Summary of Safety Profile: The safety experience with Onbrez Breezhaler comprises exposure of up to 1 year at doses 2- to 4-fold the recommended therapeutic doses.
The most common adverse drug reactions at the recommended doses were nasopharyngitis, cough, upper respiratory tract infection and muscle spasms. These were in the vast majority mild or moderate and became less frequent when treatment was continued.
At the recommended doses, the adverse drug reaction profile of Onbrez Breezhaler in patients with chronic obstructive pulmonary disease (COPD) shows clinically insignificant systemic effects of β2-adrenergic stimulation. Mean heart rate changes were <1 beat/min and tachycardia was infrequent and reported at a similar rate as under placebo treatment. Relevant prolongations of QTcF were not detectable in comparison to placebo. The frequency of notable QTcF-intervals [ie, >450 ms (males) and >470 ms (females)] and reports of hypokalaemia were similar to placebo. The mean of the maximum changes in blood glucose were similar on Onbrez Breezhaler and on placebo.
Description of Population: The Onbrez Breezhaler Phase III clinical development program consisted of 8 key studies and enrolled 5430 patients with a clinical diagnosis of moderate to severe COPD. Safety data from 5 of these studies with treatment durations of 12 weeks or longer were pooled from 2484 patients exposed to indacaterol up to 600 mcg once-daily, of which 957 were on treatment with 150 mcg once-daily and 853 on treatment with 300 mcg once-daily. Approximately 41% of patients had severe COPD. The mean age of patients was 63 years, with 47% of patients aged 65 years or older and the majority (86%) was Caucasian.
Adverse Drug Reactions From Clinical Trials: Adverse drug reactions in the table are from this pooled COPD safety database, listed according to MedDRA system organ class and sorted in descending order of frequency on indacaterol 150 mcg once-daily. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category using the following convention (CIOMS III) is also provided for each adverse reaction: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000), including isolated reports. (See table.)
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At a higher dose ie, 600 mcg once-daily, the safety profile of Onbrez Breezhaler was overall similar to that of recommended doses. Additional adverse drug reactions were tremor and anaemia. Nasopharyngitis and muscle spasm occurred more frequently than at the recommended doses.
Selected Adverse Drug Reactions: In Phase III clinical studies, health care providers observed during clinic visits that on average of 17-20% patients experienced a sporadic cough that occurred usually within 15 sec following inhalation and typically lasted for 5 sec. This cough experienced post inhalation was generally well tolerated and did not lead to any patient discontinuing from the studies at the recommended doses (cough is a symptom of COPD and overall only 6.6% of patients reported cough as an adverse event). There is no evidence that cough experienced post inhalation is associated with bronchospasm, exacerbations, deteriorations of disease or loss of efficacy.