asone propionate/salmeterol inhalation powder) or ICS (fluticasone propionateinhalation powder). In this trial 27/3,107 (0.9%) of patients treated with ICS/LABA and 21/3,101 (0.7%) of patients treated with ICS experienced a serious asthma-related event. There were noasthma-related deaths or intubations. ICS/LABA did not show a significantly increased risk of aserious asthma-related event compared to ICS based on the prespecified risk margin (2.7), withan estimated hazard ratio of time to first event of 1.29 (95% CI: 0.73, 2.27).
Salmeterol Multicenter Asthma Research Trial (SMART)
A 28-week, placebo-controlled, U.S. trial that compared the safety of salmeterol with placebo,each added to usual asthma therapy, showed an increase in asthma-related deaths in subjectsreceiving salmeterol (13/13,176 in subjects treated with salmeterol versus 3/13,179 in subjectstreated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]). Use of background ICS was notrequired in SMART. The increased risk of asthma-related death is considered a class effect ofLABA monotherapy.
5.2 Deterioration of Disease and Acute Episodes
AirDuo Digihaler should not be initiated in patients during rapidly deteriorating or potentiallylife-threatening episodes of asthma. AirDuo Digihaler has not been studied in subjects withacutely deteriorating asthma. The initiation of AirDuo Digihaler in this setting is not appropriate.
Serious acute respiratory events, including fatalities, have been reported when salmeterol, acomponent of AirDuo Digihaler, has been initiated in patients with significantly worsening oracutely deteriorating asthma. In most cases, these have occurred in patients with severe asthma(e.g., patients with a history of corticosteroid dependence, low pulmonary function, intubation,mechanical ventilation, frequent hospitalizations, previous life-threatening acute asthma
exacerbations) and in some patients with acutely deteriorating asthma (e.g., patients withsignificantly increasing symptoms; increasing need for inhaled, short-acting beta2-agonists;decreasing response to usual medications; increasing need for systemic corticosteroids; recentemergency room visits; deteriorating lung function). However, these events have occurred in afew patients with less severe asthma as well. It was not possible from these reports to determinewhether salmeterol contributed to these events.
When beginning treatment with AirDuo Digihaler, patients who have been taking oral or inhaled,short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed todiscontinue the regular use of these drugs.
5.3 Excessive Use of AirDuo Digihaler and Use with Other Long-ActingBeta2-AgonistsAirDuo Digihaler should not be used more often than recommended, at higher doses thanrecommended, or in conjunction with other medicines containing LABA, as an overdose mayresult. Clinically significant cardiovascular effects and fatalities have been reported inassociation with excessive use of inhaled sympathomimetic drugs. Patients using AirDuoDigihaler should not use another medicine containing a LABA (e.g., salmeterol, formoterolfumarate, arformoterol tartrate, indacaterol) for any reason.
5.4 Local Effects of Inhaled Corticosteroids
In clinical trials, the development of localized infections of the mouth and pharynx with Candidaalbicans has occurred in subjects treated with fluticasone propionate and |
