International non-proprietary name: Salbutamol sulfate + Bromhexine hydrochloride + Guaifenesin

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Composition

Active ingredients: 2.41 mg equivalent to 2 mg of salbutamol in 10 ml of solution

contains salbutamol sulfate, 4 mg bromhexine hydrochloride, 100 mg guaifenesin.

Excipients: menthol (perfume), propylene glycol, sorbitol solution, glycerol, sodium carmellose,

aspartame (sweetener), anhydrous citric acid, sodium benzoate, sodium citrate,

strawberry flavoring, purified water.

 

Description

It is a clear colorless solution.

 

Pharmacotherapeutic group

Combined expectorants (with the exception of the combination with antitussives).

ATC code:R05CA10.

 

pharmacological properties

Pharmacodynamics

Salbrofen syrup is a combined drug that has bronchodilator, mucolytic and expectorant effects due to the pharmacological properties of its components and is used in various diseases of the respiratory tract.

Salbutamol is a selective agonist of β2-adrenoreceptors. In therapeutic doses, it affects the β2-adrenoceptors of the bronchial muscle, and has an insignificant or no effect on the β1-adrenoreceptors of the myocardium. By reducing the tone of the bronchial muscle, it has a pronounced broncholytic effect, prevents or eliminates bronchospasm, and reduces resistance in the respiratory tract. Increases the vital capacity of the lungs. Increases mucociliary clearance (up to 36% in case of chronic bronchitis), stimulates mucus secretion, activates the function of the mobile epithelium.

When taken in therapeutic doses, it acts on β2-adrenoceptors of bronchial muscles, providing short-term (from 4 to 6 hours) bronchodilation during reversible bronchoobstruction. In recommended therapeutic doses, it does not have a negative effect on the cardiovascular system, does not increase arterial pressure. To a lesser extent, it has a positive chrono- and inotropic effect compared to drugs from this group. Dilates coronary arteries. It has a number of metabolic effects: it reduces the concentration of potassium in the blood serum, affects glycogenolysis and insulin secretion, has a hyperglycemic (especially in patients with bronchial asthma) and lipolytic effect, increases the risk of developing acidosis.

Bromhexine hydrochloride is a mucolytic (secretolytic), expectorant and weak antitussive agent. Mucolytic effect is associated with depolymerization of mucoprotein and mucopolysaccharide fibers and increase of serous component of bronchial secretion. During various diseases of the respiratory system, it reduces the thickness of sputum and increases mucociliary clearance. Stimulates production of endogenous surfactant (surfactant), which provides stability in alveolar cells during respiration.

Guaifenesin increases the secretory function of the bronchial glands. It has an expectorant effect by increasing the volume and reducing the viscosity of mucus in the trachea and bronchi. The increase in secretion occurs both through a direct effect on bronchial glands (stimulation of secretion from bronchial glands and removal of acid glycoproteins from acinar cells) and through a reflex pathway (irritation of afferent parasympathetic fibers of the gastric mucosa and inhibition of the respiratory center). Increasing the tone of the vagus nerve stimulates the secretion of bronchial secretion. By strengthening the activity of the mucous ciliated epithelium secreted by the bronchial glands, it leads to an increase in the effectiveness of the cough reflex and facilitates the evacuation of sputum from the respiratory tract. Guaifenesin maintains its expectorant effect for 24 hours. Guaifenesin also has an anxiolytic effect.

Menthol has a local numbing and calming effect, reduces the feeling of irritation in the mucous membrane of the throat, freshens the breath.

Pharmacokinetics

Salbutamol

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. After oral administration of salbutamol in a dose of 4 mg, the maximum plasma concentration is 5.1-11.7 μg/ml and reaches 2.5-3 hours. Bioabsorption is 50%. Its combination with plasma proteins is 10%. During the "first pass" through the liver, it is significantly metabolized with the formation of inactive 4'-О-sulfate (phenol sulfate) metabolite. It does not significantly penetrate the blood-brain barrier, but crosses the placental barrier. It is excreted from the body mainly by the kidneys unchanged or in the form of metabolites within 24 hours; 50% of the drug taken inside is excreted in 4 hours. A very small part of the dose is excreted in the feces. The elimination half-life (t½) is 5 hours.

Bromhexine hydrochloride

After ingestion, it is quickly and completely absorbed in the body. The maximum plasma concentration in blood serum is reached in 1 hour. During the "first pass" through the liver, it undergoes significant metabolism with the formation of the active N-demethylated metabolite ambroxol. It is highly bound to plasma proteins. It accumulates in the lung tissue in the highest concentrations. It passes through the hematoencephalic barrier and a small amount through the placental barrier. It is excreted from the body mainly in the form of metabolites (85-90%) with the kidneys, and a small part (4%) with feces. 70% of the ingested dose is excreted within 24 hours. The elimination half-life (t½) is approximately 12 hours.

Guaifenesin

It is quickly absorbed from the gastrointestinal tract (25-30 minutes after ingestion). It is metabolized by oxidation and demethylation in the liver. It is rapidly hydrolyzed (60% within 7 hours) and then excreted in the urine as its main metabolite beta-(2-methoxyphenoxy) lactic acid. t½ is 1 hour. Penetrates into tissues containing acidic mucopolysaccharides. It is excreted from the lungs (sputum) and kidneys in the form of both unchanged and inactive metabolites.

 

Instructions for use

Salbrofen syrup is indicated for the symptomatic treatment of cough in the following diseases accompanied by bronchospasm of the respiratory tract or difficult sputum removal:

- acute and chronic bronchitis, obstructive bronchitis, bronchial asthma, pneumonia, pulmonary emphysema and bronchospasm, thick sputum, as well as other bronchopulmonary diseases accompanied by sputum removal problems.

- complex therapy of acute respiratory diseases.

 

Contraindications

Hypersensitivity to bromhexine or any of the other components of the drug.

Peptic ulcer of the stomach and duodenum (period of exacerbation).

Heart rhythm disturbances (arrhythmia: paroxysmal tachycardia, ventricular extrasystole).

Patients with ischemic heart disease or risk factors for CVD.

Severe liver and kidney failure.

Decompensated diabetes.

The first trimester of pregnancy.

Lactation period.

Pheochromocytoma.

Hyperthyroidism.

 

Special instructions and precautions

It should not be taken without a doctor's advice in case of constant and chronic (for example, smoking, bronchial asthma, emphysema, chronic bronchitis), as well as cough accompanied by excessive sputum secretion.

The drug should be used very carefully in patients with severe diseases of the cardiovascular system (CVD, arrhythmia and heart failure).

Salbutamol can cause an increase in the level of glucose in the blood serum, so it is recommended to control the level of glucose in the blood initially in patients suffering from diabetes.

The drug can increase intraocular pressure, so it should be used with caution in patients suffering from glaucoma.

The drug stimulates the activity of the thyroid gland; should be used with caution in individuals with hyperthyroidism. Caution should be exercised in hypokalemia, as β2-agonists may decrease blood potassium levels.

It should be used with caution in patients with a history of seizures. Thus, the drug can cause central nervous system alertness.

No special studies have been conducted on the use of the drug in case of liver and kidney failure. It should be used with caution in patients with kidney, liver and peptic ulcer disease.

Guaifenesin may cause pink urine, but this is not clinically significant.

It is necessary to be careful when prescribing the drug in liver and kidney diseases, as well as during pregnancy and lactation.

 

Interaction with other drugs

Antitussives, such as codeine, which inhibit the removal of sputum, and drugs that reduce mucus production, such as atropine, may cause sputum to accumulate in the lungs. Therefore, Salbrofen syrup should not be used simultaneously with these drugs.

Bromhexine accelerates the absorption of antibacterial agents and improves their penetration into the respiratory tract.

Atropine and other anti-muscarinic drugs such as amantadine, tricyclic antidepressants, antihistamines, haloperidol, and procainamide (eg, ipratropium) may reduce ciliary motility and mucociliary clearance, causing mucus accumulation in the airways.

Use together with anticholinergic agents (including inhalation) can lead to an increase in intraocular pressure.

Sympathomimetics, monoamine oxidase (MAO) inhibitors and tricyclic antidepressants can enhance the effect of salbutamol.

β2-Agonists potentiate the hypokalemic effect of loop diuretics. Therefore, during joint use, the level of potassium in the blood serum should be checked regularly.

Guaifenesin can potentiate the effects of CNS depressants, as well as ethanol.

α- and non-selective β-adrenoblockers (eg, atenolol, propranolol, oxyprenolol), as well as betahistine weaken the effect of salbutamol, therefore, their simultaneous use is not recommended.

 

Use during pregnancy and lactation

Consult your doctor before starting to take the medicine during pregnancy.

Inform your doctor if you become pregnant during treatment.

If it is necessary to use the drug during lactation, breastfeeding should be temporarily stopped or appropriate contraceptive methods should be used to prevent pregnancy.

 

Effects on the ability to drive vehicles and other potentially dangerous mechanisms

During treatment with the drug, side effects such as headache, dizziness, and drowsiness may be observed. When these reactions occur, patients are not recommended to use vehicles and other types of activities that require special attention and psychomotor reactions.

 

Method of use and dosage

Salbrofen syrup is taken orally 30 minutes after eating.

The preparation can be mixed with water or fruit juice.

Shake the vial before use.

In order to strengthen the effect of the drug, it is recommended to drink enough liquid during the treatment. A measuring cap packed in a box is used for dosing.

Use the following doses unless otherwise prescribed by a doctor.

Use in children under 2 years of age is possible only with a doctor's appointment and supervision.

Children under 6 years: 5 ml (½ measuring cap) 3 times a day

Children aged 6-12 years: 10 ml (1 measuring cap) 3 times a day

Children and adults over 12 years old: 10-20 ml (1-2 measuring caps) 3 times a day

The duration of treatment is determined by the doctor individually, but usually it is 3-7 days.

Do not use the drug for a long time without consulting a doctor.

During long-term reception, the dose should be adjusted by the doctor.

Additional information on special groups of patients

Patients with renal/hepatic insufficiency

It should be used with caution in those with kidney, liver and peptic ulcer disease.

Elderly patients

There are no special instructions for use in elderly patients.

 

Side effects

As with all medicines, unwanted side effects may occur in people who are sensitive to any of the ingredients in the preparation. The drug is usually well received by the body. Side effects rarely lead to treatment discontinuation. Serious adverse reactions are very rare.

Observed additional reactions are classified according to the effect on organ systems as follows:

Respiratory system: exacerbation of asthma, bronchospasm, cough, epistaxis, laryngitis, oropharyngeal irritation and edema, laryngitis, rhinitis.

To the immune system: allergic reactions (facial swelling, shortness of breath, itching), fever.

To the skin and subcutaneous fat tissue: angioneurotic edema, skin rash, urticaria.

To the digestive system: dry mouth, dyspepsia, gastroenteritis, unpleasant taste in the mouth, nausea, vomiting.

Cardiovascular system: angina pectoris, cardiac discomfort, hyperemia, hypo/hypertension, palpitations, tachycardia, arrhythmia, atrial fibrillation.

To the nervous system: dizziness, drowsiness, headache, insomnia, migraine, irritability, alertness, convulsions.

To the musculoskeletal system, connective tissue: muscle spasms, musculoskeletal pain, tremor, weakness.

To the kidneys and urinary tract: pink coloration of urine.

Endocrinological and metabolic disorders: hyperglycemia, hypokalemia, lactic acidosis.

Consult your doctor if unwanted effects occur.

If you experience any side effects not listed in this package insert, tell your doctor.

 

Overdose

Symptoms: headache, tremor, dry mouth, dizziness, fatigue, hypo- and hypertension, palpitations, tachycardia, arrhythmia, hypokalemia, gastrointestinal discomfort, nausea, drowsiness.

Treatment: gastric lavage, administration of activated charcoal, symptomatic and supportive treatment.

 

Release form

Syrup for internal reception.

100 ml of solution in a glass vial. 1 vial and a measuring cap (10 ml) are packed in a cardboard box together with a leaflet.

 

Store condition

It should be stored at a temperature not higher than 25°C, in a dry place, protected from light and out of the reach of children.

 

Shelf life

2 years.

Do not use after the expiration date.

 

Condition of release from pharmacy

It is released on the basis of a prescription.

 

Producer

Opes Healthcare Pvt. Ltd., India.

Trimul Estate, Khatraj, Tal Kalol, Gandhinagar dist, Gujarat, India.

 

Holder of registration card

Tempus LLC, Azerbaijan Republic.

Javadkhan str.5th micro district, H.11,F.60, Nasimi district, AZ1102, Baku city, Azerbaijan.