Treatment Innovations: New Treatment Options for Asthma-Albuterol sulfate

This First Report Managed Care Treatment In­novations highlights 2 studies; the first looked at safety data of ProAir RespiClick (albuterol sulfate) multidose, dry powder inhaler (MDPI) in patients with persistent asthma, while the second study evaluated the drug’s efficacy and safety in exercise-induced bronchospasm (EIB).^4,5

OVERVIEW

On March 31, 2015, Teva Pharmaceutical Industries Ltd received FDA approval for the first and only breath-actuated, multidose, dry powder, short-acting beta-agonist (SABA) inhaler. ProAir RespiClick (albuterol sulfate) inhalation powder is a beta-2-adrenergic agonist indicated for the treatment or prevention of bronchospasm with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm (EIB) in patients ≥12 years of age.

For treatment of acute episodes of bronchospasm or prevention of symptoms associated with bronchospasm, the recommended dosage is 2 inhalations repeated every 4 to 6 hours. In some patients, 1 inhalation every 4 hours may be sufficient. For prevention of EIB, the recommended dosage is 2 inhalations 15 to 30 minutes before exercise. The rescue inhaler contains 200 actuations with each dose delivering 108 µg of albuterol sul-fate (equivalent to 90 µg of albuterol base).¹

The Food and Drug Administration approval was based on a comprehensive clinical development program consisting of 8 clinical trials evaluating the safety and efficacy of albuterol sulfate in patients ≥12 years of age with asthma and EIB. The results showed that albuterol sulfate was safe and effective with adverse events consistent with those seen with previous albuterol inhalers.²

Asthma is a chronic disease of inflammation of both the large and small airways of the lungs, characterized by symptoms of wheezing and coughing. Asthma prevalence is significant with an estimated 25.9 million Americans suffering from the lung condition.^2,3

 PERSISTENT ASTHMA

To evaluate the safety of albuterol sulfate MDPI in patients ≥12 years old with persistent asthma, Raphael et al⁴ reported on the pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies; the initial 12-week double-blind phase of a 52-week, multi­center, safety study; and safety data from the 40-week, open-label phase of a 52-week study. In each study, eligible patients received placebo MDPI or albuterol sulfate MDPI 180 μg (2 inhalations of 90 μg each) 4 times/day for 12 weeks. In the 40-week, open-label phase of the 52-week safety study, patients received albuterol sulfate MDPI 180 μg (2 inhalations of 90 μg each) as needed.

 During both 12-week studies and the 12-week, double-blind phase of the 52-week study, the research­ers found adverse effects (AEs) were more common with placebo MDPI (50%; n=333) vs albuterol sulfate MDPI (40%; n=321). The most frequent AEs were up­per respiratory tract infection, nasopharyngitis, and headache. In the 40-week, open-label phase, the safety profile of albuterol sulfate MDPI was similar to that observed during the 12-week pooled analysis; the most frequent AEs were nasopharyngitis, sinusitis, and upper respiratory tract infection.

 EXERCISE-INDUCED ASTHMA

In a small study of 38 patients conducted by Os­trom et al,5 albuterol sulfate MDPI demonstrated clinically significant protection from EIB compared with placebo MDPI in patients age 12 to 50 years. The single-dose, randomized, double-blind, placebo-controlled, 2-treatment, 2-sequence, 2-way crossover study randomized patients to treatment sequences of albuterol sulfate MDPI (180 μg [2 inhalations of 90 μg each])/placebo MDPI (n=19) or the reverse sequence (n=19). The primary efficacy endpoint was maximum percentage fall from baseline in FEV1 observed up to 60 minutes post-exercise challenge. The researchers found that the estimated mean percentage fall in FEV₁ was 6.2% in patients treated with albuterol sulfate MDPI vs 22.4% in patient treated with placebo MDPI. No new safety issues were observed with short-term albuterol sulfate MDPI use.⁵

 Safety Notes

Life-threatening paradoxical bronchospasm may occur with albuterol sulfate. If this occurs, imme­diately discontinue albuterol sulfate and treat with an alternative therapy. Albuterol sulfate, like other beta-adrenergic agonists, can produce clinically significant cardiovascular events in some patients. Therefore, use with caution in patients with cardio­vascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

The most common AEs in >1% of patients treated with albuterol sulfate compared with placebo were back pain, pain, gastroenteritis viral, sinus headache, and urinary tract infection.¹

 Albuterol Sulfate Facts

• Albuterol sulfate is the first and only breath-actuated, multidose, dry powder, SABA inhaler approved for the treatment or prevention of bronchospasm with reversible obstructive airway disease and for the prevention of EIB in patients ≥12 years of age.

• Clinical trials found that the beta-2-adrenergic agonist was safe and effective with AEs consistent with those seen with previous albuterol inhalers.

• Albuterol sulfate is marketed by Teva Respiratory, LLC.

 Additional Resource

Prescribing Information for albuterol sulfate: https:// www.myproair.com/respiclick/library/docs/PI.pdf

1. ProAir RespiClick [package insert]. Horsham, PA: Teva Respiratory, LLC; March 2015.

2. Teva announces FDA approval of ProAir RespiClick  [news release]. Jerusalem, Israel. Teva Pharma¬≠ceutical Industries Ltd. www.tevapharm.com/ news/teva_announces_fda_approval_of_pro¬≠air_respiclick_04_15.aspx. Accessed November 11, 2015.

3. Asthma and Allergy Foundation of America website. Asthma facts and figures. www.aafa.org. Accessed No­vember 11, 2015.

4. Raphael G, Taveras H, Iverson H, O‚ÄôBrien C, Miller D. Twelve- and 52-week safety of albuterol multidose dry inhaler in patients with persistent asthma. J Asthma. 2015 Sept 15. [Epub ahead of print].

5. Ostrom NK et al. Novel albuterol multidose dry powder inhaler in patients with exercise-induced bronchoconstriction: A single-dose, double-blind, randomized, 2-way crossover study. Respir Med. 2015;109(11):1410-1415.