UTIBRON NEOHALER SIDE EFFECTS

SIDE EFFECTS

The following clinically significant adverse reactions are described in greater detail in other sections:

• Serious Asthma-Related Events – Hospitalizations, Intubations, Death
• Paradoxical Bronchospasm
• Hypersensitivity Reactions, including Anaphylaxis
• Cardiovascular Effects
• Worsening of Narrow-Angle Glaucoma
• Worsening of Urinary Retention

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.

The UTIBRON NEOHALER safety database included 2654 subjects with COPD in two 12-week lung function trials and one 52-week long-term safety study. A total of 712 subjects received treatment with UTIBRON NEOHALER 27.5 mcg/15.6 mcg twice daily. The safety data described below are based on the two 12-week trials and the one 52-week trial.

12-Week Trial

The incidence of adverse reactions associated with UTIBRON NEOHALER in Table 1 is based on two 12-week, placebo-controlled trials (Trials 1 and 2; N = 1,001 and N = 1,042, respectively). Of the 2040 subjects, 63% were male and 91% were Caucasian. They had a mean age of 63 years and an average smoking history of 47 pack-years, with 52% identified as current smokers. At screening, the mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV₁) was55%(range: 29% to 79%), the mean post-bronchodilator FEV₁/forced vitalcapacity(FVC) ratio was 50% (range: 19% to 71%), and the mean percent reversibility was 23% (range: 0% to 144%).

The most common adverse reaction (incidence greater than or equal to 2% and higher than placebo) was nasopharyngitis and hypertension.

The proportion of patients who discontinued treatment due to adverse reactions was 2.95% for the UTIBRON NEOHALER treated patients and 4.13% for placebo-treated patients.

Subjects received 1 dose twice daily of the following: UTIBRON NEOHALER 27.5 mcg/15.6 mcg, indacaterol 27.5 mcg, glycopyrrolate 15.6 mcg, or placebo.

Table 1: Adverse Reactions with UTIBRON NEOHALER (greater than or equal to 1% incidence and higher than placebo) in COPD Patients

Other adverse reactions occurring more frequently with UTIBRON NEOHALER than with placebo, but with an incidence of less than 1% include dyspepsia, gastroenteritis, chest pain, fatigue, peripheral edema, rash/pruritus, insomnia, dizziness, bladder obstruction/urinary retention, atrial fibrillation, palpitations, tachycardia.

52-Week Trial

In a long-term safety trial, 614 subjects were treated for up to 52 weeks with indacaterol/glycopyrrolate 27.5 mcg/15.6 mcg twice daily, indacaterol/glycopyrrolate 27.5/31.2 mcg twice daily or indacaterol 75 mcg once daily. The demographic and baseline characteristics of the long-term safety trial were similar to those of the placebo-controlled efficacy trials described above. The adverse reactions reported in the long-term safety trial were consistent with those observed in the placebo-controlled trials of 12 weeks. Additional adverse reactions that occurred with a frequency greater than or equal to 2% in the group receiving indacaterol/glycopyrrolate 27.5 mcg/15.6 mcg twice daily that exceeded the frequency of indacaterol 75 mcg once daily in this trial were upper and lower respiratory tract infection, pneumonia, diarrhea, headache, gastroesophageal reflux disease, hyperglycemia, rhinitis.

Postmarketing Experience

The following additional adverse reactions of angioedema and dysphonia have been identified during worldwide post-approval use of indacaterol/glycopyrrolate at higher than the recommended dose. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

SRC: NLM .