Relieving Obstructive Airway Diseases-Clinical Review and Use of Levosalbutamol-Beclomethasone Combination

Indian Risk Factors for Obstructive Airways Diseases - Difficult to Modify: Reportedly, approximately 38 million people are living with asthma in India. (3) The incidence of asthma is reportedly higher in poorer states compared to richer states, the greater prevalence in northern states of the country compared to north-eastern states; and a trend towards higher incidence in the extreme age groups of life. The burden is highest among those living in households using solid fuels like firewood and kerosene. One-third of the cases could be eliminated by minimizing the use of any solid fuels. Asthma has a significant impact on the emotional well-being of Indian children. (4) Such factors increase the burden of obstructive pulmonary airway illnesses and raise the need for effective maintenance therapies

Scientific Rationale for Levosalbutamol Beclomethasone Combination in the Management of Obstructive Airway Ailments

Short-acting beta2-agonists (SABAs) are rapid onset bronchodilators, selective for the β2-receptor, which provide prompt symptomatic relief. Inhaled corticosteroids (ICS) are used as maintenance treatment for asthma, are effective in reducing airway inflammation, improving airway hyperresponsiveness, and reducing asthma exacerbation risk. As per scientific evidence, an ICS containing reliever medication is superior to SABA as a reliever alone, (5) thus could have the potential to reduce the risk of severe asthma exacerbations

Levosalbutamol Beclomethasone Combination in the Treatment of Obstructive Airway Diseases – Clinical Evidence Review

Levosalbutamol Benefits in Pediatric Population: Berger WE et al, published a study to evaluate the efficacy and safety of levosalbutamol metered-dose inhaler (MDI) among the pediatric population. A multicentred, randomized, double-blind, four-week study, including children (n=173) aged 4-11 years were enrolled. The intervention arms included QID levosalbutamol 90 μg, racemic albuterol 180 μg, and placebo (2:1:1 ). Serial spirometry was performed at baseline, week 2, and week 4 (end of study). The primary endpoint was the double-blind average peak percent (%) change in FEV1 from visit pre-dose. Secondary endpoints included the area under the FEV1 percent change from the pre-dose curve and peak%-predicted FEV1. The results of the study demonstrated that Levosalbutamol significantly improved the least square mean peak percent change in FEV1 compared with placebo (levosalbutamol 25.6% ± 1.3% [p < 0.001]; racemic albuterol 21.8% ± 1.8%; placebo 16.8% ± 1.9%). Results for levosalbutamol were similar for the other spirometry endpoints (p<0.05 vs. placebo). No levosalbutamol-treated patients had a peak percent change in FEV1 < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The rate of discontinuation of treatment was lowest in the levosalbutamol group ( 1.3%) versus 2.6% for racemic albuterol, and 8.6% for placebo. The study inferred that levosalbutamol administered via MDI significantly improved airway function in asthmatic children with a tolerable safety profile in this patient population. (6)

Efficacy of Levosalbutamol in COPD patients: Donohue JF et al, aimed to evaluate the efficacy and safety of nebulized levosalbutamol in adults with chronic obstructive pulmonary disease (COPD). A qualitative, multicentre, randomized, double-blind, parallel design study was designed. Two hundred and nine COPD patients were randomized to receive levosalbutamol, racemic albuterol 2.5 mg, or placebo (control group) thrice daily for 6 weeks. Serial spirometry was completed in-clinic after study drug alone at baseline, week 2, and week 6; or in combination group with ipratropium bromide 0.5 mg at week 4. The endpoints were averaged FEV1 AUC(0–8 hrs), rescue medication use, safety parameters, and COPD exacerbations. The results demonstrated that COPD exacerbations occurred in all groups but were reported to be lowest in the levosalbutamol group. It was concluded that levosalbutamol treatment in subjects with COPD was generally well tolerated, produced significant bronchodilation compared with the control group, and improved clinical control of COPD as evidenced by greater reductions in rescue medication use with levosalbutamol treatment.(7)

