INFORMATION FOR HEALTH PROFESSIONALS
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ATROVENT NASAL AQUEOUS is an aqueous isotonic, pH-adjusted (pH 4.0 - 5.0) solution for nasal administration. It contains 0.03% (300 mcg/ml) ipratropium bromide.
ATROVENT NASAL AQUEOUS is supplied in pump-activated, metered dose containers of 15 ml (180 metered doses) and 30 ml (380 metered doses). Each valve actuation delivers 70 microlitres of the solution, equivalent to 21 mcg ipratropium bromide.
ATROVENT NASAL AQUEOUS is a topical anticholinergic preparation. It contains ipratropium bromide, a synthetic quaternary ammonium derivative of atropine. Ipratropium bromide administered intranasally has a localised parasympathetic blocking action, which reduces watery hypersecretion from mucosal glands in the nose.
Nasal provocation trials in perennial rhinitis patients using ATROVENT NASAL AQUEOUS showed a dose-dependent increase in inhibition of methacholine-induced nasal secretion with an onset of action within 15 minutes. The duration of action of ATROVENT NASAL AQUEOUS was also dose-dependent.
Controlled clinical trials showed that intranasal ipratropium bromide is effective for controlling the severity and duration of rhinorrhoea in patients with allergic and non-allergic perennial rhinitis or the common cold.
Ipratropium bromide administration via nasal aerosol had no marked effect on sense of smell, nasal mucociliary transport, ciliary beat frequency, or the air-conditioning capacity of the nose.
Ipratropium bromide is a quarternary amine that is rapidly absorbed from the nasal mucosa, however to a low extent. In normal volunteers, in patients with an experimentally-induced cold or in perennial rhinitis patients less than 10% of a nasally given dose (single or multiple administration) is absorbed, as estimated from the renal excretion of ipratropium bromide over 24 hours. This corresponds to a systemic bioavailability of less than 20% (range: 7-18%).
The systemic absorption of ipratropium bromide across inflamed nasal mucosa due to experimentally-induced cold was not altered. After a single dose or QID dosing 6-8% of ipratropium bromide was excreted unchanged in healthy as well as in infected volunteers. Following chronic dosing in rhinitis patients the amount of unchanged ipratropium bromide excreted in the urine over a 24-hour period at steady state was 4-6% of the dose.
Kinetic parameters describing the disposition of ipratropium bromide were calculated from plasma concentrations after i.v. administration.
A rapid biphasic decline in plasma concentrations is observed. The volume of distribution (Vz) is 338 l (≈ 4.6 l/kg). The drug is minimally (less then 20%) bound to plasma proteins. The ipratropium ion does not cross the blood-brain barrier, consistent with the ammonium structure of the molecule.
The half-life of the terminal elimination phase is about 1.6 hours.
The mean total clearance of the drug is determined to be 2.3 L/min. The major portion of approximately 60% of the systemic available dose is eliminated by metabolic degradation, probably in the liver. The main urinary metabolites bind poorly to the muscarinic receptor and have to be regarded as ineffective.
A portion of approximately 40% of the systemic 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 gastro-intestinal 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.
ATROVENT NASAL AQUEOUS is indicated for the treatment and management of perennial rhinitis, allergic rhinitis and vasomotor rhinitis when characterised by watery rhinorrhoea.
ATROVENT NASAL AQUEOUS is also indicated for the symptomatic relief of rhinorrhoea associated with the common cold.
Priming of pump is required before first use.
| Adults: | Two puffs doses up each nostril 2 - 3 times a day. Some patients may need 3 - 4 puffs up each nostril during early therapy to obtain maximum benefit during early treatment. |
| Children: | 2 puffs up each nostril 2 times a day. |
Patients with occasional episodes of watery rhinorrhoea triggered by provocating factors, e.g. temperature changes, food and exercise, should administer 2 - 4 puffs up each nostril prior to exposure.
| Adults: | Initially: Two puffs into each nostril 3 - 4 times a day, followed by TWO further puffs five minutes after the first puffs. |
Known hypersensitivity to atropine or its derivatives, or to any of the ingredients of ATROVENT NASAL AQUEOUS (sodium chloride, benzalkonium chloride, disodium edetate dihydrate).
ATROVENT should be used with caution in patients predisposed to narrow-angle glaucoma, or with prostatic hyperplasia or bladder neck obstruction.
Patients with cystic fibrosis may be more prone to gastro-intestinal motility disturbances.
Immediate hypersensitivity reactions may occur after administration of ATROVENT, as demonstrated by rare cases of urticaria, angio-oedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
There have been isolated reports of ocular complications (i.e. mydriasis, increased intraocular 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. Thus patients must be instructed in the correct administration of ATROVENT NASAL AQUEOUS.
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 should be sought immediately.
The safety of ATROVENT during pregnancy has not been established. The benefits of using ATROVENT during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child. Preclinical studies showed no embryotoxic or teratogenic effects following inhalation at doses considerably higher than those recommended in man.
It is not known whether ipratropium bromide is excreted into human milk. Although lipid-insoluble quaternary cations pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to an important extent, when taken intranasally. However, because many drugs are excreted into human milk, caution should be exercised when ATROVENT is administered to nursing mothers.
Presumed to be safe or unlikely to produce an effect on the ability to drive or use machinery.
The most frequent local undesirable effects of ATROVENT NASAL AQUEOUS are nasal reactions including epistaxis, dryness of the nose and nasal irritation.
Headache, nausea and local irritation (e.g. burning sensation) may occur as non-specific reactions in association with use of ATROVENT NASAL AQUEOUS.
Potential systemic anticholinergic effects are dry mouth and dry throat. Ocular side effects, increase of heart rate and palpitations, urinary retention and gastrointestinal motility disturbances have been reported in isolated patients in association with use of ipratropium bromide either intranasally or after oral inhalation.
Allergic-type reactions such as skin rash, angio-oedema of tongue, lips and face, urticaria, laryngospasm and anaphylactic reactions may occur.
After oral inhalation of ipratropium bromide in patients suffering from COPD/Asthma supraventricular tachycardia and atrial fibrillation have been reported.
There is no evidence that the concomitant use of ATROVENT NASAL AQUEOUS with other drugs commonly prescribed for common cold i.e. decongestants increases the incidence of side effects.
ATROVENT NASAL AQUEOUS is minimally absorbed into the systemic circulation; nonetheless, there is some potential for additive interaction with other concomitantly administered anti-cholinergic medications, including ipratropium bromide containing aerosols for oral inhalation.
No symptoms specific to overdose have been encountered. In view of the wide therapeutic range and topical administration of ATROVENT, no serious anticholinergic symptoms are to be expected. Minor systemic manifestation of anticholinergic action, including dry mouth, visual accommodation disturbances and increase of heart rate may occur.
Store in a safe place out of the reach of children.
Store below 25°C. Avoid freezing.
Pharmacy Medicine
15ml pump-activated, metered dose container.
Priming of pump is required before first use.
ATROVENT® is a registered trademark.
Excipients
Sodium chloride, benzalkonium chloride, disodium edetate dihydrate.
If ATROVENT NASAL AQUEOUS is accidentally sprayed into the eyes, immediately flush the eyes with cool tap water.
If the nasal tip becomes clogged, remove the protective cap. Hold the nasal tip under running, warm tap water for about a minute. Dry the nasal tip, activate the nasal spray pump and replace the protective cap.
Neither active anaphylaxis nor passive cutaneous anaphylactic reactions were demonstrated in guinea pigs.
In vitro bacterial mutagenicity assays (Ames test) did not indicate a mutagenic potential. The results of in vivo assays (micronucleus test, dominant lethal test in mice, cytogenic assay on bone marrow cells of Chinese hamsters) did not demonstrate an increase in the rate of chromosomal aberrations.
No tumorigenic or carcinogenic effects were demonstrated in long term studies in mice and rats.
Studies to investigate the possible influence of ATROVENT on fertility, embryo-fetotoxicity, and peri-/postnatal development have been performed on mice, rats and rabbits. Even the highest oral dose levels employed (1000 mg/kg/day in the rat and 125 mg/kg/day in the rabbit, which proved to be maternotoxic and, to some extent, embryo-/fetotoxic at dosages, far in excess to the human therapeutic dose, did not induce malformations in the offspring.
BPI 0205-04 dated 30 May 2003
Boehringer Ingelheim (N.Z.) Limited
P O Box 76-216
Manukau City
AUCKLAND
NEW ZEALAND
Telephone: (09) 262-1356
Facsimile: (09) 262-1462
19 November 2003