Atrovent N

Atrovent N

ipratropium bromide

Manufacturer:

Boehringer Ingelheim

Distributor:

DKSH
Full Prescribing Info
Contents
Ipratropium bromide.
Description
Each metered dose (puff) contains ipratropium bromide 21 mcg corresponding to anhydrous ipratropium bromide 20 mcg.
Ipratropium bromide is (8r)-3α-hydroxy-8-isopropyl-1αH,5αH-tropanium bromide (±)-tropate monohydrate.
It also contains the following excipients: Propellant: 1,1,1,2-tetrafluoroethane [hydrofluoroalkane (HFA) 134a].
Other Excipients: Anhydrous citric acid, anhydrous ethanol, nitrogen (inert gas) and purified water.
Action
Pharmacology: Atrovent N is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In preclinical studies, it appears to inhibit vagally mediated reflexes by antagonising the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of calcium ion which is caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.
Calcium ion release is mediated by the second messenger system consisting of inositol triphosphate (IP3) and diacylglycerol (DAG).
The bronchodilation following inhalation of Atrovent N is primarily local and site specific to the lungs, and not systemic in nature.
Preclinical and clinical evidence suggest no deleterious effect of Atrovent N on airway mucous secretion, mucociliary clearance or gas exchange.
Trials with a treatment duration of up to 3 months involving adult asthmatics and chronic obstructive pulmonary disease (COPD) patients, and asthmatic children, in which the HFA formulation and the chlorofluorocarbon (CFC) formulation have been compared have shown the 2 formulations to be therapeutically equivalent.
In controlled 90-day studies in patients with bronchospasm associated with COPD (chronic bronchitis and emphysema), significant improvements in pulmonary function occurred within 15 min, reached a peak in 1-2 hrs and persisted in the majority of patients for up to 4-6 hrs.
In controlled 90-day studies in patients with bronchospasm associated with asthma, significant improvements in pulmonary function (FEV1 increases of 15%) occurred in 54% of the patients.
Pharmacokinetics: The therapeutic effect of Atrovent N is produced by a local action in the airways. Time courses of bronchodilation and systemic pharmacokinetics do not run in parallel.
Following inhalation, 10-30% of a dose is generally deposited in lungs, depending on the formulation and inhalation technique. The major part of the dose is swallowed and passes the gastrointestinal tract.
The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes). Cumulative renal excretion (0-24 hrs) of parent compund is approximated to 46% of an IV administered dose, below 1% of an oral dose and approximately 3-13% of an inhaled dose. Based on these data, the total systemic bioavailability of oral and inhaled doses of ipratropium bromide is estimated at 2% and 7-28%, respectively.
Taking this into account, swallowed dose portions of ipratropium bromide do not relevantly contribute to systemic exposure.
After inhalation of ipratropium bromide either with HFA 134a or CFC propellant, cumulative renal excretion over 24 hrs was approximately 12% and 10%, respectively.
Kinetic parameters describing the disposition of ipratropium were calculated from plasma concentrations after IV administration. A rapid biphasic decline in plasma concentrations is observed. The apparent volume of distribution at steady state (Vdss) is approximately 176 L (≈2.4 L/kg). The drug is minimally (<20%) bound to plasma proteins. The quaternary amine ipratropium does not cross the blood-brain barrier.
The half-life of the terminal elimination phase is approximately 1.6 hrs.
Ipratropium has a total clearance of 2.3 L/min and a renal clearance of 0.9 L/min. After IV administration, approximately 60% of a dose is metabolised, probably the major portion in the liver by oxidation.
In an excretion balance study, cumulative renal excretion (6 days) of drug-related radioactivity (including parent compound and all metabolites) accounted for 72.1% after IV administration, 9.3% after oral administration and 3.2% after inhalation. Total radioactivity excreted via the faeces was 6.3% following IV application, 88.5% following oral dosing and 69.4% after inhalation. Regarding the excretion of drug-related radioactivity after IV administration, the main excretion occurs via the kidneys. The half-life for elimination of drug-related radioactivity (parent compound and metabolites) is 3.6 hrs. The main urinary metabolites bind poorly to the muscarinic receptor and have to be regarded as ineffective.
Indications/Uses
