Instructions for Ascoril tablets No. 50
Composition
active ingredients: 1 tablet contains salbutamol sulfate equivalent to salbutamol 2 mg, bromhexine hydrochloride 8 mg, guaifenesin 100 mg;
excipients: calcium hydrogen phosphate, corn starch, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), talc, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white, round, flat tablets with beveled edges, with a break line on one side.
Pharmacotherapeutic group
Combined remedies used for coughs and colds. Expectorants. Combinations.
ATX code R05C A10.
Pharmacological properties
Pharmacodynamics
Salbutamol is a direct sympathomimetic, a selective agonist of β2-adrenergic receptors. The main action of β-adrenergic agonists is the ability to stimulate adenylate cyclase, an enzyme that catalyzes the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). An increase in the amount of cAMP causes relaxation of bronchial smooth muscle and inhibits the release of mediators of immediate hypersensitivity from cells, especially mast cells. Salbutamol relaxes the smooth muscles of the bronchi, uterus, vascular bed of skeletal muscles. Salbutamol has a stronger and longer effect on β2-adrenergic receptors than isoproterenol. Salbutamol can also improve the mechanisms of mucociliary transport.
Bromhexine has an expectorant and mucolytic effect. Bromhexine is a derivative of benzylamine and vasicin. It increases the volume of sputum, reduces its viscosity and promotes its evacuation from the bronchi; stimulates the hydrolytic depolymerization of mucoprotein fibers and stimulates the activity of the ciliated epithelium. It is known that bromhexine causes the release of lysosomal enzymes by the bronchial glands.
Other pharmacological effects of bromhexine are also known: increased secretion of exocrine glands (e.g., lacrimation) and increased production of pulmonary surfactant. Simultaneous use of bromhexine with oxytetracycline, erythromycin, ampicillin, amoxicillin leads to an increase in their concentration in sputum.
It is believed that the increase in exocrine gland secretion during the use of bromhexine may be contributed by the metabolite of bromhexine, ambroxol (NA-872).
Guaifenesin. The action of guaifenesin is to stimulate receptors in the gastric mucosa and reflexively stimulate the secretion of the glands of the respiratory tract. As a result, the volume increases and the viscosity of bronchial secretion decreases.
Pharmacokinetics
Salbutamol.
Salbutamol is well absorbed from the digestive tract, its bioavailability is from 50% to 85%. After oral administration, the maximum concentration (Cmax) in the blood plasma occurs after 1–4 hours (Tmax). Food does not affect the bioavailability of salbutamol. It binds to proteins in an amount of 10%. The volume of distribution (Vd) is 156 ± 38 l. Salbutamol is metabolized in the liver to an inactive sulfate conjugate. Salbutamol is excreted mainly by the kidneys. From 64% to 98% is excreted in the urine and 1.2–7% in the feces. The half-life of salbutamol is 3–6.5 hours.
Bromhexine.
Bromhexine is well absorbed from the digestive tract. The maximum concentration of bromhexine in the blood serum occurs approximately 1 hour after taking the drug. It is metabolized in the liver to the active metabolite - ambroxol. Bromhexine is excreted mainly in the urine in the form of metabolites, only a small part of it is excreted unchanged. The half-life of bromhexine is 6.5 hours.
Guaifenesin.
Guaifenesin is well absorbed from the gastrointestinal tract. 60% of guaifenesin is hydrolyzed in the blood within 7 hours to form b(2-methoxyphenoxy)-lactic acid. Guaifenesin is excreted in the urine as metabolites. The half-life of guaifenesin is 1 hour.
Indication
Symptomatic treatment of productive cough in various respiratory diseases accompanied by bronchospasm.
Contraindication
Hypersensitivity to salbutamol, other sympathomimetics, bromhexine, guaifenesin or any of the other components of the drug. Coronary insufficiency, arrhythmia, other severe cardiovascular diseases, hyperthyroidism, severe liver dysfunction, gastric and duodenal ulcers or a history of peptic ulcer disease. Porphyria.
Interaction with other medicinal products and other types of interactions
The simultaneous use of salbutamol and other oral sympathomimetics is not recommended, as such a combination may lead to cardiovascular disorders.
In healthy volunteers who took digoxin for 10 days, an increase in its concentration from 16% to 22% in the blood serum was observed after a single administration of salbutamol.
The clinical significance of these observations in patients with obstructive airways disease receiving salbutamol and digoxin for long periods of time is not yet fully understood. However, it is advisable to monitor serum digoxin levels in patients receiving digoxin and salbutamol concomitantly.
