Atrovent Hfa Drug Information

Inhalation Aerosol is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. ATROVENT HFA is an anticholinergic indicated for the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema

The usual starting dosage of ATROVENT HFA is two inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. ATROVENT HFA is a solution aerosol that does not require shaking.

However, as with any other metered-dose inhaler, some coordination is required between actuating the canister and inhaling the medication. Patients should "prime" or actuate ATROVENT HFA before using for the first time by releasing 2 test sprays into the air away from the face. In cases where the inhaler has not been used for more than 3 days, prime the inhaler again by releasing 2 test sprays into the air away from the face.

Patients should avoid spraying ATROVENT HFA into their eyes. Each inhaler provides sufficient medication for 200 actuations. The inhaler should be discarded after the labeled number of actuations has been used.

The amount of medication in each actuation cannot be assured after this point, even though the canister is not completely empty. Patients should be instructed on the proper use of their inhaler. For oral inhalation only Two inhalations four times a day, not to exceed 12 inhalations in 24 hours

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.

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.

Anticholinergic Agents

There is potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of ATROVENT HFA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

Pregnancy Risk Summary Ipratropium is negligibly absorbed systemically following oral inhalation; therefore, maternal use is not expected to result in fetal exposure to the drug. There is limited experience with ipratropium bromide use in pregnant women. Published literature, including cohort studies, case control studies and case series, over several decades have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Based on animal reproduction studies, no evidence of structural alterations was observed when ipratropium bromide was administered to pregnant mice, rats and rabbits during organogenesis at doses up to approximately 200, 40,000, and 10,000 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In animal reproduction studies, oral and inhalation administration of ipratropium bromide to pregnant mice, rats and rabbits during the period of organogenesis did not show evidence of fetal structural alterations. The ipratropium bromide dose in oral studies in mice, rats, and rabbits was up to approximately 200, 40,000, and 10,000 times, respectively, the MRHDID in adults (on a mg/m 2 basis at maternal doses of 10, 1,000, and 125 mg/kg/day, respectively). The ipratropium bromide dose in inhalation studies in rats and rabbits was up to approximately 60 and 140 times, respectively, the MRHDID in adults (on a mg/m 2 basis at maternal doses of 1.5 and 1.8 mg/kg/day, respectively). Embryotoxicity was observed as increased resorption in rats at oral doses approximately 3,600 times the MRHDID in adults (on a mg/m 2 basis at maternal doses of 90 mg/kg/day and above). This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration.

Pediatric Use Safety and effectiveness in the pediatric population have not been established.

is contraindicated in the following conditions. Hypersensitivity to ipratropium bromide or other ATROVENT HFA components Hypersensitivity to atropine or any of its derivatives Hypersensitivity to ipratropium bromide or other ATROVENT HFA components Hypersensitivity to atropine or any of its derivatives

Acute overdose by inhalation is unlikely since ipratropium bromide is not well absorbed systemically after inhalation or oral administration.