
NNT for primary endpoint: 10.6Pts who used >=2 aerosols in previous 2 hours had 40% higher hospital admission rate (RR=1.39, 95% CI=1.13-1.72, p=0.02)Pts who used >3 aerosols in previous 2 hours had more admissions (RR=1.34, 95% CI=1.09-1.51, p=0.004) More patients in the levalbuterol group were treated with cromolyn & inhaled Sterioid.The Admission criteria was not well defined and based on the ER MD who was not part of the study. Because data on pulmonary function was noted therefore reasons for the difference in admission rate is unclear.
Debapriya et al Levalb 1.25mg Alb 2.5mg Alb 2.5mg + Ipr 0.5mg or placebo. Randomized DB, Placebo CCT, comparing albuterol, levalbuterol, ipratropium and placebo in patients with COPD. N=30PEP : FEV1 FVC, pulse, O2 sat. Positive Bronchodilator Response
Time (hr) 0.5 1
Alb 43% 47%
Alb/Ipr 43% 53%
Levalb 40% 40%
Placebo 13% 13%
None of the bronchodilators increase FEV1 past 4 hrs. None of the other PEP show significant differences. The duration of action of albuterol and levalbuterol was shorter than described in other studies.
Truitt T, et al.9Retrospective chart reviewSupported by Sepracor Albuterol 2.5 mg q 4h (Alb) vsLevalbuterol 1.25 mg q 8h (Lev) 231 charts reviewedTwo six-month periods with these two drugs on formulary Charts were searched for ICD codes for asthma, COPDExcluded: concomitant cognitive disturbances, cancerAlb n=125 (90 pts COPD, 35 pts asthma)Lev n=106 (87 pts COPD, 19 pts asthma)PEP: total number of neb treatments requiredSEP: Primary endpoint reached30.8 treatments alb vs 19.0 treatments lev p<0.001 Additional outcome measures: changes in PFTs, duration of hospitalization, disposition following hospitalization, pharmacy utilization costs, resource utilization costsBy design (treatment protocol) the pts treated with alb automatically had twice as many nebs scheduled than the pts on levUsed inflated basis of AWP to calculate cost of drug
Adverse Effects (Safety Data)
Despite the fact that these two agents are selective for the ß2 receptor, they still cause tachycardia to some degree. None of the ß2 agonists are completely selective, and furthermore, with increasing doses of any agent, the selectivity for the ß2 receptor decreases.1
Adults
levalbuterol1.25 mg racemic albuterol2.5 mg
Tachycardia 2.7 2.7
Dizziness 2.7 0
Nervousness 9.6 8.1
Anxiety 2.7 0
Tremor 6.8 2.7
Dyspepsia 2.7 1.4
Rhinitis 2.7 6.8
Increased cough 4.1 2.7
Children
levalbuterol0.63 mg racemic albuterol1.25 mg
Asthma 9.0 6.3
Headache 11.9 9.4
Myalgia 1.5 1.6
Pharyngitis 10.4 0
Rhinitis 10.4 3.1
Drug Mean Changes from Baseline2
Heart Rate (bpm) Glucose (mg/dL)
Adults
Levalbuterol 1.25 mg 6.9 10.3
Albuterol (racemic) 2.5 mg 5.7 8.2
Significant No no
Children
Levalbuterol 0.63 mg 6.7 5.2
Albuterol (racemic) 1.25 mg 6.4 8.0
Significant No no
- sorry! I should have thought of this particular one of yours 
