Atrovent HFA

Name: Atrovent HFA

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store unused vials of the solution in the foil pack until you are ready to use them. Store the medication at room temperature and away from excess heat and moisture (not in the bathroom). Talk to your pharmacist about the proper disposal of medication that is outdated or no longer needed. Do not puncture the aerosol canister, and do not discard it in an incinerator or fire.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What is ipratropium bromide inhaler, and how does it work (mechanism of action)?

Ipratropium bromide is a bronchodilator that dilates (enlarges) airways (bronchi) in the lungs. It is used in treating, symptoms of asthma, colds, allergies, and chronic obstructive pulmonary disease (COPD) due to emphysema or chronic bronchitis. Ipratropium blocks the effect of acetylcholine on airways (bronchi) and nasal passages. Acetylcholine is a chemical that nerves use to communicate with muscle cells. In asthma and chronic obstructive pulmonary disease, cholinergic nerves going to the lungs cause narrowing of the airways by stimulating muscles surrounding the airways to contract. The "anti-cholinergic" effect of ipratropium blocks the effect of cholinergic nerves, causing the muscles to relax and airways to dilate. Mucus glands in the nose also are controlled by nerves that use acetylcholine to communicate. By blocking acetylcholine, ipratropium helps relieve symptoms of allergies and the common cold by preventing secretion of mucus by mucus glands in the nose. When inhaled, ipratropium travels directly to airways, and very little is absorbed into the body. The FDA approved ipratropium in October 1995.

Warnings

Included as part of the PRECAUTIONS section.

Clinical pharmacology

Mechanism of Action

Ipratropium bromide is an anticholinergic (parasympatholytic) agent which, based on animal studies, appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung. Anticholinergics prevent the increases in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle.

Pharmacodynamics

Cardiovascular effects

At recommended doses, ipratropium bromide does not produce clinically significant changes in pulse rate or blood pressure.

Ocular effects

In studies without a positive control, ipratropium bromide did not alter pupil size, accommodation, or visual acuity.

Mucociliary clearance and respiratory secretions

Controlled clinical studies have demonstrated that ipratropium bromide does not alter either mucociliary clearance or the volume or viscosity of respiratory secretions.

Pharmacokinetics

Following administration by oral inhalation from a metered dose inhaler, the majority of the delivered dose is deposited in the gastrointestinal tract and, to a lesser extent, in the lung, the intended site of action. Ipratropium bromide is a quaternary amine and hence is not readily absorbed into the systemic circulation either from the surface of the lung or from the gastrointestinal tract as confirmed by blood level and renal excretion studies.

The half-life of elimination is about 2 hours after inhalation or intravenous administration. Ipratropium bromide is minimally bound (0 to 9% in vitro) to plasma albumin and α1-acid glycoprotein. It is partially metabolized to inactive ester hydrolysis products. Following intravenous administration, approximately one-half of the dose is excreted unchanged in the urine.

A pharmacokinetic study with 29 chronic obstructive pulmonary disease (COPD) patients (48-79 years of age) demonstrated that mean peak plasma ipratropium concentrations of 59±20 pg/mL were obtained following a single administration of 4 inhalations of ATROVENT HFA (84 mcg). Plasma ipratropium concentrations declined to 24±15 pg/mL by six hours. When these patients were administered 4 inhalations QID (16 inhalations/day=336 mcg) for one week, the mean peak plasma ipratropium concentration increased to 82±39 pg/mL with a trough (6 hour) concentration of 28±12 pg/mL at steady state.

Specific Populations

Geriatric Patients

In the pharmacokinetic study with 29 COPD patients, a subset of 14 patients were > 65 years of age. Mean peak plasma ipratropium concentrations of 56±24 pg/mL were obtained following a single administration of 4 inhalations (21 mcg/puff) of ATROVENT HFA (84 mcg). When these 14 patients were administered 4 inhalations four times a day (16 inhalations/day) for one week, the mean peak plasma ipratropium concentration only increased to 84±50 pg/mL indicating that the pharmacokinetic behavior of ipratropium bromide in the geriatric population is consistent with younger patients.

Renally Impaired Patients

The pharmacokinetics of ATROVENT HFA have not been studied in patients with renal insufficiency.

Hepatically Impaired Patients

The pharmacokinetics of ATROVENT HFA have not been studied in patients with hepatic insufficiency.

Drug-Drug Interaction

No specific pharmacokinetic studies were conducted to evaluate potential drug-drug interactions with other medications.

Clinical Studies

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.

How should I use Atrovent HFA (ipratropium inhalation)?

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Ipratropium will not work fast enough to treat an bronchospasm attack. Use only a fast acting inhalation medicine to treat an bronchospasm attack.

Prime the inhaler device before the first use by pumping 2 test sprays into the air, away from your face. Prime the inhaler if it has not been used for longer than 3 days. Clean the inhaler once a week. Follow the cleaning directions that came with your medicine.

The dose indicator on the inhaler will turn from green to red when there are 40 doses left in the device. Get your prescription refilled before you run out of medicine completely. Always use the new device provided with the medication when you get your prescription filled.

Call your doctor right away if it seems like your medications don't work as well, or if your condition gets worse.

While using ipratropium, your lung function may need to be tested often.

