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.

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 (17.7)].

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.

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

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.

ATROVENT HFA has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids commonly used in the treatment of chronic obstructive pulmonary disease. With the exception of albuterol, there are no formal studies fully evaluating the interaction effects of ATROVENT HFA and these drugs with respect to safety and effectiveness.

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

The active ingredient in ATROVENT HFA is ipratropium bromide (as the monohydrate). It is an anticholinergic bronchodilator chemically described as 8-azoniabicyclo[3.2.1]octane, 3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-,bromide monohydrate, (3-endo, 8-syn)-: a synthetic quaternary ammonium compound, chemically related to atropine. The structural formula for ipratropium bromide is:

C20H30BrNO3•H2O  ipratropium bromide  Mol. Wt. 430.4

Ipratropium bromide is a white to off-white crystalline substance, freely soluble in water and methanol, sparingly soluble in ethanol, and insoluble in lipophilic solvents such as ether, chloroform, and fluorocarbons.

ATROVENT HFA is a pressurized metered-dose aerosol unit for oral inhalation that contains a solution of ipratropium bromide. The 200 inhalation unit has a net weight of 12.9 grams. After priming, each actuation of the inhaler delivers 21 mcg of ipratropium bromide from the valve in 56 mg of solution and delivers 17 mcg of ipratropium bromide from the mouthpiece. The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between the actuation of the device and inspiration through the delivery system. The excipients are HFA-134a (1,1,1,2-tetrafluoroethane) as propellant, sterile water, dehydrated alcohol, and anhydrous citric acid. This product does not contain chlorofluorocarbons (CFCs) as propellants.

ATROVENT HFA should be primed 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.

Conclusions regarding the efficacy of ATROVENT HFA were derived from two randomized, double-blind, controlled clinical studies. These studies enrolled males and females ages 40 years and older, with a history of COPD, a smoking history of > 10 pack-years, an FEV1 < 65% and an FEV1/FVC < 70%.

One of the studies was a 12-week randomized, double-blind active and placebo controlled study in which 505 of the 507 randomized COPD patients were evaluated for the safety and efficacy of 42 mcg (n=124) and 84 mcg (n=126) ATROVENT HFA in comparison to 42 mcg (n=127) ATROVENT CFC and their respective placebos (HFA n=62, CFC n=66). Data for both placebo HFA and placebo CFC were combined in the evaluation.

Serial FEV1 (shown in Figure 1, below, as means adjusted for center and baseline effects on test day 1 and test day 85 (primary endpoint)) demonstrated that 1 dose (2 inhalations/21 mcg each) of ATROVENT HFA produced significantly greater improvement in pulmonary function than placebo. During the six hours immediately post-dose on day 1, the average hourly improvement in adjusted mean FEV1 was 0.148 liters for ATROVENT HFA (42 mcg) and 0.013 liters for placebo. The mean peak improvement in FEV1, relative to baseline, was 0.295 liters, compared to 0.138 liters for placebo. During the six hours immediately post-dose on day 85, the average hourly improvement in adjusted mean FEV1 was 0.141 liters for ATROVENT HFA (42 mcg) and 0.014 liters for placebo. The mean peak improvement in FEV1, relative to baseline, was 0.295 liters, compared to 0.140 liters for placebo.

ATROVENT HFA (42 mcg) was shown to be clinically comparable to ATROVENT CFC (42 mcg).

Figure 1 Day 1 and Day 85 (Primary Endpoint) Results

In this study, both ATROVENT HFA and ATROVENT CFC formulations were equally effective in patients over 65 years of age and under 65 years of age.

The median time to improvement in pulmonary function (FEV1 increase of 15% or more) was within approximately 15 minutes, reached a peak in 1 to 2 hours, and persisted for 2 to 4 hours in the majority of the patients. Improvements in Forced Vital Capacity (FVC) were also demonstrated.

The other study was a 12-week, randomized, double-blind, active-controlled clinical study in 174 adults with COPD, in which ATROVENT HFA 42 mcg (n=118) was compared to ATROVENT CFC 42 mcg (n=56). Safety and efficacy of HFA and CFC formulations were shown to be comparable.

The bronchodilatory efficacy and comparability of ATROVENT HFA vs ATROVENT CFC were also studied in a one-year open-label safety and efficacy study in 456 COPD patients. The safety and efficacy of HFA and CFC formulations were shown to be comparable.

Product: 50090-0961

NDC: 50090-0961-0 200 AEROSOL, METERED in a CANISTER / 1 in a CARTON

See FDA-Approved Patient Labeling

Appropriate and safe use of ATROVENT HFA includes providing the patient with the information listed below and an understanding of the way it should be administered [see FDA-approved Patient Labeling (17.8)].

Advise patients that 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.

Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA

Licensed from:
Boehringer Ingelheim International GmbH

Copyright 2012 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED

IT1902II122012
10003001/09

INSTRUCTIONS FOR USE

Atrovent® HFA
(ipratropium bromide HFA)
Inhalation Aerosol

Read the Instructions for Use before using your ATROVENT HFA and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.

Use ATROVENT HFA exactly as your healthcare provider tells you to. Do not change your dose or how often you use ATROVENT HFA without talking with your healthcare provider.

