IPRAVENT Respules/Respirator solution (Ipratropium bromide)

Transcription

1 Published on: 19 Sep 2014 IPRAVENT Respules/Respirator solution (Ipratropium bromide) Composition IPRAVENT Respules Each 2 ml contains: Ipratropium Bromide BP equivalent to Ipratropium Bromide (anhydrous) 500mcg Isotonic solution q.s. IPRAVENT Respirator Solution Each 2 ml contains: Ipratropium Bromide BP 500 mcg Dosage Form Solution and respules for nebulization Description Ipratropium bromide (Synthetic quaternary ammonium compound) is an anticholinergic bronchodilator, chemically related to atropine. It is a white crystalline substance, freely soluble in water and lower alcohols, and insoluble in lipophilic solvents such as ether, chloroform, and fluorocarbons. Pharmacology Pharmacodynamics Ipratropium bromide is an anticholinergic with 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. 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. Pre-clinical and clinical evidence suggest no deleterious effect of ipratropium bromide on airway mucous secretion, mucociliary clearance, or gas exchange. The bronchodilator effect of ipratropium in the treatment of acute bronchospasm associated with asthma has been shown in studies in adults and children over 6 years of age. In most of these studies ipratropium was administered in combination with an inhaled beta 2 agonist. Pharmacokinetics

2 Absorption 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, suggest 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. 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. Distribution The volume of distribution (V z ) 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. Biotransformation 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. Elimination 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. 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. Indications IPRAVENT Respules/IPRAVENT Respirator Solution administered either alone or with other bronchodilators, especially beta-adrenergics, is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema. IPRAVENT Respules/IPRAVENT Respirator Solution are indicated, when used concomitantly with inhaled beta 2 -agonists, for treatment of reversible airways obstruction as in acute and chronic asthma. Dosage And Administration The respules/ respirator solution is intended only for inhalation with suitable nebulizing devices and should not be taken orally or administered parenterally. Adults (Including the Elderly) and Children (Over 12 Years of Age) mcg, three to four times daily For the Treatment of Acute Bronchospasm

3 250 mcg three to four times until the patient is stable. Daily doses exceeding 2 mg in adults and children over 12 years of age should only be given under medical supervision. Children (6 12 Years of Age) 250 mcg; up to a total daily dose of 1 mg Children (0 5 Years of Age) For the Treatment of Acute Asthma Only mcg; up to a total daily dose of 1 mg Ipratropium bromide should be administered no more frequently than 6-hourly in children less than 5 years of age. For acute bronchospasm, repeated doses may be administered until the patient is stable. Where co-administration is required, IPRAVENT Respules/IPRAVENT Respirator Solution may be combined with a short-acting, beta 2 -agonist in the same nebulizer chamber. The solution should be used as soon as possible after mixing and any unused solution should be discarded. Contraindications Ipratropium bromide is contraindicated in known or suspected cases of hypersensitivity to ipratropium bromide, or to atropine and its derivatives. Warnings And Precautions Use of the nebulizer solution should be subject to close medical supervision during initial dosing. Caution is advocated in the use of anticholinergic agents in patients predisposed to or with narrow-angle glaucoma, or with prostatic hyperplasia or bladder-outflow obstruction. As patients with cystic fibrosis may be prone to gastro-intestinal motility disturbances, ipratropium bromide, as with other anticholinergics, should be used with caution in these patients. Immediate hypersensitivity reactions following the use of ipratropium bromide have been demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis. There have been isolated reports of ocular complications (i.e. mydriasis, increased intra-ocular pressure, narrow-angle glaucoma, eye pain) when aerosolised ipratropium bromide, either alone or in combination with an adrenergic beta 2 - agonist, has come into contact with the eyes during nebulizer therapy. 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. Patients must be instructed in the correct administration of IPRAVENT Respules/IPRAVENT Respirator Solution. Care must be taken not to allow the solution or mist to enter the eyes. It is recommended that the nebulized solution is administered via a mouthpiece. If this is not available and a nebulizer mask is used, it must fit properly. Patients who may be predisposed to glaucoma should be warned specifically to protect their eyes. As with other inhalation therapy, inhalation induced bronchoconstriction may occur with an immediate increase in wheezing after dosing. This should be treated straight away with a fast-acting inhaled bronchodilator. IPRAVENT Respules/IPRAVENT Respirator Solution should be discontinued immediately, the patient assessed and, if necessary, alternative treatment instituted. Drug Interactions There is evidence that the administration of ipratropium with beta-adrenergic drugs and xanthine preparations may

4 produce an additive bronchodilatory effect. The risk of acute glaucoma in patients with a history of narrow-angle glaucoma may be increased when nebulised ipratropium bromide and beta 2 -agonists are administered simultaneously. 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 inhaled. However, because many drugs are excreted in human milk, caution should be exercised when ipratropium bromide is administered to a nursing mother. Undesirable Effects Many of the listed undesirable effects can be assigned to the anticholinergic properties of ipratropium. As with all inhalation therapy, IPRAVENT Respules/IPRAVENT Respirator Solution 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 common non-respiratory adverse reactions reported in clinical trials are headache, nausea (with or without vomiting) dryness of the mouth. The common adverse effects ( 1/100 < 1/10) include: nervous system disorders (headache), respiratory, thoracic and mediastinal disorders (cough, throat irritation), gastro-intestinal disorders [dryness of mouth, nausea and disturbances in gastrointestinal motility (diarrhoea, constipation, and vomiting). The uncommon adverse effects ( 1/1,000 < 1/100) include: immune system disorders (Urticaria), eye disorders Accommodation disturbances, narrow-angle glaucoma, cardiac disorders (Tachycardia), respiratory, thoracic and mediastinal disorders (spasm of the larynx), skin and subcutaneous disorders (Exanthema. The rare adverse effects ( 1/10,000 < 1/1000) seen include: immune system disorders (anaphylactic reaction, hypersensitivity, angioedema of tongue, lips & face), eye disorders (Increased intraocular pressure, pain in the eyes, mydriasis), cardiac disorders (Palpitations, supraventricular tachycardia, atrial fibrillation. Respiratory, thoracic and mediastinal disorders (Bronchospasms induced by the inhalation) the risk of urinary retention may be increased in patients with preexisting urinary outflow tract obstruction. If case of any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the National Pharmacovigilance Programme of India by calling on By reporting side effects, you can help provide more information on the safety of this product. Overdosage Palpitation and increase in heart rate have been produced with inhaled doses of 5 mg. Side effects have not been caused by single inhaled doses of 2 mg in adults and 1 mg in children. Single oral doses of 30 mg of ipratropium bromide caused anticholinergic side effects, but these did not require treatment. Severe overdose is characterized by atropine-like symptoms like tachycardia, tachypnea, high fever and central effects like restlessness, confusion and hallucinations. These symptoms should be treated symptomatically. The use of

5 physostigmine is not recommended because of worsening of cardiotoxic symptoms and induction of convulsions. Packaging Information IPRAVENT Respules 500mcg. available as respule of 2 ml IPRAVENT Respirator Solution 500mcg...Bottle of 15 ml Last Updated: July 2018 Last Reviewed: July 2018 IPRAVENT Respules/Respirator solution Source URL: