Atrovent HFA

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Hypersensitivity Reactions, Including Anaphylaxis [ see Contraindications (4) and Warnings and Precautions (5.2) ] Paradoxical Bronchospasm [ see Warnings and Precautions (5.3) ] Ocular Effects [ see Warnings and Precautions (5.4) ] Urinary Retention [ see Warnings and Precautions (5.5) ] 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 patients. Most common adverse reactions (>5% incidence in the 12-week placebo-controlled trials) were bronchitis, COPD exacerbation, dyspnea, and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience The adverse reaction information concerning ATROVENT HFA is derived from two 12-week, double-blind, parallel-group studies and one 1-year open-label, parallel group study. These studies compared ATROVENT HFA Inhalation Aerosol, ATROVENT CFC Inhalation Aerosol, and placebo (in one study only) in 1,010 COPD patients. The following table lists the incidence of adverse reactions that occurred at a rate of greater than or equal to 3% in any ipratropium bromide group and greater than placebo in the 12-week study. The frequency of corresponding reactions in the 1-year open label study is included for comparison. TABLE 1 Adverse Reactions (% Patients) in ATROVENT HFA Clinical Trials Placebo-controlled 12-week Study 244.1405 and Active-controlled 12-week Study 244.1408 Active-controlled 1-year Study 244.2453 ATROVENT HFA (N=243) % ATROVENT CFC (N=183) % Placebo (N=128) % ATROVENT HFA (N=305) % ATROVENT CFC (N=151) % BODY AS A WHOLE - GENERAL DISORDERS Back pain 2 3 2 7 3 Headache 6 9 8 7 5 Influenza-like symptoms 4 2 2 8 5 CENTRAL & PERIPHERAL NERVOUS SYSTEM DISORDERS Dizziness 3 3 2 3 1 GASTROINTESTINAL SYSTEM DISORDERS Dyspepsia 1 3 1 5 3 Mouth dry 4 2 2 2 3 Nausea 4 1 2 4 4 RESPIRATORY SYSTEM DISORDERS Bronchitis 10 11 6 23 19 COPD exacerbation 8 14 13 23 23 Dyspnea 8 8 4 7 4 Sinusitis 1 4 3 11 14 URINARY SYSTEM DISORDERS Urinary tract infection 2 3 1 10 8 Cough, rhinitis, and upper respiratory infection occurred in greater than or equal to 3% of patients in either ipratropium treatment group but not greater than placebo in the 12-week study. In the one open-label controlled study in 456 COPD patients, the overall incidence of adverse events was also similar between ATROVENT HFA and ATROVENT CFC formulations. Overall, in the above mentioned studies, 9.3% of the patients taking 42 mcg ATROVENT HFA and 8.7% of the patients taking 42 mcg ATROVENT CFC reported at least one adverse event that was considered by the investigator to be related to the study drug. The most common drug-related adverse events were dry mouth (1.6% of ATROVENT HFA and 0.9% of ATROVENT CFC patients), and taste perversion (bitter taste) (0.9% of ATROVENT HFA and 0.3% of ATROVENT CFC patients). As an anticholinergic drug, cases of precipitation or worsening of narrow-angle glaucoma, glaucoma, halo vision, conjunctival hyperemia, corneal edema, mydriasis, acute eye pain, dry throat, hypotension, palpitations, urinary retention, tachycardia, constipation, bronchospasm, including paradoxical bronchospasm have been reported with the use of ATROVENT. Additional adverse reactions identified for ATROVENT seen in clinical trials include throat irritation, stomatitis, mouth edema, and vision blurred. Allergic-type reactions such as skin rash, pruritus, angioedema including that of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported [ see Warnings and Precautions (5.2) ]. 6.2 Postmarketing Experience In a 5-year, placebo-controlled trial, hospitalizations for supraventricular tachycardia and/or atrial fibrillation occurred with an incidence rate of 0.5% in COPD patients receiving ATROVENT CFC. In addition to the adverse reactions reported in the controlled clinical trials, adverse reactions have been identified during post-approval use of ATROVENT. 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. Allergic-type reactions such as skin rash, angioedema including that of tongue, lips and face, urticaria (including giant urticaria), laryngospasm, and anaphylactic reactions have been reported, with positive rechallenge in some cases. Additionally, urinary retention, mydriasis, gastrointestinal distress (diarrhea, nausea, vomiting), cough and bronchospasm, including paradoxical bronchospasm, hypersensitivity reactions, intraocular pressure increased, accommodation disorder, heart rate increased, pharyngeal edema, and gastrointestinal motility disorders have been reported during the postmarketing period with use of ATROVENT.