Bronchodilator for maintenance treatment of bronchospasm associated with COPD including chronic bronchitis, emphysema and asthma.
Dosage/Direction for Use
The dosage should be adapted to the individual requirements; patients should be kept under medical supervision during treatment. It is advisable not to exceed the recommended daily dose during either acute or maintenance treatment.
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 physician should be consulted immediately.
Unless otherwise prescribed, the following dosages are recommended: Adults and Children >6 years: 2 metered doses (puffs) 4 times daily.
Since a requirement for increasing doses suggests that additional therapeutic modalities may be needed, a total daily dose of 12 puffs should generally not be exceeded.
For acute exacerbations of COPD, treatment with Atrovent inhalation solution or unit-dose vials may be indicated.
Because of insufficient information in children, Atrovent N metered aerosol should only be used on medical advice and under the supervision of an adult.
Overdosage
No symptoms specific to overdose have been encountered. In view of the wide therapeutic range and topical administration of Atrovent N, no serious anticholinergic symptoms are to be expected. Minor systemic manifestations of anticholinergic action, including dry mouth, visual accommodation disturbances and increase of heart rate may occur.
Contraindications
Known hypersensitivity to atropine or its derivatives, or to any other components of Atrovent N.
Warnings
The plastic mouthpiece has been specially designed for use with Atrovent N metered dose aerosol to ensure that the patient always gets the right amount of the medicine. The mouthpiece must never be used with any other metered aerosol nor must the Atrovent N metered dose aerosol be used with any mouthpiece other than the one supplied with the product.
The container is under pressure and should by no account be opened by force or exposed to temperatures above 50°C.
Special Precautions
When using the new formulation of Atrovent N for the first time, some patients may notice that the taste is slightly different from that of the chlorofluorocarbon (CFC)-containing formulation. Patients should be made aware of this when changing from one formulation to the other. They should also be told that the formulations have been shown to be interchangeable for all practical purposes, and that the difference in taste has no consequences in terms of the safety or the efficacy of the new formulation.
Immediate hypersensitivity reactions may occur after administration of Atrovent N, as demonstrated by rare cases of rash, urticaria, angioedema, oropharyngeal oedema, bronchospasm and anaphylaxis.
Atrovent N should be used with caution in patients predisposed to narrow angle glaucoma, or with preexisting urinary outflow tract obstruction (eg, prostatic hyperplasia or bladder-neck obstruction).
Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.
Ocular Complications: There have been isolated reports of ocular complications (ie, mydriasis, increased intraocular pressure, narrow angle glaucoma, eye pain) when aerosolised ipratropium bromide either alone or in combination with an adrenergic β2-agonist, has come in contact with the eyes. Thus, patients must be instructed in the correct administration of Atrovent N metered aerosol.
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.
Care must be taken not to allow the mist to enter into the eyes. Since the metered dose aerosol is applied via mouthpiece and manually controlled, the risk for the mist entering the eyes is limited.
Effects on the Ability to Drive or Operate Machinery: 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 eg, dizziness, accomodation disorder, mydriasis and blurred vision during treatment with Atrovent N. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience the previously mentioned side effects, they should avoid potentially hazardous tasks eg, driving or operating machinery.
Fertility: Clinical data on fertility are no available for ipratropium bromide.
Use in pregnancy & lactation: The safety of Atrovent N during human pregnancy has not been established. The benefits of using Atrovent N during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child. Preclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application, at doses considerably higher than those recommended in man.
It is not known whether Atrovent N is excreted into breast milk. Although lipid-insoluble quaternary cations pass into breast milk, it is unlikely that Atrovent N would reach the infant to an important extent, when administered by inhalation. However, because many drugs are excreted into breast milk, caution should be exercised when Atrovent N is administered to nursing mothers.
