Consumer medicine information

Atrovent Inhalation Solution

Ipratropium bromide

BRAND INFORMATION

Brand name

Atrovent Nebulising Solution

Active ingredient

Ipratropium bromide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Atrovent Inhalation Solution.

What is in this leaflet

This leaflet answers some common questions about Atrovent Inhalation Solution.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Atrovent Inhalation Solution against the benefits it is expected to have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

This leaflet was last updated on the date at the end of this leaflet. More recent information may be available. The latest Consumer Medicine Information is available from your pharmacist, doctor, or from www.medicines.org.au and may contain important information about the medicine and its use of which you should be aware.

Keep this leaflet with the medicine. You may need to read it again.

What Atrovent Inhalation Solution is used for

Atrovent Inhalation Solution is used to treat:

  • asthma
  • chronic obstructive bronchitis
  • people who have difficulty breathing during or after surgery using assisted ventilation.

Asthma is a lung condition where the lining of the lungs becomes inflamed (red and swollen), making it difficult to breathe. This may be due to an allergy to house dust mites, smoke or other irritants.

Chronic obstructive bronchitis is a lung condition that can cause difficulty in breathing, wheeziness and constant coughing.

Atrovent Inhalation Solution contains the active ingredient ipratropium bromide monohydrate. It belongs to a group of medicines called anticholinergic bronchodilators.

Atrovent Inhalation Solution opens up the air passages in people suffering from asthma, chronic bronchitis and difficulty breathing during or after surgery.

It begins to act quickly after use but may take up to 2 hours to give maximum benefit.

Ask your doctor if you have any questions about why Atrovent Inhalation Solution has been prescribed for you. Your doctor may have prescribed Atrovent Inhalation Solution for another reason.

There is no evidence that Atrovent Inhalation Solution is addictive.

Atrovent Inhalation Solution is available only with a doctor's prescription.

Before you use Atrovent Inhalation Solution

When you must not use it

Do not use Atrovent Inhalation Solution if you have an allergy to:

  • ipratropium bromide monohydrate
  • similar medicines which contain atropine or medicines like atropine
  • any of the ingredients listed at the end of this leaflet
  • any other anticholinergic medicines.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or troubled breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use Atrovent Inhalation Solution after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using Atrovent Inhalation Solution, contact your doctor or pharmacist.

Before you start to use it

Tell your doctor or pharmacist if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. Your doctor or pharmacist will discuss the possible risks and benefits of using Atrovent Inhalation Solution during pregnancy.

Tell your doctor or pharmacist if you are breastfeeding or plan to breastfeed. Your doctor or pharmacist will discuss the possible risks and benefits of using Atrovent Inhalation Solution during breastfeeding.

Tell your doctor or pharmacist if you have or have had any of the following medical conditions:

  • glaucoma (high pressure in the eye)
  • difficulty or pain when passing urine
  • constipation
  • cystic fibrosis
  • hyper reactive airways.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using Atrovent Inhalation Solution.

Using other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Atrovent Inhalation Solution may interfere with each other. These include:

  • medicines used to treat heart problems such as adrenaline
  • medicines used to treat asthma or a lung condition called chronic obstructive pulmonary disease (COPD) such as theophylline, salbutamol or tiotropium
  • other nebuliser solutions such as disodium cromoglycate that contain the preservative benzalkonium chloride.

This is because some nebuliser solutions may not mix well with Atrovent Inhalation Solution and may need to be nebulised separately.

These medicines may be affected by Atrovent Inhalation Solution, or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor may prescribe Atrovent Inhalation Solution with other medicines that relax the air passages for additional symptom relief.

Check with your doctor or pharmacist before mixing other nebuliser solutions with Atrovent Inhalation Solution. Some nebulised medicines may not mix well with Atrovent Inhalation Solution and may need to be nebulised separately.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Atrovent Inhalation Solution.

How to use Atrovent Inhalation Solution

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

Atrovent Inhalation Solution is intended for inhalation with suitable nebulising equipment and must not be swallowed.

Diluted solutions should be freshly prepared before use.

At the end of inhalation, leftover solution from the nebuliser bowl should be discarded.

Atrovent Inhalation Solution should not be used if the bottle has been opened for more than 28 days.

After this period, a new Atrovent Inhalation Solution bottle should be used.

Take the following steps in using Atrovent Inhalation Solution and if you have any problems, ask your doctor or pharmacist for assistance.