Tell your doctor about all the medicines you take. ATROVENT HFA may affect the way some other medicines work and some other medicines may affect the way ATROVENT HFA works.

Important information about using ATROVENT HFA

• You do not have to shake ATROVENT HFA before using it.
  
  
• ATROVENT HFA should be "primed" 2 times before you use the first dose of a new ATROVENT HFA inhaler or when the inhaler has not been used for more than 3 days.
  
  
  • To prime, push the canister against the mouthpiece (See Figure 1), allowing the medicine to spray into the air.
    
  • Do not spray the medicine into your eyes while priming ATROVENT HFA.

Inhaler Description

ATROVENT HFA Inhalation Aerosol (Figure 1) consists of a metal canister containing the medicine and a mouthpiece that releases the medicine from the canister. The mouthpiece includes a clear colorless sleeve, a white plastic portion and a green protective dust cap.

The inhaler comes with a dose indicator you can see through a small window on the plastic mouthpiece (See Figure 1). A new inhaler first shows “200” in the dose indicator window. The dose indicator will show the approximate number of actuations (sprays) of medicine remaining in the inhaler. As you use the inhaler, the dose indicator will typically rotate during every 5 to 7 actuations (sprays) towards the next decreasing number (See Figure 2).

Figure 1

Figure 2

Instructions for Use:

1. Insert the metal canister into the clear end of the mouthpiece (See Figure 1). Make sure the canister is fully and firmly inserted into the mouthpiece.
   
   
   • The ATROVENT HFA canister is to be used only with the ATROVENT HFA mouthpiece.
     
     
   • Do not use the ATROVENT HFA mouthpiece with other inhaled medicines.
     
     
2. Remove the green protective dust cap. If the cap is not on the mouthpiece, make sure there is nothing in the mouthpiece before use. For best results, the canister should be at room temperature before use.
   
   
3. Breathe out (exhale) deeply through your mouth. Hold the inhaler upright (See Figure 3), between your thumb and first 2 fingers. Put the mouthpiece in your mouth and close your lips.
   
   
   • Keep your eyes closed so that no medicine will be sprayed into your eyes. If sprayed into the eyes, ATROVENT HFA can cause blurry vision and other vision abnormalities, eye pain or discomfort, dilated pupils, or narrow-angle glaucoma or worsening of this condition. If any combination of these symptoms develops, you should consult your physician immediately.
     
     

     Figure 3

4. Breathe in (inhale) slowly through your mouth and at the same time spray the ATROVENT HFA into your mouth.
   
   
   • To spray ATROVENT HFA firmly press the canister against the mouthpiece 1 time (See Figure 4). Keep breathing in deeply.
     
     

     Figure 4

5. Hold your breath for ten seconds and then take the mouthpiece out of your mouth and breathe out slowly (See Figure 5).
   
   

   Figure 5

6. Wait at least 15 seconds and repeat steps 3 to 5 again.
   
   
7. Replace the green protective dust cap after use.
   
   
8. Keep the mouthpiece clean. At least once a week, wash the mouthpiece, shake it to remove excess water and let it air dry all the way (see Mouthpiece Cleaning Instructions).

Mouthpiece Cleaning Instructions:

 

Step A. Remove and set aside the canister and dust cap from the mouthpiece (See Figure 1).

Step B. Wash the mouthpiece through the top and bottom with warm running water for at least 30 seconds (See Figure 6). Do not use anything other than water to wash the mouthpiece.

Figure 6

Step C. Dry the mouthpiece by shaking off the excess water and allow it to air dry all the way.

Step D. When the mouthpiece is dry, replace the canister. Make sure the canister is fully and firmly inserted into the mouthpiece.

Step E. Replace the green protective dust cap.

If little or no medicine comes out of the mouthpiece, wash the mouthpiece as described in Steps A to E under the "Mouthpiece Cleaning Instructions".

9.

When to get a new ATROVENT HFA inhaler.

There are approximately 40 actuations (sprays) left when the dose indicator displays “40,” where the background changes from green to red (See Figure 7a). This is when you need to refill your prescription or ask your doctor if you need another prescription for ATROVENT HFA inhalation aerosol.

The background color will be all red when the indicator approaches 20. The indicator will stop moving at “0”. Discard the inhaler once the dose indicator displays “0” (See Figure 7b). Even though the canister may not be empty, you cannot be sure of the amount of medicine in each actuation (spray) once the dose indicator displays “0”.

Figure 7a

Figure 7b

This product does not contain any chlorofluorocarbon (CFC) propellants.

The contents of ATROVENT HFA are under pressure. Do not puncture the canister. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw the container into a fire or incinerator.

Keep ATROVENT HFA and all medicines out of the reach of children.

Address medical inquiries to: http://us.boehringer-ingelheim.com, (800) 542-6257 or (800) 459-9906 TTY.

Store ATROVENT HFA at Room Temperature [77°F (25°C)]. Short-term exposure to higher or lower temperatures [from 59°F (15°C) to 86°F (30°C)] is acceptable.

Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA

Licensed from:
Boehringer Ingelheim International GmbH

Copyright 2012 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED

IT1902II122012
10003001/09

Revised: August 2012