Atrovent HFA

ATROVENT HFA- ipratropium bromide aerosol, metered
Boehringer Ingelheim Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

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

2 DOSAGE AND ADMINISTRATION

The usual starting dose 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 [see Patient Counseling Information (17) ].

3 DOSAGE FORMS AND STRENGTHS

ATROVENT HFA is an inhalation aerosol supplied in a pressurized stainless steel canister as a metered-dose inhaler with a white mouthpiece that has a clear, colorless sleeve and a green protective cap. Each pressurized metered-dose aerosol unit for oral inhalation contains a 12.9 g solution of ipratropium bromide that provides sufficient medication for 200 actuations. After priming, each actuation of the inhaler delivers 21 mcg of ipratropium bromide (as the monohydrate) from the valve and delivers 17 mcg of ipratropium bromide from the mouthpiece.

4 CONTRAINDICATIONS

ATROVENT HFA is contraindicated in the following conditions [see Warnings and Precautions (5.2) ].

• Hypersensitivity to ipratropium bromide or other ATROVENT HFA components
• Hypersensitivity to atropine or any of its derivatives

5 WARNINGS AND PRECAUTIONS

5.1 Use for Maintenance Treatment Only

ATROVENT HFA is a bronchodilator for the maintenance treatment of bronchospasm associated with COPD and is not indicated for the initial treatment of acute episodes of bronchospasm where rescue therapy is required for rapid response.

5.2 Hypersensitivity Reactions, Including Anaphylaxis

Hypersensitivity reactions including urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema may occur after the administration of ATROVENT HFA. In clinical trials and postmarketing experience with ipratropium-containing products, hypersensitivity reactions such as skin rash, pruritus, angioedema of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported [see Adverse Reactions (6.1, 6.2)]. If such a reaction occurs, therapy with ATROVENT HFA should be stopped at once and alternative treatment should be considered [see Contraindications (4) ].

5.3 Paradoxical Bronchospasm

ATROVENT HFA can produce paradoxical bronchospasm that can be life threatening. If this occurs, treatment with ATROVENT HFA should be stopped and other treatments considered.

5.4 Ocular Effects

ATROVENT HFA is an anticholinergic and its use may increase intraocular pressure. This may result in precipitation or worsening of narrow-angle glaucoma. Therefore, ATROVENT HFA should be used with caution in patients with narrow-angle glaucoma [see Drug Interactions (7.1) ].

Patients should avoid spraying ATROVENT HFA into their eyes. If a patient sprays ATROVENT HFA into their eyes, they may cause eye pain or discomfort, temporary blurring of vision, mydriasis, visual halos or colored images in association with red eyes from conjunctival and corneal congestion. Advise patients to consult their physician immediately if any of these symptoms develop while using ATROVENT HFA Inhalation Aerosol.

5.5 Urinary Retention

ATROVENT HFA is an anticholinergic and may cause urinary retention. Therefore caution is advised when administering ATROVENT HFA Inhalation Aerosol to patients with prostatic hyperplasia, or bladder-neck obstruction [see Drug Interactions (7.1) ].

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.

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 1010 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) ].