  1. Get your nebuliser ready by following the manufacturer's instructions and the advice of your doctor.
  2. Place the prescribed number of drops into the nebuliser bowl.
    The dropper insert on top of the bottle delivers 1 mL of Atrovent Inhalation Solution per 20 drops. Each 1 mL of Atrovent Inhalation Solution contains 261 micrograms of ipratropium bromide monohydrate (equivalent to 250 micrograms of ipratropium bromide).
    To make the dropper function, tap lightly on the bottom of the bottle.
  3. If dilution is necessary this should be carried out using normal saline and as instructed by your doctor.
  4. Assemble the nebuliser and use it as directed by your doctor.
  5. After nebulisation follow the manufacturer's instructions about cleaning your nebuliser.

If you are not sure how to use a nebuliser mask, or do not understand the instructions on the box, ask your doctor or pharmacist for help.

Children should only use Atrovent Inhalation Solution on medical advice and with the help of an adult.

Fit the nebuliser mask to your or your child's nose and mouth before nebulising and inhaling Atrovent Inhalation Solution to prevent the mist from contacting the eyes.

Should the mist contact the eyes, immediately flush your eyes with cold tap water for several minutes.

If you find it difficult to breathe in and use your nebulising mask at the same time, talk to your doctor or pharmacist. They may be able to recommend another method.

How much to use

The usual doses for adults and children are stated below.

Adults:
1 to 2 mL diluted to 2-3 mL with normal saline and nebulised until the entire volume of solution is inhaled, 4 times daily.

Children:
1 mL diluted to 2-3 mL with normal saline and nebulised until the entire volume of solution is inhaled, 4 times daily.

Depending on your condition and specific needs, your doctor may advise you to take a different dose.

When to use it

If your doctor has advised you to use Atrovent Inhalation Solution regularly, then use your medicine at about the same time each day. Using it at the same time each day will have the best effect. It will also help you remember when to use it.

If you forget to use it

If it is almost time for your next dose, skip the dose you missed and have your next dose when you are meant to.

Otherwise, use it as soon as you remember, and then go back to using your medicine as you would normally.

Do not use a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

How long to use it

Continue using Atrovent Inhalation Solution for as long as your doctor tells you.

Atrovent Inhalation Solution helps control your condition, but does not cure it. It is important to keep using it even if you feel well.

If you take too much (overdose)

Immediately telephone your doctor or pharmacist or the Poisons Information Centre (telephone 13 11 26) for advice or go to Emergency at the nearest hospital, if you think that you or anyone else may have used too much Atrovent Inhalation Solution. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include:

  • fast or irregular heart beat
  • dry mouth
  • blurred vision.

While you are using Atrovent Inhalation Solution

Things you must do

Stop using Atrovent Inhalation Solution and tell your doctor immediately if you get sudden tightness of the chest, coughing, wheezing or breathlessness immediately after using Atrovent Inhalation Solution. These may be signs of a condition called bronchospasm.

If you have an Asthma Action Plan that you have agreed with your doctor, follow it closely at all times.

If you find that the usual dose of Atrovent Inhalation Solution is not giving as much relief as before, or you need to use it more often, contact your doctor so that your condition can be checked. This is important to ensure your breathing problem is controlled properly.

Continue using Atrovent Inhalation Solution for as long as your doctor or pharmacist tells you.

Keep all your doctor's appointments so that your progress can be checked.

Contact your doctor immediately if your breathing suddenly becomes more difficult after using Atrovent Inhalation Solution. This may be a sign of an allergic reaction.

Contact your doctor immediately if you experience irritation or a feeling of having something in the eye, or any disturbances with your sight (blurred vision, visual halos or coloured images) together with red eyes, during or after using Atrovent Inhalation Solution. This may mean that you have developed a serious eye condition called narrow-angle glaucoma. This can happen if the solution gets in your eyes.

Tell any other doctors, dentists, and pharmacists who are treating you that you are using Atrovent Inhalation Solution.

If you are about to start any new medicine, tell your doctor or pharmacist that you are using Atrovent Inhalation Solution.

If you plan to have surgery, tell the surgeon or anaesthetist that you are using Atrovent Inhalation Solution. It may affect other medicines during surgery.

If you become pregnant while using Atrovent Inhalation Solution tell your doctor or pharmacist immediately.

Things you must not do

Do not take any other medicines for your breathing problems without checking with your doctor.