Keep the medicine canister away from open flame or high heat, such as in a car on a hot day. The canister may explode if it gets too hot. Do not puncture or burn an empty inhaler canister.

Store the inhaler device with the cover on, at room temperature away from moisture and heat. Throw away the inhaler canister when the dose indicator reaches 0, even if it feels like there is still medicine in it.

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.

Warnings and precautions

  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.

  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 post marketing 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)].

  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.

  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.

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.

  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)].

For the Consumer

Applies to ipratropium: inhalation aerosol liquid, inhalation aerosol powder, inhalation solution

Along with its needed effects, ipratropium (the active ingredient contained in Atrovent HFA) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ipratropium:

More common
  • Bladder pain
  • bloody or cloudy urine
  • cough producing mucus
  • difficult, burning, or painful urination
  • difficulty with breathing
  • frequent urge to urinate
  • lower back or side pain
  • shortness of breath
  • tightness in the chest
  • wheezing
Less common
  • Body aches or pain
  • chills
  • cough
  • ear congestion
  • fever
  • headache
  • loss of voice
  • runny nose
  • sneezing
  • sore throat
  • unusual tiredness or weakness
Rare
  • Constipation (continuing) or lower abdominal pain or bloating
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • severe eye pain
  • skin rash or hives
  • swelling of the face, lips, or eyelids
Incidence not known
  • Blindness
  • blurred vision
  • confusion
  • decrease in the frequency of urination
  • decrease in the urine volume
  • decreased vision
  • difficulty in passing urine (dribbling)
  • difficulty with swallowing
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • hives or welts
  • itching
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • nausea or vomiting
  • noisy breathing
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • redness of the skin
  • redness of the white part of the eyes or inside of the eyelids
  • sweating
  • tearing

Some side effects of ipratropium may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Back pain
  • dryness of the mouth
  • unpleasant taste
Less common or rare
  • Acid or sour stomach
  • belching
  • burning eyes
  • diarrhea
  • general feeling of discomfort or illness
  • heartburn
  • indigestion
  • joint pain
  • loss of appetite
  • muscle aches and pains
  • nervousness
  • pain or tenderness around the eyes and cheekbones
  • shivering
  • stomach discomfort, upset, or pain
  • trembling
  • trouble sleeping

Atrovent HFA May Interact with Other Medications

Atrovent HFA can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well. 

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Medications that might interact with this drug

Antihistamines

Taking these drugs together will increase your risk for side effects from Atrovent HFA. These include blurry vision, dry mouth, problems urinating, constipation, and confusion.

These drugs include:

  • diphenhydramine
  • hydroxyzine
Depression medications

Taking these drugs with certain antidepressants will increase your risk for side effects from Atrovent HFA. These include blurry vision, dry mouth, problems urinating, constipation, and confusion. 

These drugs include:

  • amitriptyline
  • nortriptyline
Overactive bladder medications

Taking these drugs together will increase your risk for side effects from Atrovent HFA. These include blurry vision, dry mouth, problems urinating, constipation, and confusion. 

These drugs include:

  • oxybutynin
  • tolterodine 
Parkinson’s disease medications

Taking these drugs together will increase your risk for side effects from Atrovent HFA. These include blurry vision, dry mouth, problems urinating, constipation, and confusion.

These drugs include:

  • benztropine
  • trihexyphenidyl
Stomach medications

Taking these drugs together will increase your risk for side effects from Atrovent HFA. These include blurry vision, dry mouth, problems urinating, constipation, and confusion. 

These drugs include:

  • atropine
  • dicyclomine
  • hyoscyamine
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking. Drug warnings

People with narrow-angle glaucoma

Use this drug with caution if you have the eye problem narrow-angle glaucoma. It may make your condition worse. Tell your doctor if you have a history of narrow-angle glaucoma.

People with urinary problems

This drug can make the urinary problems prostatic hypertrophy or bladder-neck obstruction worse. This drug could also make it harder for you to urinate. Let your doctor know if you have urinary problems.

Pregnant women

This drug is a category B pregnancy drug. That means two things: 

  1. Research in animals has not shown a risk to the fetus when the mother takes the drug.
  2. There aren’t enough studies done in humans to show if the drug poses a risk to the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. Animal studies do not always predict the way humans would respond. Therefore, this drug should only be used in pregnancy if clearly needed.

Women who are breast-feeding

This drug may pass into breast milk and may cause side effects in a child who is breast-fed. 

Talk to your doctor if you breast-feed your child. You may need to decide whether to stop breast-feeding or stop taking this medication.

For children

This medicine is only approved to treat chronic obstructive pulmonary disease (COPD), which doesn’t occur in children. This drug shouldn’t be used in children younger than 18 years old.

When to call the doctor

Call your doctor if:

  • This drug isn’t working as well anymore and your symptoms return.
  • Your symptoms get worse.
  • You have to use this drug more frequently than usual.

Allergies

This drug can cause a severe allergic reaction. Symptoms can include: 

  • itching
  • skin rash
  • hives
  • swelling of your lips, tongue, throat, or face
  • trouble breathing or swallowing

Call 9-1-1 or go to the nearest emergency room if you develop these symptoms. 

Don’t take this drug again if you’ve ever had an allergic reaction to it or atropine. Taking it again could be fatal (cause death).

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