Onbrez Breezhaler Adverse Reactions

Summary of the safety profile: The safety experience with Onbrez Breezhaler comprises exposure of up to one year at doses two- to four-fold the recommended therapeutic doses.
The most common adverse drug reactions at the recommended doses were nasopharyngitis, upper respiratory tract infection, cough, headache, 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 COPD shows clinically insignificant systemic effects of beta₂-adrenergic stimulation. Mean heart rate changes were less than one beat per minute, and tachycardia was infrequent and reported at a similar rate as under placebo treatment. Relevant prolongations of QT_cF were not detectable in comparison to placebo. The frequency of notable QT_cF intervals [i.e., >450 ms (males) and >470 ms (females)] and reports of hypokalemia 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 16 key studies and enrolled over 9,000 patients with a clinical diagnosis of moderate to severe COPD. Safety data from 11 of these studies with treatment durations of 12 weeks or longer were pooled from 4,764 patients exposed to indacaterol up to 600 microgram once-daily, of which 2,611 were on treatment with 150 microgram once-daily and 1,157 on treatment with 300 microgram once-daily. Approximately 41% of patients had severe COPD. The mean age of patients was 64 years, with 48% of patients aged 65 years or older, and the majority (80%) was Caucasian.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions in Table as follows are from this pooled COPD safety database, listed according to MedDRA system organ class and sorted in descending order of frequency on indacaterol 150 microgram 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 (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000). (See table.)

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At a higher, non-recommended dose, i.e., 600 microgram once-daily, the safety profile of Onbrez Breezhaler was overall similar to that of recommended doses. An additional adverse drug reaction was tremor. Nasopharyngitis, muscle spasm, headache and peripheral oedema occurred more frequently than at the recommended doses.
Description of selected adverse drug reactions: In Phase III clinical studies, healthcare providers observed during clinic visits that on average 17-20% of patients experienced a sporadic cough that occurred usually within 15 seconds following inhalation and typically lasted for 5 seconds. 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 up to 8.2% 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.