Do not give Atrovent Inhalation Solution to anyone else, even if they have the same condition as you.

Do not use Atrovent Inhalation Solution to treat any other complaints unless your doctor or pharmacist tells you to.

Do not stop using Atrovent Inhalation Solution or lower the dosage, without checking with your doctor or pharmacist.

Do not allow the Atrovent Inhalation Solution to enter the eyes.

Things to be careful of

Be careful driving or operating machinery until you know how Atrovent Inhalation Solution affects you. Atrovent Inhalation Solution may cause dizziness and blurred vision in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous. Children should be careful when performing physical activities.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Atrovent Inhalation Solution. This medicine helps most people with asthma or chronic obstructive bronchitis, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

If you get any side effects, do not stop using the Atrovent Inhalation Solution without first talking to your doctor or pharmacist.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • headache
  • dizziness
  • dry or sore mouth
  • throat irritation
  • cough
  • nausea, vomiting
  • a change in bowel movements, e.g. constipation, diarrhoea, wind, indigestion, reflux (an unusual backflow of fluid).

These are the more common side effects of Atrovent Inhalation Solution. Usually they are mild and short lived.

Tell your doctor as soon as possible if you experience difficulty passing urine. This is a serious side effect that may require medical attention.

If any of the following happen, tell your doctor immediately or go to Emergency at the nearest hospital:

  • difficulty breathing or worsening of your breathing problems
  • swelling of the throat
  • fast or irregular heart beat, also called palpitations
  • pounding heart beat
  • allergic reaction (shortness of breath, wheezing or troubled breathing; swelling of the face, lips, tongue or other parts of the body, rash, itching or hives on the skin)
  • irritation or a feeling of having something in the eye, red eyes, dilated pupils, blurred vision, visual halos or coloured images.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some people.

After using Atrovent Inhalation Solution

Storage

Keep your Atrovent Inhalation Solution in a cool, dry place where the temperature stays below 30°C. Discard unused contents 28 days after opening.

Do not store Atrovent Inhalation Solution or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using Atrovent Inhalation Solution or it has passed its expiry date, ask your pharmacist what to do with any medicine that is left over.

Product Description

What it looks like

Atrovent Inhalation Solution is a clear, colourless solution, supplied in bottles containing 20 mL of solution.

Ingredients

Each mL of Atrovent Inhalation Solution contains 261 micrograms of ipratropium bromide monohydrate (equivalent to 250 micrograms of ipratropium bromide) as the active ingredient.

It also contains:

  • sodium chloride
  • benzalkonium chloride
  • disodium edetate
  • hydrochloric acid
  • purified water.

Atrovent Inhalation Solution does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Atrovent Inhalation Solution is supplied in Australia by:

Boehringer Ingelheim Pty Limited
ABN 52 000 452 308
Sydney NSW
www.boehringer-ingelheim.com.au

This Consumer Medicine Information was revised in October 2019.

® Atrovent is a registered trademark of Boehringer Ingelheim

© Boehringer Ingelheim Pty Limited 2019

Australian Registration Number:

AUST R 39953

Published by MIMS January 2020

BRAND INFORMATION

Brand name

Atrovent Nebulising Solution

Active ingredient

Ipratropium bromide

Schedule

S4

 

1 Name of Medicine

Ipratropium bromide monohydrate.

2 Qualitative and Quantitative Composition

Each 1 mL of Atrovent Inhalation Solution contains ipratropium bromide monohydrate 261 micrograms (equivalent to 250 micrograms ipratropium bromide).
Each 1 mL of Atrovent Unit Dose Vial (UDV) contains ipratropium bromide monohydrate 261 micrograms (equivalent to 250 micrograms ipratropium bromide).
Each 1 mL of Atrovent Adult Unit Dose Vials (UDV) contains ipratropium bromide monohydrate 522 micrograms (equivalent to 500 micrograms ipratropium bromide).

Excipients with known effect.

Atrovent Inhalation Solution contains 0.1 mg benzalkonium chloride in each mL and disodium edetate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Atrovent is an inhalation solution.

Atrovent Inhalation Solution.

Clear, colourless or almost colourless liquid, free from suspended particles in multidose bottle. Contains benzalkonium chloride as the preservative.

Atrovent UDV.

Preservative free, clear, colourless or almost colourless liquid, free from suspended particles.

Atrovent Adult UDV.

