Ipratropium Bromide Inhalation Solution.
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ipratropium Bromide Inhalation Solution.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Ipratropium Bromide 250mcg/ml (250mcg and 500mcg ampoules).
3 PHARMACEUTICAL FORM
Inhalation solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of reversible airways obstruction.
4.2 Posology and method of administration
Adults:
0.4-2.0ml solution (100-500mcg) up to 4 times daily.
Children aged 3-14 years:
0.4-2.0ml solution (100-500mcg) up to 3 times daily.
Elderly:
There is no specific information on the use of ipratropium bromide nebuliser solution in the elderly.
Route of Administration
By inhalation from an intermittent positive pressure ventilator or from a suitable nebuliser. If it is necessary to dilute the solution, sterile sodium chloride solution 0.9% should be used.
4.3 Contraindications
Known hypersensitivity to atropine. Known hypersensitivity to any of the ingredients of Ipratropium Bromide Inhalation Solution.
4.4 Special warnings and precautions for use
Use of the nebuliser solution should be subject to close medical supervision during initial dosing. There have been rare reports of paradoxical bronchospasm associated with administration of ipratropium bromide nebuliser solution. The patient should be advised to seek medical advice should a reduced response become apparent.
Patients must be instructed in the correct administration of Ipratropium Bromide Inhalation Solution and warned not to allow the mist or solution to enter the eyes. Acute angle-closure glaucoma has been reported rarely when ipratropium bromide nebuliser solution has been used in conjunction with nebulised ^2-agonist bronchodilators. Protection of the eyes appears to prevent any increase in intra-ocular pressure and patients who may be susceptible to glaucoma should be warned specifically of the need for ocular protection. Inhaled doses of ipratropium bromide nebuliser solution up to 1mg have not been associated with elevation of intra-ocular pressure.
Caution is advised in the use of anticholinergic agents in patients with prostatic hypertrophy.
4.5 Interaction with other medicinal products and other forms of interaction
None known.
4.6 Pregnancy and lactation
Ipratropium bromide has been in general use for several years and there is no definite evidence of ill-consequence during pregnancy; animal studies have shown no hazard. Nevertheless, medicines should not be used during pregnancy, especially during the first trimester, unless the expected benefit is thought to outweigh any possible risk to the foetus.
No information is available on excretion of ipratropium bromide in breast milk and therefore use of ipratropium should be avoided in breast-feeding mothers.
Dizziness and blurred vision have been reported. If affected, the patient should be warned not to drive or operate machinery.
4.8 Undesirable Effects
Adverse events are listed below by system organ class and frequencies observed from spontaneous reporting and in clinical trials.
> 1/10
> 1/100<1/10 >1/1,000<1/100 >1/10,000<1/1,000 >1/10,000
Cannot be estimated from available data
Immune system disorders
Urticaria Uncommon
Anaphylactic reaction Rare
Angioedema of tongue lips and face Rare
Nervous system disorders
Headache Common
Dizziness Common
Eye disorders
Ocular accommodation disturbances Angle closure glaucoma Eye pain Mydriasis
Intraocular pressure increased1 Anisocoria
Uncommon
Uncommon
Rare
Rare
Rare
Not known
Cardiac disorders
Tachycardia
Palpitations
Supraventricular tachycardia Atrial fibrillation
Uncommon
Rare
Rare
Rare
Paradoxical bronchospasm Common
Laryngospasm Rare
Gastro-intestinal disorders
Common
Common
Common
Dry mouth Vomiting and Nausea G.I Motility disorders (Constipation, diarrhoea)
Skin and subcutaneous disorders
Skin Rash Uncommon
Pruritus Uncommon
Renal and Urinary disorders
Urinary retention2 Rare
1 Particularly in patients predisposed to narrow angle glaucoma.
2
Particularly in patients suffering from prostatic hyperplasia.
There is no evidence that in the therapeutic range ipratropium bromide has any effect on bronchial secretion.
4.9 Overdose
Inhaled doses of 5mg produce an increase in heart rate and palpitations, but single doses of 2mg have been given to adults and 1mg to children without causing side-effects. Single doses of ipratropium bromide of 30mg per mouth cause anticholinergic side-effects, but these are not severe and do not require specific reversal.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ipratropium bromide produces bronchodilation by competitive inhibition of cholinergic receptors on bronchial smooth muscle, which antagonises the action of acetylcholine at its membrane-bound receptor and thus decreases the formation of cGMP. It may also inhibit acetylcholine-enhanced release of chemical mediators by blocking cholinergic receptors at the surface of mast cells.
As with other inhaled anticholinergic agents, ipratropium bromide has been found, in experimental bronchospasm, to be most effective against cholinergic challenges, providing little protection against serotonin or histamine-induced bronchospasm, and a moderate protection against bronchospasm induced by propranolol or common allergens. Trials of exercise induced bronchospasm have produced varying results. In those studies that found no protection, ipratropium bromide was usually administered just prior to an exercise challenge, whilst those showing partial or total protection monitored the response over a longer period, allowing adequate time for onset of effect.
After inhalation of ipratropium bromide, the onset of action is within 15 minutes, with a mean dose dependent duration of effect of three to five hours. The peak bronchodilatory effect occurs between one and two hours after inhalation of the drug, with 50% of the eventual bronchodilation occurring by three minutes and 80% occurring within 30 minutes after doses of 40-160mcg.
Maximal changes in objective measures of pulmonary function are evident within one to two hours and persist for at least four hours. Although increasing the dose of ipratropium bromide from 40 to 160mcg does not substantially increase the degree of bronchodilation, a dose-duration relationship exists. Nebulised doses of 80 to 500mcg have been reported to have a duration of action up to six hours.
Antimuscarinic agents typically inhibit mucociliary clearance and inhibit secretions of the nose, mouth, pharynx and bronchi. However, inhaled ipratropium bromide has virtually no effect on sputum viscosity or volume and, in contrast to atropine, it does not affect mucociliary function in the respiratory tract.
No cardiovascular changes have been seen following inhalation of therapeutic doses in patients, or after up to 400mcg in healthy subjects.
Inhibition of gastric secretions has been observed following oral administration of ipratropium bromide. The effect is slow in onset (peak 6-7 hours) but long in duration (more than 12 hours).
5.2 Pharmacokinetic properties
Ipratropium bromide has poor systemic absorption after oral and inhaled administration. The absolute amount of ipratropium bromide in the blood after oral administration is approximately 0.5% of the administered dose. Blood concentrations after inhalation are about 1000 times lower than concentrations achieved after oral administration of equipotent bronchodilatory doses. Although specific data regarding the distribution of inhaled ipratropium bromide are not available, the drug diffuses rapidly into tissues after IV of IM administration. Ipratropium bromide is partially metabolised to 8 metabolites (6 in very small quantities) that have little, if any, anticholinergic effect. The main metabolite is the quaternary tropinium salt formed by enzymatic hydrolysis of the ester. The elimination half life for all routes of administration is 3.2-3.8 hours. After inhalation, the parent drug and metabolites are eliminated in the urine and faeces, with approximately 3.2% recovered in the urine and 69% recovered in the faeces after six days.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Water, sodium chloride, dilute hydrochloric acid, sodium hydroxide.
6.2 Incompatibilities
None known.
Ipratropium Bromide Inhalation Solution should only be diluted with sterile
0.9% sodium chloride solution.
6.3 Shelf life
2 years for both the 1ml and 2ml solutions.
6.4 Special precautions for storage
Store in a dry place below 25°C; protect from light.
Discard remaining solution after use.
6.5 Nature and contents of container
Blocks of 10 plastic ampoules wrapped in an aluminium pouch, each ampoule containing 1ml or 2ml of a clear, colourless solution. Cartons of 20 or 60 ampoules.
6.6 Special precautions for disposal
1. Read the instructions provided with the nebuliser and ensure you are familiar with its operation.
2. Prepare the nebuliser for use.
3. Separate an ampoule from the strip by carefully pulling and twisting. Never use one that is already open.
4. Hold the ampoule upright and twist off the tab. Use the contents of the ampoule immediately after opening.
5. Squeeze the appropriate amount of the ampoule contents (usually all the contents) into the nebuliser reservoir. If dilution is necessary, this should be carried out using only sterile normal saline solution as instructed by the doctor.
6. Assemble the nebuliser and use as instructed by the doctor. Care should be taken to ensure that the nebuliser mist (or the solution) does not enter the eyes. Eye protection is recommended for people with a history of glaucoma.
7. After nebulisation, throw away any remaining solution and clean the nebuliser as instructed.
7 MARKETING AUTHORISATION HOLDER
Focus Pharmaceuticals Limited
Unit 5 Faraday Court
First Avenue, Centrum 100
Burton upon Trent
Staffordshire
DE14 2WX
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20046/0095
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 23 August 1996.
10
DATE OF REVISION OF THE TEXT
02/07/2015