Hypokalemia, which develops as a result of the use of drugs containing salbutamol, may increase with the simultaneous use of diuretics. As a result, the risk of developing arrhythmias increases when using cardiac glycosides against the background of such treatment.
The effects of salbutamol may be reduced by the concomitant use of β-blockers, especially non-selective ones (such as propranolol), and may also be enhanced by the concomitant use of xanthines (such as theophylline).
β-blockers can not only block the bronchodilator effect of β-agonists, but also cause bronchospasm in patients with bronchial asthma. Therefore, the use of β-blockers is contraindicated in patients with asthma.
However, in certain circumstances, such as prophylaxis after myocardial infarction, β-blockers may be considered for patients with asthma. In such cases, they should be used with caution.
β-agonists may potentiate ECG changes and/or hypokalemia caused by potassium-sparing diuretics (such as loop and thiazide diuretics).
Although the clinical significance of these effects is unknown, caution is recommended when β-agonists are used concomitantly with potassium-sparing diuretics.
Salbutamol should not be used simultaneously with inhalation anesthetics, adrenaline, tricyclic antidepressants and corticosteroids.
Bromhexine should not be administered simultaneously with drugs containing codeine. With simultaneous use of bromhexine and drugs that irritate the digestive tract (for example, nonsteroidal anti-inflammatory drugs), mutual enhancement of the irritating effect on the gastric mucosa is possible. Simultaneous administration with antibiotics (amoxicillin, erythromycin, cefuroxime, doxycycline), sulfonamide drugs contributes to an increase in their concentration in the bronchial secretion. When taken simultaneously with drugs that suppress the cough center, difficulty in the discharge of thinned sputum (accumulation of bronchial secretion in the respiratory tract) is possible. Simultaneous administration with bronchodilators is possible. Bromhexine is not compatible with alkaline solutions.
Guaifenesin enhances the effects of central nervous system depressants and ethanol. It may also cause false-positive results in diagnostic tests for 5-hydroxyindoleacetic acid and vanillylmandelic acid in urine.
Guaifenesin enhances the effects of sedatives and muscle relaxants.
Application features
Salbutamol, like other β-adrenergic stimulators, should be prescribed with caution to patients with seizure disorders, diabetes mellitus, and cardiovascular disorders (arterial hypertension).
Salbutamol may affect the cardiovascular system, which is manifested by an acceleration of the pulse rate, an increase in blood pressure, changes in the ECG, such as: flattening of the T wave, prolongation of the QT interval, depression of the ST segment. Therefore, salbutamol should be used with caution in patients with diseases of the cardiovascular system, especially in arterial hypertension.
As with any other β-adrenergic agonist, clinically significant changes in systolic and diastolic blood pressure may occur in some patients.
Sudden and progressive worsening of asthma is a life-threatening condition requiring the use of corticosteroids or an increase in their dose. The need to increase the dose of salbutamol indicates worsening asthma control and requires a review of therapy, if necessary - the appointment of corticosteroids.
Salbutamol may cause paradoxical bronchospasm with sudden worsening of dyspnea, which may be life-threatening. In this case, the drug should be discontinued immediately and a doctor should be consulted.
Isolated cases of myocardial ischemia have been reported in association with the use of salbutamol. Patients with cardiac disease (e.g. coronary artery disease) treated with salbutamol should seek medical attention if they experience chest pain or other symptoms suggestive of worsening cardiac disease. Attention should be paid to assessing symptoms such as shortness of breath and chest pain, which may be due to both cardiac and respiratory disease.
As with other β-adrenergic agonists, salbutamol may cause reversible metabolic changes, such as an increase in blood sugar levels. As a result, there have been isolated reports of ketoacidosis in diabetic patients. Concomitant use of corticosteroids may exacerbate this condition. Blood glucose levels should be monitored before and during treatment in such patients.
Guaifenesin should be used with caution in the treatment of cough with excessive sputum production, persistent or chronic cough resulting from smoking, asthma, chronic bronchitis, emphysema.
Bromhexine is not used in patients with gastric or duodenal ulcers or a history of peptic ulcer disease, as bromhexine may affect the mucous membrane of the gastrointestinal tract. If there is a history of gastric bleeding, the drug should be used under the supervision of a physician. When treating with the drug, it is necessary to drink a sufficient amount of fluid, which increases the expectorant effect of bromhexine.
Very rarely, severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and acute generalized exanthematous pustulosis have occurred with the use of bromhexine. If changes appear on the skin and mucous membranes, you should immediately consult a doctor and stop using the drug.
In case of impaired bronchial motility, accompanied by the formation of a large amount of bronchial secretion (malignant cilia syndrome), the drug should be used with extreme caution due to possible stagnation of secretions.
The drug should be used with caution in patients with glaucoma.
In case of impaired renal function (including severe renal failure) or liver disease (with moderate and mild hepatic failure), it should be used with extreme caution (reducing the dose or increasing the time interval between applications).
Periodic monitoring of liver function is recommended, especially with prolonged use.
Do not administer the drug before anesthesia.
The drug should not be used in patients with hypertrophic cardiomyopathy.
Methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216), which are part of the medicinal product, may cause allergic reactions (possibly delayed).
Ability to influence reaction speed when driving vehicles or other mechanisms
You should refrain from driving or operating other machinery during treatment with the drug.
Use during pregnancy or breastfeeding
Do not apply.
Method of administration and doses
Adults and children over 12 years of age should take 1 tablet orally 3 times a day.
Children aged 6 to 12 years: ½ – 1 tablet 3 times a day.
The duration of treatment is determined individually.
Children
Do not prescribe the medicine to children under 6 years of age.
Overdose
Symptoms: agitation, confusion, respiratory depression, rapid breathing, impaired consciousness, ataxia, diplopia, mild metabolic acidosis, arrhythmias, chest pain, hypotension up to shock, palpitations, tachycardia and severe tremor, especially in the hands. Gastrointestinal complaints, including nausea and vomiting, convulsions, extrasystole, drowsiness, headache, hypokalemia, abdominal pain, exacerbation of gastric ulcer.
The most common signs and symptoms of salbutamol overdose are transient changes pharmacologically induced by β-agonists, such as tachycardia, tremor, hyperactivity and metabolic disturbances, including hypokalemia (see sections 4.4 and 4.8).
Hypokalemia may occur as a result of salbutamol overdose, therefore serum potassium levels should be monitored. Lactic acidosis has been reported with high therapeutic doses or overdose of short-acting β2-agonists, therefore serum lactate levels should be monitored and metabolic acidosis should be monitored accordingly, especially in the case of persistent or increasing tachypnea despite improvement in bronchospasm symptoms such as wheezing.
A mild to moderate overdose of guaifenesin may cause dizziness, gastrointestinal upset, nausea, vomiting, or decreased muscle tone. Very high doses of guaifenesin may cause symptoms such as agitation, confusion, and respiratory depression. There have been rare reports of bladder or kidney stones in patients who have taken large amounts of guaifenesin over a long period of time.
Treatment: Symptomatic therapy, electrocardiographic monitoring is indicated to monitor cardiac function.
Adverse reactions
On the part of the immune system: hypersensitivity reactions, including rash, itching, anaphylactic reactions, including drug hypersensitivity syndrome with eosinophilia and systemic symptoms, anaphylactic shock, angioedema, urticaria, oropharyngeal edema, facial edema; in isolated cases - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), acute generalized exanthematous pustulosis.
On the part of the digestive tract: dyspeptic phenomena, nausea, vomiting, diarrhea, abdominal pain, exacerbation of gastric ulcer/intestinal ulcer, gastralgia, unpleasant taste in the mouth.
Nervous system: tremor, myalgia, headache, hyperactivity, dysgeusia, dizziness, anxiety, insomnia, oropharyngeal paresthesia.
Cardiovascular system: tachycardia; peripheral vasodilation; cardiac arrhythmias, including ventricular fibrillation, supraventricular tachycardia and extrasystole; hypotension or hypertension; palpitations; myocardial ischemia; collapse.
From the respiratory system: respiratory disorders, increased cough.
Salbutamol may cause paradoxical bronchospasm, which is a life-threatening condition. If this occurs, the drug should be discontinued immediately and alternative treatment should be instituted.
Metabolism and metabolism: hypokalemia. Potentially, the use of b2-agonists can cause severe hypokalemia, increased serum lactate content/lactic acidosis.
Others: myospasm, muscle cramps, feeling of pressure in the muscles, hyperthermia, chills, mydriasis, bladder atony, increased sweating, hyperglycemia, thrombocytopenia.
Some patients may develop a transient increase in blood aminotransferase levels caused by bromhexine.
Expiration date
2 years.
Storage conditions
Store in a dry place, protected from light, at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 5 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Glenmark Pharmaceuticals Ltd.
Location of the manufacturer and its business address
Precinct No. E-37/39, M.I.D.C., Satpur, Nasik – 422 007, India.
