Atrovent定喘樂

Atrovent

ipratropium bromide

Manufacturer:

Boehringer Ingelheim

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Contents
Ipratropium bromide anhydrous.
Description
Metered Dose Inhaler: 1 metered dose (puff) contains 0.021 mg ipratropium bromide monohydrate corresponding to 0.020 mg ipratropium bromide anhydrous.
Solution for inhalation: 1 mL (20 drops) of 0.025% solution for inhalation with nebulising devices contains 261 mcg ipratropium bromide monohydrate corresponding to 250 mcg ipratropium bromide anhydrous.
Excipients/Inactive Ingredients: Solution for inhalation: Benzalkonium chloride, Disodium edetate dihydrate, Sodium chloride for parenteral administration, 1 N Hydrochloric acid, Purified water.
Action
Pharmacotherapeutic group: Anticholinergics. ATC Code: R03BB01.
Pharmacology: ATROVENT (ipratropium bromide) is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In nonclinical studies, it appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.
Ca++ release is mediated by the second messenger system consisting of IP3 (inositol triphosphate) and DAG (diacylglycerol).
The bronchodilation following inhalation of ATROVENT (ipratropium bromide) is primarily local and site specific to the lung and not systemic in nature.
Preclinical and clinical evidence suggest no deleterious effect of ATROVENT (ipratropium bromide) on airway mucous secretion, mucociliary clearance or gas exchange.
Clinical trials: Metered Dose Inhaler/Solution for inhalation: Trials with a treatment duration of up to three months involving adult asthmatics and COPD patients, and asthmatic children, in which the CFC-free formulation and the CFC formulation have been compared have shown the two formulations to be therapeutically equivalent.
In controlled 90 day studies in patients with bronchospasm associated with chronic obstructive pulmonary disease (chronic bronchitis and emphysema) significant improvements in pulmonary function occurred within 15 minutes, reached a peak in 1-2 hours, and persisted for up to 4 - 6 hours.
In controlled 90 day studies in patients with bronchospasm associated with asthma, significant improvements in pulmonary function (FEV1 increases of 15%) occurred in 51% of the patients.
Pharmacokinetics: Absorption: The therapeutic effect of ATROVENT is produced by a local action in the airways. Time courses of bronchodilation and systemic pharmacokinetics do not run in parallel.
Following inhalation 10 to 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 gastro-intestinal tract.
The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes).
Cumulative renal excretion (0-24 hrs) of the parent compound is approximated to 46% of an intravenously administered dose, below 1% of an oral dose and approximately 3 to 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 to 28%, respectively.
Taking this into account, swallowed dose portions of ipratropium bromide do not relevantly contribute to systemic exposure.
Distribution: Kinetic parameters describing the disposition of ipratropium were calculated from plasma concentrations after i.v. 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 (less than 20%) bound to plasma proteins. Nonclinical data indicate that quaternary amine ipratropium does not cross the placental or the blood-brain barrier.
Biotransformation: After intravenous administration approximately 60% of a dose is metabolised, the major portion probably in the liver by oxidation.
The known metabolites, which are formed by hydrolysis, dehydration or elimination of the hydroxy-methyl group in the tropic acid moiety, show very little or no affinity for the muscarinic receptor and have to be regarded as ineffective.
Elimination: The half-life of the terminal elimination phase is approximately 1.6 hours.
Ipratropium has a total clearance of 2.3 L/min and a renal clearance of 0.9 L/min.
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 intravenous administration, 9.3% after oral administration and 3.2% after inhalation. Total radioactivity excreted via the faeces was 6.3% following intravenous application, 88.5% following oral dosing and 69.4% after inhalation. Regarding the excretion of drug-related radioactivity after intravenous administration, the main excretion occurs via the kidneys. The half-life for elimination of drug-related radioactivity (parent compound and metabolites) is 3.6 hours.
Indications/Uses
Metered Dose Inhaler: ATROVENT metered dose inhaler is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis, emphysema and asthma.
Solution for inhalation: ATROVENT is indicated as a bronchodilator for the prevention and treatment of symptoms in chronic obstructive airway disorders with reversible bronchospasm such as bronchial asthma and especially chronic bronchitis with or without emphysema.
Dosage/Direction for Use
The dosage should be adapted to the individual requirements of the patients who 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. The patients should be instructed that in the case of acute or rapidly worsening dyspnoea a physician should be consulted immediately.