Preservative free, clear, colourless or almost colourless liquid, free from suspended particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Moderate asthmatic attacks; chronic forms of asthma; asthma in patients with diminished cardiac reserve; chronic obstructive bronchitis with bronchospasm; bronchospasm during or after surgery, use during assisted ventilation with a respirator.
Administration of Atrovent via a nebuliser is intended for those patients who cannot use a metered dose aerosol.

4.2 Dose and Method of Administration

Atrovent solution can be administered via a range of commercially available nebulising devices. Where wall oxygen is available, solutions are best administered at a flow rate of 6-8 litres per minute.
Dosage is dependent on the mode of inhalation and the quality of nebulisation. The duration of inhalation can be controlled by the dilution volume. It is advisable not to greatly exceed the recommended daily dose as this suggests additional therapeutic modalities may be needed.

Note.

20 drops from the dropper insert in the multidose bottle equal approximately 261 micrograms of ipratropium bromide monohydrate (equivalent to 250 micrograms ipratropium bromide).
The dosage should be adapted to the individual requirements of the patient; patients should also be kept under medical supervision during treatment. Unless otherwise prescribed, the following doses are recommended.

Adults.

The recommended dose is 261-522 micrograms [equivalent to 250-500 micrograms ipratropium bromide], 4 times daily, diluted to 2-3 mL with normal saline, and nebulised until the entire volume of solution is consumed. Daily dose exceeding 2.088 mg (equivalent to 2 mg ipratropium bromide) in adults should be given under medical supervision.
In cases of moderate bronchospasm or with assisted ventilation, a dose in the lower range of 261 micrograms (equivalent to 250 micrograms ipratropium bromide) is recommended. In more severely distressed patients, 522 micrograms ipratropium bromide monohydrate (equivalent to 500 micrograms ipratropium bromide) has been shown to produce optimal bronchodilation.
Atrovent can be administered combined with an inhaled β2-agonist.

Children.

The recommended dose is 261 micrograms (equivalent to 250 micrograms ipratropium bromide), 4 times daily, diluted to 2-3 mL with normal saline and nebulised until the entire volume of solution is consumed. Daily dose exceeding 1.044 mg (equivalent to 1 mg ipratropium bromide) in children ≤ 12 years of age should be given under medical supervision.
Atrovent can be administered combined with an inhaled β2-agonist.
It is advisable not to greatly exceed the recommended daily dose.
If therapy does not produce a significant improvement or if the patient's condition gets worse, medical advice must be sought in order to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnoea (difficulty in breathing) a doctor should be consulted immediately.

4.3 Contraindications

Known hypersensitivity to atropine or its derivatives (such as the active substance ipratropium bromide), or to any of the other ingredients of Atrovent (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

Atrovent Inhalation Solution contains 0.1 mg benzalkonium chloride in each mL.
Benzalkonium chloride may cause wheezing and breathing difficulties. Patients with asthma are at an increased risk for these adverse events.

Hypersensitivity.

Immediate hypersensitivity reactions may occur after administration of Atrovent, as demonstrated by rare cases of urticaria, angio-oedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.

Paradoxical bronchospasm.

As with other inhaled medicines Atrovent may result in paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs Atrovent should be discontinued immediately and substituted with an alternative therapy.

Anticholinergic effects.

Like other drugs with anticholinergic activity, ipratropium bromide monohydrate should be avoided or used with caution in patients where atropine-like effects may precipitate or exacerbate a pre-existing clinical condition. Patients at particular risk are those with eyes with narrow iridocorneal angles as acute angle closure glaucoma may be precipitated, or patients with a tendency towards urinary retention or constipation.

Ocular complications.

Atrovent should be used with caution in patients predisposed to narrow angle glaucoma.
There have been isolated reports of ocular complications (mydriasis, increased intraocular pressure, acute angle glaucoma, eye pain) as a result of direct eye contact of aerolised ipratropium bromide monohydrate, either alone or in combination with an adrenergic β2-agonist. Thus, patients must be instructed in the correct administration of Atrovent, and warned not to allow the solution or mist to enter the eyes. A nebuliser mask must be fitted properly during inhalation.
Patients who may be predisposed to glaucoma should be specifically warned to protect their eyes. Eye pain or discomfort, blurred vision, visual halos or coloured images, in association with red eyes from conjunctival congestion and corneal oedema, may be signs of acute angle closure glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately.

Renal and urinary effects.

Atrovent should be used with caution in patients with pre-existing urinary outflow tract obstruction (e.g. prostatic hyperplasia or bladder neck obstruction).