Long-term safety study of levosalbutamol inhaler: Hamilos DL et al, aimed to examine the long-term safety of levosalbutamol administered via metered-dose inhaler (MDI) in patients with stable asthma. The study summarised that in patients (n=496) aged > 12 years with mild to moderate asthma and mean forced expiratory volume in 1 second(FEV1) 68.3% of predicted, treatment with Levosalbutamol HFA MDI (90 mcg; 2 actuation of 45 mcg) for 52 weeks with four times daily dosing, was well tolerated without any deterioration in the lung function detected during the study period. (8)

Levosalbutamol As Effective as its combination with Ipratropium in the Treatment of Severe Acute Asthma With Better Tolerance Profile: Cydulka RK et al, conducted a prospective, double-blind, randomized, controlled study involving 141 adults, presenting to two emergency medicine departments with acute severe asthma exacerbation. Patients were treated using a standardized pathway with levosalbutamol plus ipratropium or levosalbutamol alone. Primary outcomes were changes from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at 30 minutes and 60 minutes after treatment. Secondary outcomes included hospitalization and relapse rates. The results of this study demonstrated that there was no significant difference in the percent improvement of predicted FEV1 between the two groups at 30 minutes. No difference was noted in hospitalization rates between the treatment groups. The post-doc analysis revealed that patients receiving ipratropium in addition to levosalbutamol were 1.5 times more likely to experience side effects like palpitations than patients treated with levosalbutamol alone. More side effects were experienced among patients receiving levosalbutamol plus ipratropium combination. The study pointed out that levosalbutamol alone had comparable efficacy in alleviating obstruction, attenuating the need for hospitalization, and reported better tolerance compared to levosalbutamol plus ipratropium combination. (9)

Levosalbutamol in the Prevention of Exercise-Induced Bronchospasm: Pearlman DS, et al, aimed to assess the ability of levosalbutamol 90 μg (two actuations of 45 μg) administered via metered-dose inhaler (MDI) to protect against Exercise-induced bronchospasm (EIB) among mild to moderate asthmatic patients. A randomized, double-blind, placebo-controlled, two-way cross-over study was conducted; which enrolled mild to moderate adult asthmatic patients, with prior history of EIB, ≥70% baseline predicted forced expiratory volume in 1 second (FEV1), using single-blind placebo MDI. Levosalbutamol or placebo was self-administered 30 minutes before exercise. Spirometry was performed pre-dose, 20 minutes post-dose/pre-exercise, and 5,10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV1 from baseline (post-dose/pre-exercise). The results demonstrated that Levosalbutamol had a significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo [Least square mean (LS) mean ± SE; −4.8% ± 2.8% versus −22.5% ± 2.8%, respectively]. For levosalbutamol, 93.3% patients had <20% decrease in post-exercise FEV1 compared with 53.3% for placebo (p = 0.0143). It was thus concluded, that levosalbutamol MDI administered before exercise is significantly effective than placebo in protecting against EIB after an exercise challenge and could be considered effective for protecting adults with asthma from exercise-induced bronchospasm.(10)

Benefits of Levosalbutamol Beclomethasone Combination

Levosalbutamol could offer prompt symptomatic relief and Beclomethasone could help in attenuating airway inflammation and airway hyperresponsiveness and diminishing obstructive airways' bronchospastic exacerbation risk. (5) In addition, levosalbutamol-based therapies may possess several additional clinical advantages. Levosalbutamol is clinically proven to improve airway function among the asthmatic pediatric population (6) and it could reduce bronchospastic exacerbations and the need for rescue medications among COPD patients. (7) Levosalbutamol could also prevent exercise-induced bronchospasms among asthmatic patients. (10) Importantly, it is reportedly effective and well-tolerated for use over a long period of 52 weeks (8)

Summary

The burden of obstructive airway illnesses is huge in Indian practice settings (3) which could have detrimental clinical implications. (4) With difficult-to-modify household and environmental factors like pollution, decisions regarding selecting appropriate maintenance therapy may need to be prudent. Short-acting beta2-agonists (SABAs) and Inhaled corticosteroids (ICS) based combination treatment may be useful in selected clinical scenarios pertaining to reversible obstructive airway diseases. (6 ,7, 9 ,10)

References