Ipratropiumside effects

Adverse reaction information concerning ipratropium bromide inhalation solution is derived from 12-week active-controlled clinical trials. Additional information is derived from foreign post-marketing experience and the published literature. All adverse events, regardless of drug relationship, reported by three percent or more patients in the 12-week controlled clinical trials appear in the table below. Additional adverse reactions reported in less than three percent of the patients treated with ipratropium bromide include tachycardia, palpitations, eye pain, urinary retention, urinary tract infection and urticaria. Cases of precipitation or worsening of narrow-angle glaucoma and acute eye pain have been reported. Lower respiratory adverse reactions (bronchitis, dyspnea and bronchospasm) were the most common events leading to discontinuation of ipratropium bromide therapy in the 12-week trials. Headache, mouth dryness and aggravation of COPD symptoms are more common when the total daily dose of ipratropium bromide equals or exceeds 2,000 mcg. Allergic-type reactions such as skin rash, angioedema of tongue, lips and face, urticaria, laryngospasm and anaphylactic reaction have been reported. Many of the patients had a history of allergies to other drugs and/or foods. All Adverse Events, from a Double-blind, Parallel, 12-week Study of Patients with COPD* PERCENT OF PATIENTS Ipratropium Bromide (500 mcg t.i.d) n=219 Metaproterenol (15 mg t.i.d) n=212 Ipratropium Bromide/ Metaproterenol (500 mcg t.i.d/15 mg t.i.d) n=108 Albuterol (2.5 mg t.i.d) n=205 Ipratropium Bromide/ Albuterol (500 mcg t.i.d/ 2.5 mg t.i.d) n=100 Body as a Whole-General Disorders Headache 6.4 5.2 6.5 6.3 9.0 Pain 4.1 3.3 0.9 2.9 5.0 Influenza-like symptoms 3.7 4.7 6.5 0.5 1.0 Back Pain 3.2 1.9 1.9 2.4 0.0 Chest Pain 3.2 4.2 5.6 2.0

1.0 Cardiovascular

Disorders Hypertension/ hypertension Aggravated 0.9 1.9 0.9 1.5

4.0 Central &

Peripheral Nervous System Dizziness 2.3 3.3 1.9 3.9 4.0 Insomnia 0.9 0.5 4.6 1.0 1.0 Tremor 0.9 7.1 8.3 1.0 0.0 Nervousness 0.5 4.7 6.5 1.0

1.0 Gastrointestinal

System Disorders Mouth Dryness 3.2 0.0 1.9 2.0 3.0 Nausea 4.1 3.8 1.9 2.9 2.0 Constipation 0.9 0.0 3.7 1.0

1.0 Musculo-skeletal

System Disorders Arthritis 0.9 1.4 0.9 0.5

3.0 Respiratory

System Disorders (Lower) Coughing 4.6 8.0 6.5 5.4 6.0 Dyspnea 9.6 13.2 16.7 12.7 9.0 Bronchitis 14.6 24.5 15.7 16.6 20.0 Bronchospasm 2.3 2.8 4.6 5.4 5.0 Sputum Increased 1.4 1.4 4.6 3.4

0.0 Respiratory

Disorder 0.0 6.1 6.5 2.0

4.0 Respiratory

System Disorders (Upper) Upper Respiratory Tract Infection 13.2 11.3 9.3 12.2 16.0 Pharyngitis 3.7 4.2 5.6 2.9 4.0 Rhinitis 2.3 4.2 1.9 2.4 0.0 Sinusitis 2.3 2.8 0.9 5.4 4.0 *All adverse events, regardless of drug relationship, reported by three percent or more patients in the 12-week controlled clinical trial.