Product Index

Composition

DUOLIN Inhaler

Each puff contains

Levosalbutamol Tartarate……50 mcg

Ipratropium Bromide………..20 mcg

Dosage Form

Inhalation aerosol

Description

DUOLIN Inhaler Is a combination of ipratropium bromide and levosalbutamol tartarate.

Ipratropium bromide is an anticholinergic (parasympatholytic) agent, which inhibits vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve.

Levosalbutamol tartarate is a relatively selective beta₂-adrenergic agonist, whose activation leads to an increase in intracellular adenyl cyclase, the enzyme which catalyses the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'- adenosine monophosphate (cAMP).

Pharmacology

Pharmacodynamics

Levosalbutamol

Activation of beta₂-adrenergic receptors on airways smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of cAMP. The increase in cAMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation. 

Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cAMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional antagonist to relax the airways, irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. While it is recognized that beta₂-adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta-receptors in the human heart, 10-50% of which are beta₂-adrenergic receptors. The precise function of these receptors has not been established. 

However, all beta-adrenergic agonist drugs can produce significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. 

Ipratropium Bromide

Ipratropium bromide is an anticholinergic (parasympatholytic) agent, which appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at neuromuscular junctions in the lungs. Anticholinergics prevent increases in intracellular concentration of cyclic guanosine monophosphate (cGMP), which are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. 

Pharmacokinetics 

No pharmacokinetic studies have been carried out on levosalbutamol tartarate and ipratropium bromide combination. Hence pharmacokinetics of levosalbutamol and ipratropium bromide has been discussed individually.

Levosalbutamol

A population pharmacokinetics model was developed using plasma concentrations of (R)-salbutamol obtained from 632 asthmatic patients, aged 4­ to 81 years, in three large trials. For adolescent and adult patients 12 years and older, following a 90 mcg dose of R salbutamol yielded a mean peak plasma concentrations (C_max) and systemic exposure (AUC_0-6) of approximately 199 pg/ml and 695 pg.h/ml, respectively, compared to approximately 238 pg/ml and 798 pg.h/ml, respectively, following 180 mcg dose of racemic salbutamol. For pediatric patients 4 to 11 years of age, following 90 mcg dose of R salbutamol, yielded C_max and AUC_0-6 of approximately 163 pg/ml and 579 pg.h/ml, respectively compared to approximately 238 pg/ml and 82 pg.h/ml, respectively, following 180 mcg dose of racemic salbutamol.

These pharmacokinetic data indicate that the mean exposure of (R)-salbutamol was 13-16% less in adults and 30%-32% less in pediatric patients as compared to those given a comparative dose of racemic salbutamol. When compared to adult patients, pediatric patients given 90 mcg of levosalbutamol have a 17% lower mean exposure to R salbutamol.

Information available in published literature suggests that the primary enzyme responsible for the metabolism of salbutamol enantiomers in humans is SULT1A3 (sulphotransferase). When racemic salbutamol was administered either intravenously or via inhalation after oral charcoal administration, there was a 3- to 4-fold difference in the area under the concentration time curves between the (R) - and (S)-salbutamol enantiomers, with (S)-salbutamol concentrations being consistently higher. However, without charcoal pre-treatment, after either oral or inhalation administration the differences were 8- to 24-fold, suggesting that (R)-salbutamol is preferentially metabolized in the gastrointestinal tract, presumably by SULT1A3. 

The primary route of elimination of salbutamol enantiomers is through renal excretion (80-100%) of either the parent compound or the primary metabolite. Less than 20% of the drug is detected in the feces. Following intravenous administration of racemic salbutamol, between 25% and 46% of the (R) ­-salbutamol fraction of the dose was excreted as unchanged (R)-salbutamol in the urine.

