Aclidiniumside effects

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

Paradoxical bronchospasm

Worsening of narrow-angle glaucoma

Worsening of urinary retention

Immediate hypersensitivity reactions Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough. To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 3-Month and 6-Month Trials TUDORZA PRESSAIR was studied in two 3-month (Trials B and C) and one 6-month (Trial D) placebo-controlled trials in patients with COPD. In these trials, 636 patients were treated with TUDORZA PRESSAIR at the recommended dose of 400 mcg twice daily. The population had a mean age of 64 years (ranging from 40 to 89 years), with 58% males, 94% Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV 1 ) percent predicted of 48%. Patients with unstable cardiac disease, narrow-angle glaucoma, or symptomatic prostatic hypertrophy or bladder outlet obstruction were excluded from these trials. Table 1 shows all adverse reactions that occurred with a frequency of greater than or equal to 1% in the TUDORZA PRESSAIR group in the two 3-month and one 6-month placebo-controlled trials where the rates in the TUDORZA PRESSAIR group exceeded placebo.

Table 1: Adverse Reactions (% Patients) in Placebo-Controlled Clinical Trials Treatment Adverse Reactions TUDORZA PRESSAIR Placebo Preferred Term (N=636) (N=640) n (%) n (%) Headache 42 32 Nasopharyngitis 35 25 Cough 19 14 Diarrhea 17 9 Sinusitis 11 5 Rhinitis 10 8 Toothache 7 5 Fall 7 3 Vomiting 7 3 In addition, among the adverse reactions observed in the clinical trials with an incidence of less than 1% were diabetes mellitus, dry mouth, 1 st degree AV block, osteoarthritis, cardiac failure, and cardio-respiratory arrest. Long-term Safety Trials TUDORZA PRESSAIR was studied in three long-term safety trials, two double blind and one open label, ranging from 40 to 52 weeks in patients with moderate to severe COPD. Two of these trials were extensions of the 3-month trials, and one was a dedicated long-term safety trial. In these trials, 891 patients were treated with TUDORZA PRESSAIR at the recommended dose of 400 mcg twice daily. The demographic and baseline characteristics of the long-term safety trials were similar to those of the placebo-controlled trials. The adverse events reported in the long-term safety trials were similar to those occurring in the placebo-controlled trials of 3 to 6 months. No new safety findings were reported compared to the placebo-controlled trials. Long-Term Trial of up to 3-Years In a long-term safety trial with 3630 moderate to very severe COPD patients with previous major cardiac events or cardiovascular risk factors at baseline, the adverse reactions reported with a frequency ≥2% in the TUDORZA PRESSAIR group in which the exposure-adjusted incidence rate exceeds the placebo group were nausea, back pain, cough, hypertension, sinusitis, constipation, arthralgia, anemia, muscle spasms, cardiac failure congestive, cellulitis, and gastroesophageal reflux disease. No other new adverse reactions were identified.

6.2 Postmarketing

Experience The following adverse reactions have been identified during postapproval use of drug TUDORZA PRESSAIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In postmarketing experience with TUDORZA PRESSAIR, immediate hypersensitivity reactions, including anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching have been reported. Additionally, nausea, dysphonia, blurred vision, urinary retention, tachycardia, and stomatitis have been observed.