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Product
Anti-asthmatic Products (Budeflam Inhaler)
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Anti-asthmatic Products (Budeflam Inhaler)
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Ipravent Inhaler
Ipratropium Bromide Inhaler
COMPOSITION
Each actuation delivers:
Ipratropium Bromide ….. 20 mcg
(Appropriate overages added)
Suspended in propellant HFA 134a……………………q.s. udesonide BP…………..100 mcg
Budesonide BP…………..200 mcg
DOSAGE FORM
Inhalation Aerosol.
PHARMACOLOGY
Pharmacodynamics
BIpratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In pre-clinical 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 cyclic guanosine monophosphate (cyclic GMP) caused by the interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle.
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The bronchodilation following inhalation of ipratropium bromide is induced by local drug concentrations, sufficient for anticholinergic efficacy at the bronchial smooth muscle, and not by systemic drug concentrations.
In clinical trials using metered-dose inhalers in patients with reversible bronchospasm associated with asthma or COPD, significant improvements in pulmonary function (FEV 1 increases of 15% or more) occurred within 15 minutes, reached a peak in 1–2 hours, and persisted for approximately 4 hours.
Pre-clinical and clinical evidence suggest no deleterious effect of ipratropium bromide on airway mucous secretion, mucociliary clearance, or gas exchange.
Pharmacokinetics
The therapeutic effect of ipratropium bromide is produced by local action in the airways. Therefore, time courses of bronchodilation and systemic pharmacokinetics do not run in parallel.
Following inhalation, dose portions from 10–30%, depending on the formulation, device and inhalation technique, are generally deposited in the lungs. The major part of the dose is swallowed and passes through the gastrointestinal tract.
Due to the negligible gastrointestinal absorption of ipratropium bromide, the bioavailability of the swallowed dose portion is only approximately 2%. This fraction of the dose does not make a relevant contribution to the plasma concentrations of the active ingredient. The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes).
Limited data on total systemic bioavailability (pulmonary and gastrointestinal portions), based on renal excretion (0–24 hours) of ipratropium bromide, suggests a range of 7–28% when delivery is via a nebulizer or a metered-dose inhaler product. It is assumed that this is also a valid range for inhalation from the powder preparation. This is also a valid range for inhalation from the metered aerosol with HFA 134a propellant because the kinetic results (renal excretion, AUC and C max ) from the HFA formulation and the conventional CFC formulation are closely comparable.
Kinetic parameters describing the distribution of ipratropium bromide were calculated from plasma concentrations after intravenous administration. A rapid biphasic decline in plasma concentrations is observed. The volume of distribution (V beta ) 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 receptors 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. A study with radiolabelled material showed that approximately 10% of orally administered ipratropium bromide was absorbed from the gastrointestinal tract and metabolized. Less than 1% of an oral dose is renally excreted as the parent compound.
In excretion balance studies, after intravenous administration of a radioactive dose, less than 10% of the drug-related radioactivity (including the parent compound and all metabolites) is excreted via the biliary-faecal route. The dominant excretion of drug-related radioactivity occurs via the kidneys.
Trials (involving adult asthmatics, chronic obstructive pulmonary disease (COPD) patients and asthmatic children, and with treatment duration of up to 3 months) in which the HFA formulation and the CFC formulation have been compared have shown the two formulations to be therapeutically equivalent.
INDICATIONS
For the treatment of chronic reversible airways obstruction, particularly in chronic bronchitis and asthma.
DOSAGE AND ADMINISTRATION
Adults (Including the Elderly)
Usually 1 or 2 puffs, three or four times daily, although some patients may need up to
4 puffs at a time to obtain maximum benefit during early treatment.
Children
6–12 years
Usually 1 or 2 puffs, three times daily.
Below 6 Years
Usually 1 puff, three times daily.
The recommended dose should not be exceeded.
CONTRAINDICATIONS
Hypersensitivity to atropine or its derivatives, or to any component of the product.
Hypersensitivity to soya lecithin or related food products such as soya beans or peanuts.
WARNINGS AND PRECAUTIONS
Ipratropium bromide is not indicated for the initial treatment of acute episodes of bronchospasm where rapid response is required. Generally, caution is advocated in the use of anticholinergic agents in patients with glaucoma, prostatic hypertrophy, and bladder-neck obstruction.
Patients should be cautioned to avoid getting the inhaler spray into their eyes. This may result in precipitation or worsening of narrow-angle glaucoma, eye pain or discomfort, temporary blurring of vision, and visual halos or coloured images in association with red eyes from conjunctival congestion and corneal oedema. In such cases, patients should stop treatment with IPRAVENT Inhaler and start treatment with mitotic drops.
Drug Interactions
Ipratropium has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, and steroids, commonly used in the treatment of COPD. With the exception of salbutamol, there are no formal studies fully evaluating the interaction effects of ipratropium and these drugs with respect to effectiveness.
Anticholinergic Agents: Although ipratropium bromide is minimally absorbed into the systemic circulation, there is some potential for an additive interaction with concomitantly used anticholinergic medications. Caution is therefore advised in the co-administration of IPRAVENT Inhaler with other anticholinergic-containing drugs.
Pregnancy
Pregnancy Category B. No adequate or well-controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, ipratropium bromide should be used during pregnancy only if clearly needed.
Lactation
It is not known whether ipratropium bromide is excreted in human milk. Although lipid-insoluble quaternary bases pass into breast milk, it is unlikely that the active component, ipratropium bromide, would reach the infant to an important extent, especially when taken in aerosol form. However, because many drugs are excreted in human milk, caution should be exercised when ipratropium bromide is administered to a nursing mother.
UNDESIRABLE EFFECTS
The most frequent side effects seen are headache, nausea, and dryness of the mouth. Anticholinergic side effects, such as tachycardia and palpitations, visual accommodation disturbances, gastrointestinal motility disturbances, and urinary retention are rare and reversible.
OVERDOSAGE
Acute overdosage by inhalation is unlikely since ipratropium bromide is not well absorbed systemically after inhalation or oral administration.
PACKAGING INFORMATION
IPRAVENT Inhaler
Sales pack is available in a canister containing 200 metered doses.
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