Special Populations

Renal Impairment

The effect of renal impairment on the pharmacokinetics of racemic salbutamol was evaluated in 5 subjects with creatinine clearance of 7-53 ml/min, and the results were compared with those from healthy volunteers. Renal disease had no effect on the half-life, but there was a 67% decline in racemic salbutamol clearance. Caution should be used when administering high doses of levosalbutamol Inhaler to patients with renal impairment. 

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of levosalbutamol inhaler has not been evaluated.

Ipratropium Bromide

The bronchodilation following inhalation of ipratropium is primarily a local, site-specific effect, not a systemic one. Much of an inhaled dose is swallowed as shown by fecal excretion studies. Following nebulization of a 1-mg dose to healthy volunteers, a mean of 4% of the dose was excreted unchanged in the urine.

Ipratropium bromide is minimally (0% to 9% in vitro) bound to plasma albumin and alpha 1acid glycoproteins. It is partially metabolized to inactive ester hydrolysis products. Following intravenous administration, approximately one-half is excreted unchanged in the urine. The half-life of elimination is about 1.6 hours after intravenous administration. Ipratropium bromide that reaches the systemic circulation is reportedly removed by the kidneys rapidly at a rate that exceeds the glomerular filtration rate. Autoradiographic studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier.

A pharmacokinetic study with 29 chronic obstructive pulmonary disease (COPD) patients (48–79 years of age) demonstrated that mean peak plasma ipratropium concentrations of 59±20 pg/ml were obtained following a single administration of 4 inhalations of ipratropium bromide HFA Inhaler (84 mcg). Plasma ipratropium concentrations rapidly declined to 24±15 pg/ml by 6 hours. When these patients were administered 4 inhalations q.i.d. (16 inhalations/day = 336 mcg) for 1 week, the mean peak plasma ipratropium concentration increased to 82±39 pg/ml with a trough (6 hours) concentration of 28±12 pg/ml at steady state. 

Special Populations

Geriatric Patients

In the pharmacokinetic study with 29 COPD patients, a subset of 14 patients was >65 years of age. Mean peak plasma ipratropium concentrations of 56±24 pg/ml were obtained following a single administration of 4 inhalations (21 mcg/puff) of ipratropium bromide HFA Inhaler (84 mcg). When these 14 patients were administered 4 inhalations q.i.d. (16 inhalations/day) for 1 week, the mean peak plasma ipratropium concentration only increased to 84±50 pg/ml, indicating that the pharmacokinetic behavior of ipratropium bromide in the geriatric population is consistent with younger patients.

Indications

DUOLIN Inhaler is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children (4 years of age and older) with reversible obstructive airway diseases like asthma and COPD, including chronic bronchitis and emphysema.

Dosage and Administration

The dosage of DUOLIN Inhaler is 2 inhalations, four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. It is recommended to “test-spray” three times before using for the first time and in cases where the aerosol has not been used for more than 24 hours. Avoid spraying into eyes.

DUOLIN Inhaler may be used with a Zerostat VT Spacer device in patients who find it difficult to synchronize aerosol actuation with inspiration of breath.

Contraindications

DUOLIN Inhaler is contraindicated in patients with a history of hypersensitivity to any of its components. Ipratropium bromide is contraindicated in patients who are hypersensitive to atropine or its derivatives.

DUOLIN Inhaler is contraindicated in patients with a history of hypersensitivity to soya lecithin or related food products such as soybean and peanut.

Warnings and Precautions

Levosalbutamol

Paradoxical Bronchospasm

Like other inhaled beta-adrenergic agonists, levosalbutamol can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, DUOLIN Inhaler should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister.

Deterioration of Asthma

Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of levosalbutamol than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and treatment regimen, with special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids. 

Use of Anti-Inflammatory Agents

The use of a beta-adrenergic agonist alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-­inflammatory agents, e.g., corticosteroids, to the therapeutic regimen. 

Cardiovascular Effects

Levosalbutamol contained in DUOLIN Inhaler, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of levosalbutamol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T-wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, levosalbutamol like all sympathomimetic amines should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Do Not Exceed Recommended Dose

Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected. 

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions may occur after administration of ipratropium bromide or racemic salbutamol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

If such a reaction occurs, DUOLIN Inhaler must be stopped at once and alternative treatment should be considered. The potential for hypersensitivity must be considered in the clinical evaluation of patients who experience immediate hypersensitivity reactions while receiving levosalbutamol.

Co-existing Conditions

Levosalbutamol, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmias; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressures have been seen in individual patients and could be expected to occur in some patients after the use of any beta-adrenergic bronchodilator.

Large doses of intravenous racemic salbutamol have been reported to aggravate pre-existing diabetes mellitus and ketoacidosis. As with other beta-adrenergic agonist medications, levosalbutamol may produce significant hypokalemia in some patients, possibly through intracellular shunting which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation. 

Ipratropium Bromide

Ipratropium bromide is a bronchodilator for the maintenance treatment of bronchospasm associated with COPD and is not indicated for the initial treatment of acute episodes of bronchospasm, where rescue therapy is required for rapid response.

Inhaled medicines, including ipratropium bromide may cause paradoxical bronchospasm. If this occurs, treatment with ipratropium bromide should be stopped and other treatments considered. 

Excessive Use and Use with other Muscarinic Antagonists

Ipratropium bromide should not be used more frequently or at higher doses than recommended (maximum recommended daily dose is 12 actuations = 240 mcg; minimum dosing interval is 4 hours).

Ipratropium bromide should not be administered concomitantly with other medications that contain a short- or long-acting muscarinic antagonist (e.g. tiotropium, glycopyrronium, aclidinium, umeclidinium).

Worsening of Narrow-Angle Glaucoma

Ipratropium bromide should be used with caution in patients with narrow-angle glaucoma.

Care should be taken to avoid spraying the mist into the eyes. Since the pressurized inhalation solution is applied via mouth piece and manually controlled, the risk for the mist entering the eyes is limited. There have been isolated cases of ocular complications (i.e., mydriasis, increased intraocular pressure, narrow angle closure glaucoma, eye pain) when aerosolised ipratropium bromide either alone or in combination with an adrenergic beta₂-agonist solution has come in contact with the eyes. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop. Miotic drops alone are not considered to be effective treatment.

Worsening of Urinary Retention

Ipratropium bromide should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Information for Patients

Patients should be cautioned to avoid spraying the aerosol into their eyes and be advised that this may result in precipitation or worsening of narrow-angle glaucoma, mydriasis, increased intraocular pressure, acute eye pain or discomfort, temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion. Patients should also be advised that should any combination of these symptoms develop, they should consult their physician immediately.

The action of DUOLIN Inhaler should last 4 to 5 hours or longer. DUOLIN Inhaler should not be used more frequently than recommended. Do not increase the dose or frequency of DUOLIN Inhaler without consulting your physician. If you find that treatment with DUOLIN Inhaler becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, medical attention should be sought immediately. While you are taking DUOLIN Inhaler, other inhaled drugs should be taken only as directed by your physician. If you are pregnant or nursing, contact your physician about use DUOLIN Inhaler. Appropriate use of DUOLIN Inhaler includes an understanding of the way it should be administered (see Patient’s Instructions for Use).

Since dizziness, accommodation disorder, mydriasis, and blurred vision may occur with use of DUOLIN Inhaler, patients should be cautioned about engaging in activities requiring balance and visual acuity such as driving a car or operating appliances or machinery.

Drug Interactions

Levosalbutamol Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should be used with caution with levosalbutamol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Beta-Blockers

Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-adrenergic agonists, such as levosalbutamol, but also may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution.

Diuretics

The ECG changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop and thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the co-administration of beta-agonists with non– potassium-sparing diuretics. Consider monitoring potassium levels.  

Monoamine Oxidase Inhibitors (MAO) or Tricyclic Antidepressants 

Levosalbutamol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of levosalbutamol on the cardiovascular system may be potentiated.  Consider alternative therapy in patients taking MAO or tricyclic inhibitors.

