IPRAVENT Rotacaps (Ipratropium bromide)

Transcription

1 Published on: 10 Jul 2014 IPRAVENT Rotacaps (Ipratropium bromide) Composition IPRAVENT Rotacaps Each capsule contains: Ipratropium Bromide BP, equivalent to Ipratropium Bromide (anhydrous) 40 mcg Excipient..q.s. Dosage Form Dry powder for inhalation Pharmacology Pharmacodynamics Ipratropium bromide is a quaternary ammonium derivative of atropine 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 Ca ++ caused by the interaction of acetylcholine with the muscarinic receptors 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 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. Pharmacokinetics Absorption The therapeutic effect of ipratropium 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 the lungs, depending on the formulation, device and inhalation technique. The major part of the dose is swallowed and passes through the gastro-intestinal tract. The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes). Cumulative renal excretion (0-24 hours) of 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 contribute significantly to systemic

2 exposure. Distribution The drug is minimally (less than 20%) bound to plasma proteins. Non-clinical data indicate that the quaternary amine of the ipratropium ion does not cross the placental or the blood-brain barrier. Biotransformation After intravenous administration approximately 60% of the dose is metabolised, mainly by conjugation (40%), whereas after inhalation about 77% of the systemically available dose is metabolised by ester hydrolysis (41%) and conjugation (36%). 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 Ipratropium has a mean 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 3.2 hours. Indications IPRAVENT Rotacaps are indicated for the treatment of chronic reversible airways obstruction, particularly in chronic bronchitis and asthma. Dosage And Administration IPRAVENT Rotacaps should only be used for inhalation through the Cipla Rotahaler/Revolizer. Adults (and Children >12 years) 1 or 2 rotacaps, three or four times daily. Children 6-12 years of age: 1 or 2 rotacaps three times daily. Below 6 years of age: 1 rotacap three times daily The recommended dose should not be exceeded. If therapy does not produce a significant improvement, if the patient's condition gets worse or if a reduced response to treatment becomes apparent, medical advice must be sought. The patient should be instructed that in the case of acute or rapidly worsening dyspnea a physician should be consulted immediately. 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.

3 Warnings And Precautions Drug Interactions Ipratropium has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, and steroids, commonly used in the treatment of chronic obstructive pulmonary disease. 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 The chronic co-administration of ipratropium bromide with other anticholinergic drugs has not been studied. Therefore, ipratropium bromide should not be administered concomitantly with other medications that contain a short- or longacting muscarinic antagonist (e.g. ipratropium, tiotropium, glycopyrronium, aclidinium, umeclidinium). Xanthine derivatives and beta 2 adrenergic agents may enhance the effect of ipratropium bromide. General Ipratropium is a bronchodilator for the maintenance treatment of bronchospasm associated with COPD and asthma and is not indicated for the initial treatment of acute episodes of bronchospasm where rescue therapy is required for rapid response. Patients must be instructed in the correct administration of IPRAVENT Rotacaps and care must be taken not to allow the powder to enter into 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 of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately. Patients should be informed when starting treatment that the onset of action of ipratropium bromide is slower than that of inhaled sympathomimetic bronchodilators. Excessive Use and Use with other Muscarinic Antagonists Ipratropium should not be used more frequently or at higher doses than recommended. Ipratropium should not be administered concomitantly with other medications that contain a short- or long-acting muscarinic antagonist (e.g. ipratropium, tiotropium, glycopyrronium, aclidinium, umeclidinium). Anticholinergic Effects Ocular Complications Caution is advocated in the use of anticholinergic agents in patients predisposed to or with 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 beta 2 - agonist, has come into contact with the eyes. Antiglaucoma therapy is effective in the prevention of acute narrow-angle glaucoma in susceptible individuals and patients who may be susceptible to glaucoma should be warned specifically on the need for ocular protection. Eye pain or discomfort, blurred vision, visual halos or coloured images in association with red eyes from conjunctival congestion and corneal edema 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 should be informed when starting treatment that the onset of action of ipratropium bromide is slower than that of inhaled sympathomimetic bronchodilators. Renal and Urinary Effects

4 Caution is advocated in the use of anticholinergic agents with pre-existing urinary outflow tract obstruction (e.g. prostatic hyperplasia or bladder-outflow obstruction). Hypersensitivity Immediate hypersensitivity reactions following the use of ipratropium have been demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal edema and anaphylaxis. In clinical trials and post marketing experience with ipratropium containing products, hypersensitivity reactions such as skin rash, pruritus, angioedema of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported. If such a reaction occurs, therapy with ipratropium bromide should be stopped at once and alternative treatment should be considered. Gastrointestinal 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. Paradoxical Bronchospasm Ipratropium can produce paradoxical bronchospasm that can be life threatening. If this occurs, treatment with ipratropium bromide should be stopped and the patient should be treated straight away with a fast acting inhaled bronchodilator. Dyspnea The patient should be instructed to consult a doctor immediately in the event of acute, rapidly worsening dyspnea. In addition, the patient should be warned to seek medical advice should a reduced response become apparent. Cardiovascular Cardiovascular effects, such as cardiac arrhythmias (e.g. atrial fibrillation and tachycardia), may be seen after the administration of muscarinic receptor antagonists. Pregnancy No adequate or well-controlled studies have been conducted in pregnant women. Nonclinical studies with ipratropium bromide have shown no embryotoxic or teratogenic effects following inhalation or intranasal application at doses considerably higher than those recommended in man. 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. The benefits of ipratropium bromide use during lactation should therefore be weighed against possible effects on the infant. Pediatrics The efficacy and safety in children and adolescents under 18 years has not been established. Ipratropium bromide is not indicated for pediatric patients. Effects on Ability to Drive and Use Machines No studies on the effects on the ability to drive and use machines have been performed.

