Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

Abstract

Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma.

Safety outcomes of salbutamol: A systematic review and meta‐analysis

“…The incidences of severe AEs varied in different indication subgroups and formulation subgroups (Table 1). Compared with COPD subgroup (pooled incidence: 6%, 95% CI : 3%–9%), 66 the risk of severe AEs in asthma subgroup was slightly lower (pooled incidence: 2%, 95% CI : 1%–3%, I 2 = 59.2%, P = 0.004), 26,33,50,77,81 while inhaled salbutamol subgroup (pooled incidence: 2%, 95% CI : 1%–3%, I 2 = 67.6%, P = 0.004) 26,33,50,66,77,81 was with a lower risk of severe AEs than intravenous subgroup (pooled incidence: 6%, 95% CI : 2%–9%, P = 0.038) 73 . No studies reported severe AEs either in premature labour subgroup or oral subgroup.…”

“…Based on the full‐text review, 93 articles were ruled out for one or more of the following reasons: reviews, duplicated cohorts, commentaries, non‐randomized trials, non‐human trials or without AEs outcomes. Ultimately, 58 RCTs with a total of 12 961 patients were included in this meta‐analysis 24–81 . The selection procedure is depicted in Figure 1.…”

“…Summary of the main characteristics of the included studies was displayed in Table S1. Of the included 58 trials, the number of salbutamol users ranged from 11 to 8393, which were published from 1978 to 2020, 24–81 and 38 (65.5%), seven (12.1%), five (8.6%) and eight (13.8%) focused on asthma, COPD, premature labour and other bronchoconstriction indications, respectively. Inhaled salbutamol was used in 75.9% of trails (44/58), while oral salbutamol was used in seven trails, and intravenous salbutamol was used in the rest seven trails.…”

“…There was a higher risk of treatment discontinuation in COPD subgroup (pooled incidence: 13%, 95% CI: 2%-23%, I 2 = 88.7%) 35,64,66 than asthma subgroup (pooled incidence: 1%, 95% CI: 1%-2%, I 2 = 0%, P < 0.001). 34,39,41,45,50,54,77 There are no significant differences between oral subgroup and inhaled subgroup (P = 0.108, Table 1). No studies reported treatment discontinuations in either premature labour subgroup or intravenous subgroup.…”

Ensuring Access to Albuterol in Schools: From Policy to Implementation. An Official ATS/AANMA/ALA/NASN Policy Statement

“…For example, schools should be allowed to use albuterol in respiratory emergencies, even when a child lacks a documented asthma diagnosis. Albuterol is a safe drug to administer to any child in respiratory distress ( 35 – 38 ). To obtain stock medication for schools/districts, pharmacy dispensing law(s) should also be addressed.…”