The following doses are recommended: Metered Dose Inhaler: Maintenance treatment: Adults and children > 6 years of age: 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 chronic obstructive pulmonary disease treatment with ATROVENT solution for inhalation may be indicated.
Because of insufficient information in children ATROVENT metered dose inhaler should only be used on medical advice and under the supervision of an adult.
Solution for inhalation: 20 drops = about 1 mL.
1 drop = 0.0125 mg ipratropium bromide anhydrous.
Adults (including elderly) and adolescents > 14 years of age: 0.4 - 2.0 mL (8 - 40 drops = 0.1 - 0.5 mg ipratropium bromide anhydrous) 3 - 4 times daily.
Children 6 - 14 years of age: 0.4 - 1.0 mL (8 - 20 drops = 0.1 - 0.25 mg ipratropium bromide anhydrous) 3 - 4 times daily.
Children < 6 years of age: Because there is limited information in this age group the following dose recommendation should be given under medical supervision: 0.4 - 1.0 mL (8 - 20 drops = 0.1 - 0.25 mg ipratropium bromide anhydrous) 3 - 4 times daily.
Overdosage
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 manifestations of anticholinergic action, including dry mouth, visual accommodation disorder and increase of heart rate may occur.
Contraindications
ATROVENT is contraindicated in patients with known hypersensitivity to atropine or its derivatives (such as the active substance ipratropium bromide) or to any other component of the product.
Special Precautions
Hypersensitivity: Immediate hypersensitivity reactions may occur after administration of ATROVENT, as demonstrated by rare cases of rash, urticaria, angioedema, oropharyngeal oedema, bronchospasm and anaphylaxis.
Paradoxical bronchospasm: As with other inhaled medicines ATROVENT may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs ATROVENT should be discontinued immediately and substituted with an alternative therapy.
Renal and urinary effects: ATROVENT should be used with caution in patients with micturition disorders (such as in prostatic hypertrophy or bladder neck obstruction), the benefit of treatment with ipratropium bromide must be carefully weighed against the potential risk of aggravating urinary retention.
Gastro-intestinal motility disturbances: Patients with cystic fibrosis may be more prone to gastro-intestinal motility disturbances.
Ocular complications: ATROVENT should be used with caution in patients predisposed to narrow-angle glaucoma. 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.
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.
Patients must be instructed in the correct administration of ATROVENT.
Metered Dose Inhaler: Care must be taken not to allow the mist to enter into the eyes. Since the metered dose aerosol is applied via mouth piece and manually controlled, the risk for the mist entering the eyes is limited.
Solution for inhalation: Care must be taken not to allow the solution or mist to enter into the eyes. It is recommended that the nebulised solution be administered via a mouth piece. 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.
Local effects: Solution for inhalation: This product contains the preservative benzalkonium chloride and the stabiliser disodium edetate dihydrate. When inhaled these components may cause bronchospasm in sensitive patients with hyper reactive airways.
Effects on ability to drive and use machines: 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 such as dizziness, accommodation disorder, mydriasis and blurred vision during treatment with ATROVENT. Therefore, caution should be recommended when driving a car or operating machinery.
Use In Pregnancy & Lactation
Pregnancy: The safety of ATROVENT during human 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. Nonclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application at doses considerably higher than those recommended in man.
Lactation: It is not known whether ipratropium bromide is excreted into breast milk. But it is unlikely that ipratropium bromide would reach the infant to an important extent, especially when administered by inhalation. However, caution should be exercised when ATROVENT is administered to nursing mothers.
Fertility: Clinical data on fertility are not available for ipratropium bromide. Nonclinical studies performed with ipratropium bromide showed no adverse effect on fertility.
Side Effects
Many of the listed undesirable effects can be assigned to the anticholinergic properties of ATROVENT. As with all inhalation therapy ATROVENT may show symptoms of local irritation. Adverse drug reactions were identified from data obtained in clinical trials and pharmacovigilance during post approval use of the drug.
The most frequent side effects reported in clinical trials were headache, throat irritation, cough, dry mouth, gastro-intestinal motility disorders (including constipation, diarrhoea and vomiting), nausea and dizziness. (See table.)