5 However, patients should be advised that they may experience undesirable effects such as dizziness, accommodation disorder, mydriasis and blurred vision during treatment with ipratropium bromide. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery. Undesirable Effects Clinical Experience The following side effects have been reported. The frequencies given below are based on clinical trials involving patients who have been treated with ipratropium bromide. Frequencies Very common 1/10 1/100 < 1/10 1/1,000< 1/100 Rare 1/10,000 < 1/1,000 Very rare < 1/10,000 Immune system disorders Hypersensitivity Anaphylactic reaction Angioedema of tongue, lips, face Nervous system disorders Headache Dizziness Eye disorders Blurred vision

6 Glaucoma (1) Intraocular pressure increased (1) Eye pain (1) Mydriasis (1) Halo vision Conjunctival hyperemia Corneal oedema Accommodation disorder Rare Cardiac Disorders Increased heart rate Palpitations Supraventricular tachycardia Atrial fibrillation Rare Rare Respiratory, Thoracic and Mediastinal Disorders Cough Pharyngeal oedema Dry throat Bronchospasm Throat irritation Paradoxical bronchospasm (2) Laryngospasm Gastrointestinal Disorders Dryness of mouth Vomiting Gastro-intestinal motility disorder e.g. Diarrhoea Constipation Nausea Stomatitis

7 Skin and Subcutaneous Disorders Skin rash Pruritus Urticaria Rare Renal and Urinary Disorders Urinary retention (3) (1) Ocular complications have been reported when aerolised ipratropium bromide, either alone or in combination with an adrenergic beta 2 -agonist, has come into contact with the eyes during nebulizer therapy. (2) 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 Rotacaps should be discontinued immediately, the patient assessed and, if necessary, alternative treatment instituted. (3) The risk of urinary retention may be increased in patients with pre-existing urinary outflow tract obstruction. Other adverse events reported during various clinical trials include: Respiratory system disorders: Rhinitis, bronchitis, dyspnea, chronic obstructive airway disease, upper respiratory tract infection, pharyngitis, asthma, sinusitis Body as a whole: Pain, influenza like symptoms, back pain, chest pain, fatigue Gastrointestinal disorders: dyspepsia Central and peripheral nervous system disorders: dysphonia Special senses, other disorder: taste perversion Urinary system disorders: Urinary tract infection Musculoskeletal disorders: Myalgia Eye disorders: Conjunctivitis Postmarketing Experience World-wide safety data, including post-marketing data, spontaneous reports, literature reports, and reports from clinical trials list below the most frequent undesirable effects of ipratropium bromide according to system organ class. Immune system disorders: Hypersensitivity, anaphylactic reaction Nervous system disorders: headache, dizziness Eye disorders: vision blurred, mydriasis, intraocular pressure increased, glaucoma, eye pain, halo vision, conjunctival hyperemia. corneal edema, accommodation disorder Cardiac disorders: Palpitations, supraventricular tachycardia, atrial fibrillation, heart rate increased Respiratory, thoracic and mediastinal disorders: Throat irritation, cough, bronchospasm, bronchospasm paradoxical, laryngospasm, pharyngeal edema, dry throat Gastrointestinal disorders: dry mouth, nausea, gastrointestinal motility disorder, diarrhea, constipation, vomiting, stomatitis, edema mouth

8 Skin and subcutaneous tissue disorders: Rash, pruritus, angioedema, urticaria Renal and urinary disorders: Urinary retention If you experience any side-effects, talk to your doctor or pharmacist or write to You can also report side effects directly via the national pharmacovigilance program of India by calling on (Cipla Number) or you can report to PvPI on By reporting side-effects, you can help provide more information on the safety of this product. Overdosage Doses of ipratropium bromide up to 1.2 mg (60 puffs) have been administered by inhalation without the appearance of serious systemic anticholinergic effects. Minor systemic manifestations of anticholinergic action, including dry mouth, visual accommodation disorder and increase of heart rate may occur. Should signs of serious anticholinergic toxicity appear, cholinesterase inhibitors may be considered. Storage And Handling Instructions Keep the container tightly closed Store below 25 o C Protect from heat and moisture Packaging Information IPRAVENT Rotacaps.Sales pack contains 30 capsules Last Updated: December 2018 Last Reviewed: March 2019 IPRAVENT Rotacaps Source URL: