(Fixed dose combination of Salbutamol Sulphate, Bromhexine hydrochloride, Guaifenesin and Menthol)
For the use only of a Registered Medical Practitioner or Hospital or a Laboratory.
(Fixed dose combination of Salbutamol Sulphate, Bromhexlne hydrochloride, Guaifenesin and Menthol)
Each 10mI contains:
Salbutamol Sulphate BP equivalent to Salbutamol 2mg
Bromhexine Hydrochloride BP 4mg
Guaifenesin USP 100mg
Menthol BP 1mg
Flavoured Syrup base q.s.
Colour: Sunset Yellow FCF
ASCOREX EXPECTORANT contains Salbutamol Sulphate, a selective beta-2 agonist Bromhexine hydrochloride, an expectorant/mucolytic agent; Guaifenesin, an expectorant and Menthol, a soothing agent.
1. Salbutamol Sulphate is a selective beta-2 agonist with bronchodilator property. Chemically it is 2-(hydroxymethyl) 4-[1-hydroxy- 2-(tert-butylamino) ethyl] phenol with a molecular formula of C13H21NO3 and Molecular weight of 239.311.
2. Bromhexine hydrochloride is a mucolytic agent. The drug is a benzylamine derivative and also a derivative of vasicine and adhatodic acid, alkaloids obtained from the plant Adhatoda vasica. Its chemical formula is C14H20Br2N2 and the Molecular weight is 376.13.
3. Guaifenesin is an expectorant that was first approved by the FDA In 1952. Chemically it is 3-(2-methoxyphenoxy) propane-1, 2-diol with a chemical formula of C10H14O4 and Molecular weight of 198.216 g/mol.
4. Menthol is a demulcent/soothing agent with a chemical name of p-Menthan-3-ol; 2-lsopropyl-5 methylcyclohexanol and a molecular formula of C10H20O. It has a molecular weight of 156.3.
Salbutamol is a direct-acting sympathomimetic agent which demonstrates relatively selective action on beta-2 adrenoceptors. The prime action of beta-adrenergic drugs is to stimulate adenyl cylase, the enzyme which catalyzes the formation of cyclic-3, 5-adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Salbutamol relaxes the smooth muscle of the bronchi (causing bronchodilation or widening of the airway), uterus, and skeletal muscle vascular bed. Salbutamol is more potent and longer acting beta-2 adrenoceptor agonist as compared to lsoproterenol. Salbutamol may also reduce chemical mediator release from pulmonary mast cells and improve mucociliary transport mechanisms.
Bromhexine is an expectorant/mucolytic agent. Following oral administration, bromhexine has increased sputum volume and reduced the viscosity of bronchial secretions in chronic bronchitis patients. The drug has been reported to induce hydrolytic depolymerization of mucoprotein fibers and stimulate activity of the ciliated epithelium. An increase in lysosomal activity facilitated by bromhexine has been postulated. Improvements in pulmonary function in bronchitis patients appear secondary to easier expectoration.
Other pharmacological effects of bromhexine have been reported, including enhancement of secretion from exocrine glands (e.g., tear production) and an increase in pulmonary surfactant production. An effect of bromhexine on increasing sputum concentrations of various antibiotics (e.g., oxytetracycilne, erythromycin, ampicillin, amoxicillin) has also been reported. It has been suggested that metabolite of bromhexine, ambroxol (NA-872), may contribute to enhanced secretion from exocrine glands during Bromhexine administration.
Guaifenesin is an expectorant which is thought to act by irritating the gastric mucosa and subsequently stimulating respiratory tract secretions. This increase in fluid increases the volume and decreases the viscosity of bronchial secretions. It was first approved by the Food and Drug Administration (FDA) in 1952.
Menthol is chiefly used to relieve symptoms of bronchitis, sinusitis, and similar conditions. Menthol exerts soothing and counter-irritant effects on upper respiratory mucosa. It has been suggested that the apparent benefits of menthol in nasal congestion may be due to an effect on calcium channels of sensory nerves.
Salbutamol is well absorbed from the gastrointestinal tract with bioavailability of approximately 50% to 85%. Peak plasma concentrations (Cmax) occur 1 to 4 hours (Tmax) after oral administration of salbutamol. Food does not affect the bioavailability of salbutamol. Plasma protein binding for salbutamol is 10% and volume of distribution (Vd) is 156+/-38 liters. Salbutamol is metabolised in the liver to form active metabolite, 4-O-Sulphate ester. Excretion of salbutamol is primarily renal. Approximately 64% to 98% of the dose is recovered in the urine and 1.2% to 7% eliminated in feces. The elimination half-life of salbutamol is 3 to 6.5 hours.
Bromhexine is well absorbed from the gastrointestinal tract. Peak serum concentrations of bromhexine occur approximately 1 hour following oral administration. Bromhexine is extensively metabolised in the liver to form active metabolite, ambroxol. Bromhexine is excreted primarily in the urine as metabolites. Only small amounts appear as unchanged drug. The elimination half-life of bromhexine is 6.5 hours.
Guaifenesin is well absorbed from the gastrointestinal tract. 60% of guaifenesin is hydrolyzed in blood within 7 hours with the formation of Beta-2-methoxyphenoxy-Iactlc acid. Excessive use of guaifenesin may result in urolithiasis; the resultant stones contain the metabolite of guaifenesin, beta-2- methoxyphenoxy-lactic acid. Guaifenesin is excreted in the urine in the form of metabolites. The plasma half-life of guaifenesin is 1 hour.
After absorption, menthol is excreted in the urine and bile as a glucuronide.
INDICATIONS AND USAGE
ASCOREX EXPECTORANT is indicated for the symptomatic relief in the treatment of productive cough associated with bronchospasm in various respiratory disorders like Pneumonia, COPD, Bronchial asthma, emphysema, acute and chronic bronchitis, etc.
DOSAGE AND ADMINISTRATION
• Adults and Children over 12 years: 10 mL (2 teaspoons) three times a day.
• Children from 6 to 12 years: 5 mL (1 teaspoon) three times a day.
• Children from 2 to 5 years: 2.5 mL(1/2 teaspoon) three times a day.
• Not recommended in children below 2 years.
USE IN SPECIAL POPULATIONS
Animal reproduction studies have not been conducted with ASCOREX EXPECTORANT. It is also not known whether ASCOREX EXPECTORANT can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ASCOREX EXPECTORANT should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus.
ASCOREX EXPECTORANT is not recommended in lactating mothers.
ASCOREX EXPECTORANT is not recommended in children less than 2 years of age.
Known or suspected hypersensitivity to any of the ingredients.
WARNINGS AND PRECAUTIONS
• Salbutamol, as with all sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes meliltus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen and could be expected to occur in some patients after use of any beta-adrenergic bronchodilator.
• Salbutamol, like all other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, and/or symptoms. 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. Therefore, salbutamol should be used with caution in patIents with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
• Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of salbutamol than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti inflammatory treatment; e.g., Corticosteroids.
• Salbutamol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, salbutamol should be discontinued immediately and alternative therapy instituted.
• Immediate hypersensitivity reactions may occur after administration of salbutamol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. Rarely, erythema multiforme and Stevens Johnson syndrome have been associated with the administration of oral salbutamol in children.
• Precaution should be taken while using Guaifenesin in treatment of cough accompanied by too much mucus or persistent or chronic cough such as that which occurs with smoking, asthma, chronic bronchitis, or emphysema.
• Bromhexine should be used cautiously in patients with gastric or duodenal ulcer.
ASCOREX EXPECTORANT is generally well tolerated and adverse events are generally mild and transient. The adverse events reported with the individual ingredients are as mentioned below:
The adverse reactions to salbutamol are similar in nature to reactions to other sympathomimetic agents. The reactions are generally transient in nature. The most frequent adverse reactions to salbutamol are nervousness, tremor, headache, tachycardia, and palpitations. Less frequent adverse reactions are muscle cramps, insomnia, nausea, weakness, dizziness, drowsiness, flushing, restlessness, irritability, chest discomfort, and difficulty in micturition. Rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema have been reported after the use of salbutamol. In addition, salbutamol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vomiting, vertigo, central nervous system stimulation, unusual taste, and drying or irritation of the oropharynx.
Adverse effects of bromhexine include gastrointestinal symptoms (nausea, epigastric pain, vomiting), headache, dizziness, and skin rash; elevations in liver function tests have been reported in a few patients.
Adverse effects are primarily minor gastrointestinal complaints. Urolithiasis has been associated with excessive use of guaifenesin.
Ingestion of menthol is reported to cause severe abdominal pain, nausea, vomiting, vertigo, ataxia, drowsiness, and coma.
Diuretics: The ECG changes and/or hypokalemia that may result from the administration of non potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists.
Beta Blockers: Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as salbutamol, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta blockers.
Monoamine Oxidase Inhibitors: Hypertensive crises and other adverse effects occur frequently with the concurrent use of indirect-acting sympathomimetics. Direct-acting beta adrenergic agonist drugs should theoretically not interact with monoamine oxidase (MAO) inhibitors. However, two case reports have described adverse effects, including tachycardia and hypomania, attributed to such an interaction.
Digoxin: Decreases of 16% to 22% in serum digoxin levels were seen after single-dose administration of salbutamol to healthy volunteers who had been receiving digoxin for 10 days.
The concomitant use of salbutamol and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Animal or human studies of ASCOREX EXPECTORANT have not been performed to assess the carcinogenic and mutagenic potential, or the effect on fertility.
No overdosage has been reported with ASCOREX EXPECTORANT. Literature mentions reports of overdosage with salbutamol generally describing the features that may be expected such as tachycardia, CNS stimulation, tremor, hypokalaemia, and hyperglycaemia. Symptomatic treatment of the adverse effects has proved successful.
The plasma-potassium concentration and pulse rate have been found to correlate with the plasma concentration of salbutamol. Gastrointestinal discomfort, nausea, and vomiting have occasionally been reported with Guaifenesin, particularly in very large doses. Urinary calculi (Urolithiasis) have been reported in patients consuming large quantities of over-the-counter preparations containing guaifenesin.
Store below 25°C. Protect from light.
Keep all Medicines out of reach of children.
Bottle of 100 ml.
NAFDAC Reg. No. A4-0918
GLENMARK PHARMACEUTICALS LTD.
PLOT NO. E-37, 39, D-ROAD,
M.I.D.C. INDUSTRIAL AREA,
SATPUR, NASIK -422 007, INDIA.