Click on icon to see table/diagram/image

Common ≥ 1/100 - < 1/10; Uncommon ≥ 1/1,000 - < 1/100; Rare ≥ 1/10,000 - <1/1,000.
Drug Interactions
The chronic co-administration of ATROVENT inhalation with other anticholinergic drugs has not been studied. Therefore, the chronic co-administration of ATROVENT with other anticholinergic drugs is not recommended.
Beta-adrenergics and xanthine preparations may intensify the bronchodilator effect.
Solution for inhalation: The risk of acute glaucoma in patients with a history of narrow-angle glaucoma (see Precautions) may be increased when nebulised ipratropium bromide and beta-mimetics are administered simultaneously.
Caution For Usage
Instructions for use: Please read the instructions for use carefully, to ensure correct administration.
Metered Dose Inhaler: The correct administration is essential for successful therapy.
Before first time use: Depress the valve twice before the inhaler is used.
Before each use the following rules should be observed: 1. Remove protective cap.
2. Breathe out deeply.
3. Hold the inhaler, and close lips over the mouthpiece. The arrow and the base of the container should be pointing upwards.
4. Breathe in as deeply as possible, pressing the base of the canister firmly at the same time, this releases one 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.
5. Replace the protective cap after use.
6. After not using the inhaler for three days the valve has to be actuated once.
The container is not transparent. It is therefore not possible to see when it is empty. The inhaler will deliver 200 puffs. 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 you may not get the right amount of treatment.
The amount of treatment in your 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 your inhaler at least once a week.
It is important to keep the mouthpiece of your inhaler clean to ensure that medicine does not build up and block the spray.
For cleaning, first 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.
WARNING: The plastic mouthpiece has been specially designed for use with ATROVENT metered dose inhaler to ensure that you always get the right amount of the medicine. The mouthpiece must never be used with any other metered dose inhaler nor must the ATROVENT metered dose inhaler be used with any mouthpiece other that 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.
Solution for inhalation: The recommended dose is to be diluted with physiological saline to a final volume of 3 - 4 mL and nebulised and inhaled until the solution is consumed. The solution should be rediluted each time before use; any residual diluted solution should be discarded.
Dosage may be dependent upon the mode of inhalation and the quality of nebulisation. In the case of particle sizes up to 5 mcm or with assisted ventilation dose levels may be reduced to approximately 0.4 mL (8 drops = 0.1 mg). The duration of inhalation can be controlled by the dilution volume.
The dose may be repeated after intervals of at least 2 hours, if required.
Daily doses exceeding 2 mg (1 mg in children) should be given under medical supervision.
Patients should be advised to consult a doctor or the nearest hospital immediately in the case of acute or rapidly worsening dyspnea (difficulty in breathing) if additional inhalations do not produce an adequate improvement.
ATROVENT solution for inhalation can be administered using a range of commercially available nebulising devices. Where wall oxygen is available the solution is best administered at a flow rate of 6 - 8 litres per minute.
ATROVENT solution for inhalation and disodium cromoglycate inhalation solutions should not be administered simultaneously in the same nebuliser as precipitation may occur.
MIMS Class
Antiasthmatic & COPD Preparations
ATC Classification
R03BB01 - ipratropium bromide ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, anticholinergics.
Presentation/Packing
MDI (CFC-free) 20 mcg/puff x 200 puffs. Inhalation soln 0.025% x 20 mL.
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