Gastro-intestinal motility disturbances.

Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.

Local effects.

Atrovent Inhalation Solution in the multidose bottle contains benzalkonium chloride and disodium edetate. When inhaled these agents may cause bronchospasm in sensitive patients with hyper-reactive airways. If the multidose nebulising solution is prescribed, it is suggested that patients be monitored for their FEV1, and if the FEV1 falls, therapy with the preservative free Unit Dose Vials or Metered Dose Aerosol should be used.

Use in the elderly.

No data available.

Paediatric use.

Paediatric patients can use Atrovent inhalation at the recommended dose.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The chronic co-administration of Atrovent inhalation with other anticholinergic drugs has not been studied. Therefore, the chronic co-administration of Atrovent with other anticholinergic drugs is not recommended.
Beta-Adrenergics and xanthine preparations may intensify the bronchodilatory effect.
The risk of acute glaucoma in patients with a history of narrow angle glaucoma (see Section 4.4 Special Warnings and Precautions for Use) may be increased when nebulised ipratropium bromide monohydrate and beta-mimetics are administered simultaneously.

Physical compatibility.

Atrovent Inhalation Solutions and disodium cromoglycate inhalation solutions that contain the preservative benzalkonium chloride should not be administered simultaneously in the same nebuliser as precipitation may occur.
Atrovent UDVs and disodium cromoglycate inhalation solutions should not be administered simultaneously in the same nebuliser.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Clinical data on fertility are not available for ipratropium bromide monohydrate.
(Category B1)
Care is recommended during pregnancy, particularly in the first trimester. The safety of Atrovent during pregnancy has not been established. The benefits of using Atrovent when pregnancy is confirmed or suspected must be weighed against possible hazards to the foetus. Studies in rats, mice and rabbits showed no embryo-toxic nor teratogenic effects.
No specific studies are available to determine the excretion of ipratropium bromide in human breast milk. Although lipid insoluble quaternary cations pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to an important extent, especially when administered by inhalation. However, as many drugs are excreted into breast milk, caution should be exercised when Atrovent is administered to breastfeeding mothers.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as dizziness, accommodation disorder, mydriasis and blurred vision during treatment with Atrovent. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
Many of the listed undesirable effects can be assigned to the anticholinergic properties of Atrovent. As with all inhalation therapy Atrovent may show symptoms of local irritation.
The most frequent side effects reported in clinical trials were headache, dizziness, throat irritation, cough, gastrointestinal disorders (including constipation, diarrhoea, gastrointestinal motility disorder, dry mouth, nausea, stomatitis, oedema mouth, and vomiting).
If the substance enters the eyes by inappropriate handling, mild and reversible disturbance of accommodation may occur. Other ocular complications have also been reported (see Section 4.4 Special Warnings and Precautions for Use). However, acute angle-closure glaucoma has been reported following direct eye contact.
Allergic-type reactions such as angio-oedema of the tongue, lips and face, may occur.
The following adverse reactions have been reported during use of Atrovent in clinical trials and during the post-marketing experience at the following frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000). See Table 1.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
No symptoms specific to overdosage have been encountered. In view of the wide therapeutic range and topical administration of Atrovent inhalation solutions, no serious anticholinergic symptoms are to be expected. Minor systemic manifestations of anticholinergic action, including dry mouth, visual accommodation disturbances and tachycardia may occur.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pharmacotherapeutic group: Anticholinergics.
ATC code: R03BB01.
Atrovent is an anticholinergic bronchodilator. It appears to inhibit vagally mediated reflexes by antagonising the action of acetylcholine, the transmitter agent released from the vagal nerve. Anticholinergics prevent the increase in intracellular calcium concentration caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. Bronchodilation following inhalation of Atrovent is primarily a local, site specific effect at the bronchial smooth muscle. Atrovent has no deleterious effect on airway mucous secretion or mucociliary clearance.
The time course of action of Atrovent also differs from the β2-agonists in that although the onset of bronchodilator response is seen within 3-5 minutes of administration, peak response is not reached until 1.5-2 hours after inhalation. The duration of significant bronchodilator action is up to 6 hours.
Atrovent may be used in combination with β2-agonists. There is evidence that in patients who respond to Atrovent, the concurrent administration of Atrovent and β2-agonists produces a greater relief of bronchospasm than either drug given alone.
Atrovent inhibits acetylcholine-induced bronchospasm and provides partial protection against histamine and allergen-induced bronchospasm.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following inhalation, 10 to 30% of the dose (depending on the formulation and inhalation technique) is generally deposited in the lungs. The major part of the dose is swallowed and passes into the gastrointestinal tract. Due to the low gastrointestinal absorption of ipratropium bromide, the bioavailability of the portion of the dose swallowed accounts for approximately 2% of the dose. This fraction of the dose does not make a relevant contribution to the plasma concentrations of the active ingredient. The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes) and has nearly complete systemic availability.
From renal excretion data (0-24 hours), the total systemic bioavailability (pulmonary and gastrointestinal portions) of inhaled doses of ipratropium bromide was estimated to be in the range 7 to 28%. This is also a valid range for inhalation from Atrovent CFC-free because the kinetic results (renal excretion, AUC and Cmax) from the CFC-free and the CFC containing formulations are approximately comparable.

Distribution.

Kinetic parameters describing the disposition of ipratropium bromide were calculated from plasma concentrations after intravenous administration. A rapid biphasic decline in plasma concentrations is observed. The volume of distribution (Vz) is 338 L (approximately 4.6 L/kg). The half-life of the terminal elimination phase is about 1.6 hours. The drug is less than 20% bound to plasma proteins. The ipratropium ion does not cross the blood-brain barrier, consistent with the ammonium structure of the molecule.
The main urinary metabolites bind poorly to the muscarinic receptor and have no activity.

Metabolism.

The mean total clearance of the drug is 2.3 L/min. The major portion, approximately 60% of the systemically available dose, is eliminated by metabolic degradation, probably in the liver.

Excretion.

Approximately 40% of the systemically available dose is cleared via urinary excretion, corresponding to an experimental renal clearance of 0.9 L/min. After oral dosing less than 1% of the dose is renally excreted, indicating an insignificant absorption of ipratropium bromide from the gastrointestinal tract.
In excretion balance studies, after intravenous administration of a radioactive dose, less than 10% of the drug-related radioactivity (including parent compound and all metabolites), are excreted via the biliary-faecal route. The dominant excretion of drug-related radioactivity occurs via the kidneys.

5.3 Preclinical Safety Data

Genotoxicity.

Results of various mutagenicity studies (Ames test, mouse dominant lethal test, mouse micronucleus test and chromosome aberration of bone marrow in Chinese hamsters) were negative.

Carcinogenicity.

Two-year oral carcinogenicity studies in rats and mice have revealed no carcinogenic potential at dietary doses up to 6 mg/kg/day for Atrovent.

6 Pharmaceutical Particulars

6.1 List of Excipients

Atrovent Inhalation Solution - multidose bottles and Atrovent UDVs contain sodium chloride, hydrochloric acid and purified water. The multidose solution also contains benzalkonium chloride as preservative and disodium edetate as stabiliser.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store the bottles at below 30°C. After opening the multidose bottle, the solution should be used as soon as possible and any unused solution should be discarded after 28 days.
Store the unopened Unit Dose Vials (UDV) at below 25°C. Protect from light. Diluted solutions should be freshly prepared before use and any solution remaining in the nebuliser, on completion of inhalation, should be discarded.

6.5 Nature and Contents of Container

Atrovent Inhalation Solution are available in glass bottles of 20 mL.
Atrovent UDV are available in LDPE vials; packs of 10* or 30 vials of 1 mL.
Atrovent Adult UDV are available in PE vials; packs of 10* or 30 vials of 1 mL.
* Not currently distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Ipratropium bromide monohydrate is a synthetic quaternary ammonium compound, chemically related to atropine. The addition of an N-isopropyl group distinguishes the molecule from atropine and is responsible for a lower lipid solubility.
Ipratropium bromide monohydrate is a white or off-white crystalline substance. It is freely soluble in methanol, soluble in water and sparingly soluble in ethanol 96% (v/v).
The chemical name for ipratropium bromide (as monohydrate) is (1R,3r, 5S,8r)-3-[(RS)-(3-hydroxy-2-phenyl-propanoyl)-oxy]-8-methyl-8-(1-methylethyl)-8-azoniabicyclo[3.2.1]octane bromide monohydrate.
The molecular formula is C20H30NO3Br.H2O and the molecular weight is 430.4.

Chemical structure.

Ipratropium bromide monohydrate has the following structural formula:

CAS number.

66985-17-9.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes