Ipratropium bromide

Ipratropium Bromide 250 micrograms/1ml Nebuliser Solution

Ipratropium Bromide 500 micrograms/2ml Nebuliser Solution.

Each ampoule contains ipratropium bromide at 250 micrograms/1ml i.e. 250 micrograms in 1ml and 500 micrograms in 2ml.

Nebuliser Solution.

A clear, colourless solution.

Ipratropium bromide is indicated for the treatment of reversible bronchospasm associated with chronic obstructive pulmonary disease (COPD).

Ipratropium bromide is indicated, when used concomitantly with inhaled beta₂-agonists, for treatment of reversible airways obstruction as in acute and chronic asthma.

This medicinal product is for inhalation use only.

The dosage should be adapted to the individual needs of the patient. In children aged 12 years and under, only Ipratropium Bromide Nebuliser Solution 1 ml should be used. The following doses are recommended:

Adults (including the elderly) and children over 12 years of age:

250 - 500 micrograms (i.e. one vial of 250 micrograms in 1 ml or one vial of 500 micrograms in 2ml) 3 to 4 times daily. The exact starting dose may vary depending on local guidelines.

For treatment of acute bronchospasm, 500 micrograms.

Repeated doses can be administered until the patient is stable. The time interval between the doses may be determined by the physician.

It is advisable not to exceed the recommended daily dose during either acute or maintenance treatment. Daily doses exceeding 2 mg in adults and children over 12 years of age should only be given under medical supervision.

Children 6 - 12 years of age:

250 micrograms (i.e. one vial of 250 micrograms in 1ml) up to a total daily dose of 1mg (4 vials).

The time interval between doses may be determined by the physician.

Children 0 - 5 years of age (for treatment of acute asthma only):

125 - 250 micrograms (i.e. half to one vial of 250 micrograms in 1ml) up to a total daily dose of 1 mg (4 vials).

Ipratropium bromide should be administered no more frequently than 6 hourly in children under 5 years of age.

For acute bronchospasm, repeated doses may be administered until the patient is stable.

If therapy does not produce a significant improvement or if the patient's condition gets worse, medical advice must be sought. In the case of acute or rapidly worsening dyspnoea (difficulty in breathing) a doctor should be consulted immediately.

Ipratropium bromide may be combined with a short-acting beta₂-agonist in the same nebuliser chamber, for simultaneous administration where co-administration is required, in line with local prescribing guidelines. The solution should be used as soon as possible after mixing and any unused solution should be discarded.

Ipratropium bromide can be administered using a range of commercially available nebulising devices. The dose of nebuliser solution may need to be diluted according to local prescribing guidelines and in order to obtain a final volume suitable for the particular nebuliser being used (usually 2 - 4 ml); if dilution is necessary use only sterile sodium chloride 0.9% solution.

Known hypersensitivity to atropine or ipratropium bromide.

Use of the nebuliser solution should be subject to close medical supervision during initial dosing.

Caution is advocated in the use of anticholinergic agents in patients with narrow-angle glaucoma, or with prostatic hyperplasia or bladder-outflow obstruction.

As patients with cystic fibrosis may be prone to gastro-intestinal motility disturbances, ipratropium bromide, as with other anticholinergics, should be used with caution in these patients.

Immediate hypersensitivity reactions following the use of ipratropium bromide have been demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.

There have been isolated reports of ocular complications (i.e. mydriasis, increased intra-ocular pressure, narrow-angle glaucoma, eye pain) when aerosolised ipratropium bromide, either alone or in combination with an adrenergic beta₂-agonist, has come into contact with the eyes during nebuliser therapy.

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 narrow-angle glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately.

Patients must be instructed in the correct administration of ipratropium bromide. Care must be taken not to allow the solution or mist to enter the eyes. It is recommended that the nebulised solution is administered via a mouthpiece. If this is not available and a nebuliser mask is used, it must fit properly. Patients who may be predisposed to glaucoma should be warned specifically to protect their eyes.

None known.

The most common non-respiratory adverse reactions reported in clinical trials are headache, nausea (with or without vomiting) and dryness of the mouth.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard

Palpitation and increases in heart rate have been produced with inhaled doses of 5 mg. Side effects have not been caused by single inhaled doses of 2 mg in adults and 1 mg in children. Single oral doses of 30 mg of ipratropium bromide caused anticholinergic side effects, but these did not require treatment.

Severe overdose is characterized by atropine-like symptoms like tachycardia, tachypnea, high fever and central effects like restlessness, confusion and hallucinations. These symptoms should be treated symptomatically. The use of fysostigmine is not recommended because of worsening of cardiotoxic symptoms and induction of convulsions.

Pharmacotherapeutic group: Anticholinergics, ATC code: R03BB01

Ipratropium bromide is a competitive antagonist of muscarinic acetylcholine receptors. It exhibits its greatest potency on bronchial receptors, whether given intravenously or inhaled, but causes no tachycardia. No anticholinergic effects have been observed on cardiac function, bladder function or in the eye.

Ipratropium bromide is able to inhibit reflex-induced bronchoconstriction following exercise, inhalation of cold air and the early response to inhaled antigens. It also reverses the bronchoconstriction induced by inhaled cholinergic agonists.

Inhalation of 0.04mg of ipratropium from a metered dose aerosol causes bronchodilation, the maximal effect is seen after 30 - 60 minutes, with a duration of 4 hours. This is a dose related effect and use of a nebuliser produces greater bronchodilation, a dose of 0.5mg producing maximal bronchodilation.

Depending on the formulation and the inhalation technique, approximately 10-30 % of the inhaled dose reaches the lungs. The major part of the dose is swallowed.

Because of the negligible gastro-intestinal absorption, the bioavailability of the swallowed dose is only about 2 % of the total dose administered. The part of the dose that reaches the lungs has an almost complete systemic bioavailability and reaches the circulation within a few minutes.

From data on renal excretion (0-24 h) the total systemic bioavailability of inhaled ipratropium bromide is estimated to be 7-28 % (averages from three studies). It can be assumed that this interval is valid for the solution for nebuliser as well.

The kinetic parameters have been calculated from plasma concentrations after intravenous administration. The plasma concentration falls rapidly. The volume of distribution (V_z) is 338 L (approximately 4.6 L/kg). Ipratropium has a low degree of protein binding (<20 %). Because of its ammonium ion structure, ipratropium does not pass the blood-brain barrier. The elimination of ipratropium is biphasic. The half-life of elimination of the drug and metabolites is 3.6 hours. The half-life of the terminal elimination phase is about 1.6 hours.

The average total clearance has been estimated to be 2.3 L/min. About 60 % of the systemic available dose is metabolised, probably in the liver. The main metabolites that are found in the urine have a low affinity for muscarinic receptors and do not possess significant anticholinergic activity.

About 40 % of the systemic available dose is excreted via the kidneys, which corresponds to a renal clearance of 0.9 L/min.

From studies using radioactively labelled ipratropium, less than 10 % of the dose (ipratropium and metabolites) is excreted via bile and faeces. The major part of the radio labelled dose is excreted via the kidneys.

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction, genotoxicity or carcinogenicity.

Sodium Chloride

Water for Injections

Concentrated Hydrochloric Acid (for pH adjustment)

Ipratropium Nebuliser Solution can be diluted only with sterile 0.9% sodium chloride solution.

36 months

Do not store above 25°C. Store in the original package.

The ampoule should be opened immediately before use and any solution remaining after use should be discarded.

Sterile unit dose polyethylene ampoules, containing Ipratropium Bromide Nebuliser Solution are available in two sizes: 1 ml and 2 ml. Ampoules, in strips of 10 overwrapped in aluminium foil, are packed into cartons available in packs of 20 or 60 ampoules. Not all pack sizes may be marketed.

Ipratropium Bromide Nebuliser Solution is for inhalation from an intermittent positive pressure ventilator or from a suitable nebuliser which should be operated according to the manufacturer's instructions.

To open the plastic ampoule, take a strip of ampoules from the foil pack, remove one ampoule, replacing the rest back in the foil pack and replace the foil pack back in the carton. Hold the ampoule upright and open by twisting off the top. Squeeze the liquid into the solution holder of the machine.

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

PL: 20075/0692

23-02-2010

13/03/2018