Use In Pregnancy & Lactation
The safety of Atrovent N during human pregnancy has not been established. The benefits of using Atrovent N during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child. Preclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application, at doses considerably higher than those recommended in man.
It is not known whether Atrovent N is excreted into breast milk. Although lipid-insoluble quaternary cations pass into breast milk, it is unlikely that Atrovent N would reach the infant to an important extent, when administered by inhalation. However, because many drugs are excreted into breast milk, caution should be exercised when Atrovent N is administered to nursing mothers.
Side Effects
Many of the listed undesirable effects can be assigned to the anticholinergic properties of Atrovent N. As with all inhalation therapy, Atrovent N may show symptoms of local irritation. Adverse drug reactions were identified from data obtained in clinical trials and pharmacovigilance during post approval use of Atrovent N.
The most frequent side effects reported in clinical trials were headache, throat irritation, cough, dry mouth, gastrointestinal motility disorders (including constipation, diarrhoea and vomiting), nausea and dizziness.
Immune System Disorders: Hypersensitivity, anaphylactic reaction.
Nervous System Disorders: Headache, dizziness.
Eye Disorders: Blurred vision, mydriasis, increased intraocular pressure, glaucoma, eye pain, halo vision, conjunctival hyperaemia, corneal oedema, accomodation disorder.
Cardiac Disorders: Palpitations, supraventricular tachycardia, atrial fibrillation, increased heart rate.
Respiratory, Thoracic and Mediastinal Disorders: Throat irritation, cough, bronchospasm, paradoxical bronchospasm, larnygospasm, pharyngeal oedema, dry throat.
Gastrointestinal Disorders: Dry mouth, nausea, gastrointestinal motility disorder, diarrhoea, constipation, vomiting, stomatitis, mouth oedema.
Skin and Subcutaneous Tissue Disorders: Rash, pruritus, angioedema, urticaria.
Renal and Urinary Disorders: Urinary retention.
Drug Interactions
Beta-adrenergics and xanthine preparations may intensify the bronchodilatory effect.
Caution For Usage
Instructions for Use and Handling: The correct administration is essential for successful therapy.
Depress the valve twice before the inhaler is used for the first time.
Before each use the following rules should be observed: Remove protective cap.
Breathe out deeply.
Hold the inhaler and close lips over the mouthpiece. The arrow and the base of the container should be pointing upwards.
Breathe in as deeply as possible, pressing the base of the canister firmly at the same time, this releases 1 metered dose. Hold the breath for a few seconds, then remove the mouthpiece and breathe out. The same action should be repeated for a second inhalation.
Replace the protective cap after use.
After not using the inhaler for 3 days, the valve has to be actuated once.
The container is not transparent. It is not therefore possible to see when it is empty. The inhaler will deliver 200 doses. When these have all been used, the canister may still appear to contain a small amount of fluid. The inhaler should, however, be replaced because the patient may not get the right amount of treatment.
The amount of treatment in the inhaler can be checked as follows: Shaking the canister will show if there is any remaining fluid.
Alternatively remove the canister from the plastic mouthpiece and put it into a container of water. The contents of the canister can be estimated by observing its position in the water.
Clean the inhaler at least once a week. It is important to keep the mouthpiece of the inhaler clean to ensure that medicine does not build up and block the spray.
For cleaning, 1st take off the dust cap and remove the canister from the inhaler. Rinse warm water through the inhaler until no medication build up and/or dirt is visible.
After cleaning, shake out the inhaler and let it air-dry without using any heating system. Once the mouthpiece is dry, replace the canister and the dust cap.
Storage
Store below 30°C.
ATC Classification
R03BB01 - ipratropium bromide ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, anticholinergics.
Presentation/Packing
MDI (clear, colourless liquid, free from suspended particles) 20 mcg/dose x 200 doses/10 mL.
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