Ipratropium Bromide

Ipratropium bromide has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, that may be used in the treatment of COPD. With the exception of salbutamol, there are no formal studies fully evaluating the interaction effects of ipratropium bromide 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 long-acting muscarinic antagonist (e.g. tiotropium, glycopyrronium, aclidinium, umeclidinium).

Pregnancy 

Pregnancy Category C

There are no adequate and well-controlled studies of levosalbutamol and ipratropium combination inhaler in pregnant women. Because animal reproduction studies are not always predictive of human response, DUOLIN Inhaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

Because of the potential for beta-agonist interference with uterine contractility, use of DUOLIN Inhaler for the treatment of COPD during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Lactation

Levosalbutamol

Plasma concentrations of levosalbutamol after inhalation of therapeutic doses are very low in humans. It is not known whether levosalbutamol and ipratropium bromide are excreted in human milk.

Because of the potential for tumorigenicity shown for racemic salbutamol in animal studies, decision should be made whether to discontinue nursing or to discontinue levosalbutamol, taking into account the importance of the drug to the mother.

Ipratropium Bromide

No specific studies have been conducted on the excretion of ipratropium bromide in breast milk. It is considered unlikely that ipratropium bromide would reach the infant to an important extent, especially when administered by inhalation. However, caution should be exercised when ipratropium bromide is administered to nursing mothers. The benefits of ipratropium bromide use during lactation should therefore be weighed against possible effects on the infant.

Pediatric Use

Levosalbutamol

The safety and efficacy of levosalbutamol has been established in pediatric patients, 4 years of age and older. Use of levosalbutamol in children is supported by evidence from adequate and well-controlled studies of levosalbutamol in adults, considering that the pathophysiology, systemic exposure of the drug, and clinical profile in pediatric and adult patients are substantially similar.

Ipratropium Bromide

The efficacy and safety in children and adolescents under 18 years has not been established. Ipratropium bromide is not indicated for pediatric patients.  Safety and effectiveness of DUOLIN Inhaler in pediatric patients below the age of 4 years have not been established.

Geriatric Use

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Levosalbutamol is known to be substantially excreted by the kidneys; hence, the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Undesirable Effects

Levosalbutamol

Use of levosalbutamol may be associated with the following:

• Paradoxical bronchospasm
• Cardiovascular effects
• Immediate hypersensitivity reactions
• Hypokalemia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rate observed in the clinical trials of a drug cannot be directly compared with the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults and Adolescents 12 years of Age and Older

Adverse reaction information concerning levosalbutamol in adults and adolescents is derived from two-8 week, multicenter, randomized, double-blind, active – and placebo-controlled trials in 748 adult and adolescent patients with asthma that compared levosalbutamol inhaler and placebo inhaler. Table 1 lists the incidence of all adverse reactions (whether considered by the investigator to be related or unrelated to the drug) from these trials that occurred at a rate of 2% or greater in the group treated with levosalbutamol and more frequently than in the placebo inhaler group.

* This table includes all adverse reactions (whether considered by the investigator to be related or unrelated to drug) from the trial that occurred at a rate of 2% or greater in the group treated with levosalbutamol and more frequently in the placebo inhaler group.

Adverse reactions reported by less than 2% and at least or more of the adolescent and adult patients receiving levosalbutamol and by a greater proportion than receiving  placebo inhaler include cyst, flu syndrome, viral infection, constipation, gastroenteritis, myalgia, hypertension, epistaxis, lung disorder, acne, herpes simplex, conjunctivitis, ear pain, dysmenorrhea, hematuria, and vaginal moniliasis. There were no significant laboratory abnormalities observed in these studies. 

Adverse reaction of levosalbutamol in pediatric patients is derived from a 4-week, randomized, double-blind trial of levosalbutamol and placebo inhaler in 150 children aged 4 to 11 years with asthma. Table 2 lists the adverse reactions reported for levosalbutamol in children at a rate of 2% or greater and more frequently than for placebo.

* This table includes all adverse reactions (whether considered by the investigator to be related or unrelated to drug) from the trial that occurred at a rate of 2% or greater in the group treated with levosalbutamol and more frequently in the placebo inhaler group.

The incidence of beta-adrenergic adverse reactions (e.g., tremor, nervousness) was low and comparable across all treatment groups, including placebo. 

Postmarketing Experience

In addition to the adverse events reported in clinical trials, the following adverse events have been observed in post approval use of levosalbutamol. These events have been chosen for inclusion due to their seriousness, their frequency of reporting, or their likely beta-mediated mechanism: angioedema, anaphylaxis, arrhythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles), asthma, chest pain, cough increased, dysphonia, dyspnea, gastroesophageal reflux disease (GERD), metabolic acidosis, nausea, nervousness, rash, tachycardia, tremor, and urticaria.

In addition, levosalbutamol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, headache, and drying or irritation of the oropharynx.

Ipratropium Bromide

Adverse reactions to ipratropium bromide are similar in nature to reactions to other anticholinergic bronchodilators and may include cardiovascular effects (atrial arrhythmias and tachycardia), ocular disorders (e.g. blurred vision), dysuria, urinary retention, gastrointestinal disorders (e.g., constipation and dry mouth), paradoxical bronchospasm, cough and immediate hypersensitivity reactions, including anaphylaxis.

The commonly observed side effects for the patients who have been treated with ipratropium include:

General disorders: Headache, pain, influenza-like symptoms, back pain, chest pain and fatigue

Nervous system disorders: Dizziness

Gastro-intestinal disorders: Dryness of mouth, nausea, diarrhea; abdominal pain, vomiting, constipation

Respiratory disorder: Rhinitis, bronchitis, dyspnea, coughing, chronic obstructive airway disease, upper respiratory tract infection, pharyngitis, asthma, sinusitis

Special senses –other disorders: Taste perversion

Urinary system disorders: Urinary tract infections.

Vision disorders: Conjunctivitis

The uncommon undesirable effects included

Nervous system disorders: Dysphonia

Gastro-intestinal disorders: Constipation, dyspepsia

Musculoskeletal disorders: Myalgia

The most frequent adverse events reported in clinical trials were headache, throat irritation, cough, dry mouth, gastrointestinal motility disorders (constipation, diarrhea, vomiting), dizziness and nausea.

As with other inhaled therapy including bronchodilators, cough, local irritation, paradoxical bronchospasm and in very rare instances, exacerbation of symptoms have been observed.

Postmarketing Reports

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: blurred vision, glaucoma, increased intra-ocular pressure, eye pain, mydriasis, halo vision, conjunctival hyperemia, corneal edema, accommodation disorder

Cardiac disorders: palpitation, supraventricular tachycardia, atrial fibrillation, increased heart rate.

Respiratory, thoracic and mediastinal disorders: Pharyngeal edema, dry throat, bronchospasm, paradoxical bronchospasm, laryngospasm, throat irritation, cough

Gastrointestinal disorders: Nausea, gastrointestinal motility disorder, diarrhea, constipation, vomiting, stomatitis, edema mouth

Skin and subcutaneous disorders: skin rash, pruritus, angioedema, urticaria

Renal disorders: Urinary retention

Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

If you experience 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 program of India by calling on 18002677779 (Cipla Number) or you can report to PvPI on 1800 180 3024. By reporting side-effects, you can help provide more information on the safety of this product.

Overdosage

Levosalbutamol

The expected symptoms with overdosage are those of excessive beta-adrenergic receptor stimulation and/or occurrence or exaggeration of any of the symptoms listed under adverse reactions, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and, even, death may be associated with the abuse of levosalbutamol.

Treatment consists of discontinuation of levosalbutamol together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial in treating overdosage of levosalbutamol.