Consumer medicine information

Apo-Ipratropium

Ipratropium bromide

BRAND INFORMATION

Brand name

APO-Ipratropium

Active ingredient

Ipratropium bromide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Apo-Ipratropium.

What is in this leaflet

Read this leaflet carefully before taking your medicine. Ask your doctor or pharmacist if you do not understand anything or are worried about taking this medicine. This leaflet answers some common questions about APO-Ipratropium. It does not contain all the available information. It does not take the place of talking to your doctor and pharmacist.

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

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

What APO-Ipratropium is used for

APO-Ipratropium contains the active ingredient, ipratropium (as ipratropium bromide).

It is used to prevent or to treat the narrowing of the airways associated with asthma.

It can also be used to relieve any reversible airways blockage associated with problems such as repeated infections affecting the airways.

Ipratropium works by opening up the narrowed airways to assist breathing.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

There is no evidence that ipratropium is addictive.

Before you use it

When you must not use it

Do not use this medicine if you have had an allergic reaction to it or other medicines containing ipratropium or atropine or any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; muscle pain tenderness or joint pain or rash, itching or hives on the skin.

Do not use it if:

  • the packaging is torn or shows signs of tampering
  • the expiry date (EXP) on the pack has passed.
    If you use this medicine after the expiry date has passed it may not work as well.

Talk to your doctor if you are not sure whether you should start using APO-Ipratropium.

Before you start to use it

Tell your doctor if you:

  1. have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
  2. have or have ever had any other health problems/ medical conditions, including:
  • glaucoma, high pressure in the eye
  • difficulty in passing urine
  • constipation, inability to open bowels
  • cystic fibrosis.
  1. are pregnant or intend to become pregnant.
    Your doctor will discuss the risks and benefits of using it during pregnancy.
  2. are breast-feeding or plan to breast-feed.
    Your doctor will discuss the risks and benefits of using it when breast-feeding.
  3. are planning to have surgery or an anaesthetic.
  4. are receiving or are planning to receive dental treatment.

If you have not told your doctor about any of the above, tell them before you begin using this medicine.

Taking other medicines

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

How to use it

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

How much to use

APO-Ipratropium is to be used under the direction of a doctor. Your doctor will recommend a suitable dose for you.

How to use it

APO-Ipratropium is a solution which is used in an efficient device called a nebuliser, which produces a fine mist to breathe in.

Opening instructions for the single dose units:

  1. Twist a single unit downwards to remove from the strip.
  2. Flick the single dose unit so that the solution flows to the bottom.
  3. Hold the base of the single dose unit and break the seal with a quick twisting action.
  4. Snap off the top.
  5. Squeeze the contents of the single dose unit into the nebuliser bowl.

Unless directed otherwise by your doctor or pharmacist, dilute the contents of the single dose unit to 2-3 mL with normal saline and nebulise until the entire volume of solution is inhaled.

Diluted solutions should be freshly prepared before use and any solution remaining in the nebuliser on completion of inhalation should be discarded.

APO-Ipratropium solution must not enter the eyes, be injected or swallowed.

How long to use it

Your doctor will decide how long you will need to use this medicine.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have used too much or swallowed any of the APO-Ipratropium single dose units.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of overdose include:

  • dry mouth
  • fast heart rate
  • eyesight difficulty
  • red, painful eyes with brow-ache or headache and possibly followed by nausea or vomiting.

While you are using it

Things you must do

Tell your doctor if the symptoms of your asthma do not improve within a few days or if they become worse.

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are going to have surgery or an anaesthetic or are going into hospital.

Tell any other doctors, dentists and pharmacists who are treating you that you are using APO-Ipratropium.

Things you must not do

Do not give this medicine to anyone else even if they have the same condition as you.

Do not use it to treat any other conditions unless your doctor tells you to.

Things to be careful of

APO-Ipratropium solution must not enter the eyes, be injected or swallowed.

Be careful driving or operating machinery until you know how APO-Ipratropium affects you. Ipratropium generally does not cause any problems with your ability to drive a car or operate machinery.

Possible Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using APO-Ipratropium. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

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

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

  • dryness of the mouth or throat irritation
  • cough
  • headache
  • nausea
  • indigestion
  • constipation
  • dizziness.

These are all common, usually mild side effects of this medicine.

Tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital if you notice any of the following symptoms:

  • difficulty in passing urine
  • red, painful eyes with brow-ache or headache and possibly followed by nausea or vomiting
  • eye pain
  • dilated pupils of the eyes
  • shortness of breath or difficulty breathing
  • swelling with fluid in the tissues
  • skin rash, may be itchy
  • changes in the way your heart beats e.g. if you notice it beating faster or the beats are irregular.

These are all serious side effects of APO-Ipratropium. You may need urgent medical attention.

Tell your doctor if you notice anything else that is making you feel unwell, even if you think the problems are not connected with this medicine and are not referred to in this leaflet. Other side effects not listed above may also occur in some people.

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

After using it

Storage

Keep APO-Ipratropium single-dose units in their original packs until it is time to use them. If you take the units out of the pack, they may not keep as well.

Keep this medicine in a cool dry place, where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom or near a sink. Do not leave it in the car 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 taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What it looks like

APO-Ipratropium is available in two strengths; 250 mcg/1 mL or 500 mcg/1 mL.

They are a clear, aqueous isotonic, preservative-free nebuliser solution in single-use plastic ampoules.

Available in packs of 30.

Ingredients

Active ingredient:
Each ampoule contains ipratropium bromide [equivalent to either 250 mcg/mL or 500 mcg/mL] as the active ingredient.

Inactive ingredients:

  • sodium chloride
  • hydrochloric acid
  • water for injections.

APO-Ipratropium does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Sponsor

Sponsor

Aspen Pharma Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia

Distributor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

Australian Registration Numbers

  • 250 mcg/1 mL: AUST R 151089
  • 500 mcg/1 mL: AUST R 151090.

Apotex Pty Ltd is the licensee of the registered trademarks APO and APOTEX from the registered proprietor, Apotex Inc.

This leaflet was last updated in May 2013.

Published by MIMS February 2014

BRAND INFORMATION

Brand name

APO-Ipratropium

Active ingredient

Ipratropium bromide

Schedule

S4

 

1 Name of Medicine

Ipratropium bromide.

2 Qualitative and Quantitative Composition

Each ampoule contains ipratropium bromide [equivalent to 250 microgram/mL or 500 microgram/mL ipratropium bromide (anhydrous)]. The excipients include sodium chloride. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Ipratropium is a clear, aqueous isotonic, preservative-free nebuliser solution in single use ampoules.

4 Clinical Particulars

4.1 Therapeutic Indications

APO-Ipratropium is indicated for 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.

4.2 Dose and Method of Administration

APO-Ipratropium can be administered via a range of commercially available nebulising devices. Where wall oxygen is available, nebulising solutions are best administered at a flow rate of 4 to 6 L/min.
Dosage is dependent on the mode of inhalation and the nebuliser used and should be adjusted to suit individual patient requirements.
Daily doses exceeding 2 mg in adults and 1 mg in children under 12 years of age should be given under medical supervision. If the response to the treatment is inadequate, medical advice should be sought so that appropriate measures can be taken. It is advisable not to greatly exceed the recommended daily dose as this suggests additional therapeutic modalities may be needed.
Diluted solutions should be freshly prepared before use and any solution remaining in the nebuliser on completion of inhalation should be discarded.

Adults.

The recommended dosage is 250 to 500 microgram, diluted to 2 to 3 mL with normal saline and nebulised until the entire volume of solution is inhaled, every 6 hours.
In cases of moderate bronchospasm or with assisted ventilation, a dose in the lower range of 1 mL (250 microgram) is recommended. In more severely distressed patients, 500 microgram has been shown to produce optimal bronchodilatation.
Inhalation may be repeated after 2 hours.

Children.

A dose of 250 microgram diluted to 2 to 3 mL with normal saline is recommended for children under 12 years of age, administered in the same way as for adults.

4.3 Contraindications

APO-Ipratropium is contraindicated in patients with a known hypersensitivity to atropine or its derivatives or to any of the ingredients in the APO-Ipratropium preparation.

4.4 Special Warnings and Precautions for Use

Like other drugs with anticholinergic activity, ipratropium bromide 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. Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.
Ipratropium bromide should be used with caution in patients with prostatic hyperplasia or bladder-neck obstruction.
Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angiooedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
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 ipratropium bromide formulations. Therefore, patients must be instructed in the correct handling of APO-Ipratropium, and warned not to allow the solution to enter the eyes. The 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 and corneal congestion, may be signs of acute angle glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory data.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No drug interactions have been reported with ipratropium bromide.
Ipratropium has been shown to produce effective bronchodilatation in patients receiving β-blocking agents.
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 and beta-mimetics are administered simultaneously.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
Care is recommended during pregnancy, particularly in the first trimester. Studies in rats, mice and rabbits showed no embryotoxic or teratogenic effects.
 No specific studies are available to determine the excretion of ipratropium in human breast milk.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

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 http://www.tga.gov.au/reporting-problems.

Body as a whole.

Headache and dizziness have been reported in clinical trials with ipratropium bromide.

Cardiovascular system.

Tachycardia and palpitations, supraventricular tachycardia and atrial fibrillation are anticholinergic side effects which have been reported rarely in patients known to be susceptible.

Gastrointestinal.

Nausea was reported in clinical trials with ipratropium bromide. Gastrointestinal motility disturbances (e.g. constipation, diarrhoea and vomiting), an anticholinergic adverse event has been reported rarely.

Local reactions.

Dryness of the mouth or throat irritation.

Respiratory system.

Cough has been reported in clinical trials with ipratropium bromide. As with other inhaled therapy, including β-agonists, paradoxical bronchoconstriction has been reported. Immediate hypersensitivity reactions may occur after administration of ipratropium bromide solution as demonstrated by rare cases of bronchospasm and oropharyngeal oedema.

Skin and appendages.

Immediate hypersensitivity reactions may occur after administration of ipratropium bromide solution as demonstrated by rare cases of urticaria (including giant urticaria), pruritus, angioedema of the tongue, lips and face, laryngospasm and rash.

Special senses.

Acute angle closure glaucoma following direct eye contact, an anticholinergic side effect has been reported rarely. If the substance enters the eyes by inappropriate handling, mild and reversible disturbance of accommodation may occur. Other ocular complications have also been reported, including, mydriasis, increased intraocular pressure, eye pain.

Urogenital system.

Urinary retention, an anticholinergic side effect has been reported rarely. The risk of urinary retention may be increased in patients with pre-existing outflow tract obstruction.

4.9 Overdose

Accidental overdose by inhalation is unlikely. Single doses of ipratropium 30 mg by mouth (equivalent to sixty 2 mL vials of APO-Ipratropium 0.025% solution) cause anticholinergic side effects, but these are not severe and do not require specific reversal.
No symptoms specific to overdosage have been encountered. In view of the wide therapeutic range and topical administration of ipratropium bromide 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.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ipratropium bromide is an anticholinergic bronchodilator. Ipratropium bromide is a quaternary isopropyl derivative of atropine. The addition of an N isopropyl group distinguishes the molecule from atropine and is responsible for a lower lipid solubility.
Ipratropium bromide differs essentially from the β2-agonists in that it allows bronchodilatation by inhibiting cholinergic bronchomotor tone. That is, the vagal reflexes which mediate bronchoconstriction are blocked.
The onset of bronchodilator response with ipratropium is seen within three to five minutes of administration and peak response is reached approximately 1.5 to 2 hours after inhalation. This time course of action differs from the β2-agonists. The duration of significant bronchodilator action with ipratropium is up to six hours.
APO-Ipratropium and β2-agonists may be used in combination drug therapy. There is evidence that in patients who respond to ipratropium, the concurrent administration of ipratropium and β2-agonists results in greater relief of bronchospasm than either drug given alone. Addition of APO-Ipratropium to the treatment regimen may enable some gradual reduction of corticosteroid dosage.
APO-Ipratropium inhibits acetylcholine induced bronchospasm and provides partial protection against histamine and allergen induced bronchospasm. No significant change in sputum viscosity, sputum volume or mucociliary clearance has been reported.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

No pharmacokinetic data are available on the ipratropium bromide nebulising solution. However, from limited pharmacokinetic data using an ipratropium bromide metered dose aerosol in humans, it has been shown that approximately 5% of an inhaled dose is absorbed systemically and, thus, very low plasma levels are reached. Based on this data, it may be assumed that a similar pharmacokinetic pattern applies with the ipratropium nebulising solution. However, it is suggested that the systemic levels are likely to be higher with administration of the nebulising solution due to the increased dose administered.

Distribution.

As with other substances administered by inhalation, most of the dose enters the gastrointestinal tract, is unabsorbed and excreted in the faeces.

Metabolism.

A total of 8 metabolites with little or no anticholinergic activity have been detected.

Excretion.

The elimination half-life in healthy volunteers is 3.5 hours (range 1.5 to 4 hours).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, hydrochloric acid and water for injection.

6.2 Incompatibilities

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

6.3 Shelf Life

2 years.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

1 mL plastic ampoules in packs of 30.

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 is a white or almost white crystalline powder. The powder is soluble in water, slightly soluble in ethanol and freely soluble in methanol.
Chemical Name: (1R,3r,5S,8r)-3-[[(2RS)-3-Hydroxy-2-phenylpropanoyl] oxy]-8-methyl-8-(1-methylethyl)-8-azoniabicyclo [3.2.1] octane bromide monohydrate.
Molecular Formula: C20H30NO3Br,H2O. Molecular Weight: 430.4.

Chemical structure.


CAS number.

66985-17-9.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes