International non-proprietary name: Ambroxol hydrochloride, Terbutaline sulfate, Guaifenesin

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Composition

Active ingredients: 5 ml of syrup contains 15 mg of ambroxol hydrochloride, 1.25 mg of terbutaline sulfate,

Contains 50 mg of guaifenesin.

Excipients: levomenthol, sodium citrate, anhydrous citric acid, sodium benzoate, macrogol

(polyethylene glycol 400), aspartame, sucralose, propylene glycol, hypromellose (HPMC 5

CPS), Ponso 4R dye (Supra), strawberry flavoring, purified water.

Description

It is a light pink transparent solution.

 

Pharmacotherapeutic group

Combined expectorant drugs (except for combination with antitussive drugs).

ATC code:R05CB06.

 

pharmacological properties

Pharmacodynamics

In some diseases of the respiratory tract, the thick and sticky sputum prevents its removal, which causes coughing and difficulty breathing.

Terbrofen syrup is a combined broncholytic (bronchodilator), mucolytic, expectorant and antiallergic drug used in coughs and colds. The therapeutic effect of the drug is related to the pharmacological properties of its components.

Terbrofen syrup increases the serous component of bronchial secretion, reduces the viscosity of sputum, activates the ciliated epithelium and facilitates the excretion of sputum. Also, it expands the bronchi, increases the permeability of the respiratory tract, makes breathing easier.

Ambroxol hydrochloride is a drug belonging to the benzylamine group, an active N-demethylated metabolite of bromhexine, with mucokinetic, mucolytic and expectorant effects. By breaking down acid mucoproteins, it reduces the viscosity and density of tracheobronchial secretion (mucus in the respiratory tract), dilutes sputum and normalizes its secretion. It relieves cough by softening phlegm. By stimulating type II pneumocytes in the lungs (alveoli), Klar cells in the bronchioles, it increases the production of endogenous surfactant (surfactant), prevents its dispersion and ensures the stability of alveolar cells in the respiratory process. Ambroxol ensures normal motor activity of cilia and easy removal of sputum from the respiratory tract (mucociliary clearance).

Thus, ambroxol reduces tension during coughing and coughing, eliminates respiratory disorders, and facilitates breathing.

Terbutaline sulfate is an adrenomimetic agent that selectively stimulates β2-adrenoreceptors of the bronchi, increases the activity of adenylate cyclase, stabilizes cyclic AMF, reduces the intracellular concentration of calcium, relieves muscle spasm and reduces tone, expands the airways and facilitates breathing. It reduces the viscosity of bronchial mucus, increases mucociliary clearance, reduces edema of the mucous membrane of the bronchi. Also, it stabilizes the membranes of barrier cells, inhibits the release of allergy mediators (serotonin, histamine, etc.) and has an antiallergic effect.

Guaifenesin is a semisynthetic drug belonging to the group of mucolytic and expectorant drugs. The effect is related to the reduction of the surface tension of the bronchial lungs and the adhesive ability of the sputum (sticking to the mucous membrane of the bronchi). Guaifenesin stimulates the receptors of the mucous membrane of the bronchi and the secretory cells that produce neutral polysaccharides, breaks down acidic mucopolysaccharides, increases the secretion of mucous glands of the respiratory tract, increases the volume and reduces the thickness of sputum in the trachea and bronchi, and has a mucolytic effect. Strengthens the effect of the ciliary apparatus of the bronchi, also increases the effectiveness of the cough reflex and facilitates the removal 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

Ambroxol hydrochloride

After reception, it is quickly and completely absorbed in the body. Bioabsorption is 70-80%. When taken on an empty stomach, it reaches the maximum plasma concentration (Cmax) in 0.5-3 hours (average 2 hours). The therapeutic effect of Ambroxol begins 30 minutes after oral administration and lasts for 6-12 hours. Its combination with plasma proteins is 90%.

It accumulates in the lung tissue in the highest concentrations. It passes through the hematoencephalic and placental barriers and is also detected in breast milk. During the "first pass" in the liver, ⅓ is metabolized.

It is excreted by the kidneys in the form of dibromoanthranilic acid and glucuronide metabolites (85%) and unchanged (5-6%). The elimination half-life (t½) is approximately 7-12 hours.

Terbutaline sulfate

Bioabsorption after oral administration is 30-50%. Terbutaline passes through the placenta and penetrates into breast milk. t½ – 16-20 hours. In the liver, it undergoes partial metabolism with the formation of mainly inactive sulfate and glucuronide conjugate metabolites. It is excreted from the body with urine.

Guaifenesin

It is quickly absorbed from the gastrointestinal tract (25-30 minutes after ingestion). Penetrates into tissues containing acidic mucopolysaccharides. It is metabolized by oxidation and demethylation in the liver. t½ is 1 hours. It is removed from the lungs (sputum) and kidneys in the form of both unchanged and inactive metabolites.

 

Instructions for use

Symptomatic treatment of cough accompanied by bronchospasm: tracheobronchitis, obstructive bronchitis, bronchial asthma. 

Treatment of acute and chronic diseases of the respiratory tract accompanied by a violation of sputum secretion and excretion: chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary emphysema, bronchiectasis, pulmonary tuberculosis, pneumoconiosis, sinusitis.

Complex therapy of acute respiratory diseases.

 

Contraindications

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

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

Patients with ischemic heart disease or risk factors for CVD.

Disruption of heart rhythm (arrhythmia).

Severe liver and kidney failure.

Decompensated diabetes.

Bleeding tendency.

The first trimester of pregnancy.

Lactation period.

 

Special instructions and precautions

As with other sympathomimetic drugs, the drug should be prescribed with caution in diabetes, hyperthyroidism, high blood pressure, and severe diseases of the cardiovascular system (aortic stenosis, myocarditis, tendency to prolong the QT interval, heart failure).

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

It can be used in children under 2 years of age only with the appointment and supervision of a doctor.

Guaifenesin can be used only under the prescription and strict supervision of a doctor in case of persistent or chronic cough (for example, smoking, bronchial asthma, emphysema, chronic bronchitis) or cough accompanied by excessive sputum secretion.

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

Because of the hyperglycemic effects of terbutaline, initial monitoring of blood glucose levels is recommended in patients with diabetes.

 

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, Terbrofen syrup should not be used simultaneously with these drugs.

Ambroxol accelerates the absorption of antibacterial agents (ampicillin, amoxacillin, erythromycin, cephalexin, oxytetracycline, sulfonamides) and improves their penetration into the respiratory tract.

Ambroxol should not be prescribed together with potassium antagonists. 

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

Guaifenesin enhances the effect of CNS depressants, as well as ethanol.

Tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, adrenaline and other sympathomimetics can increase the side effects of terbutaline on the cardiovascular system. Terbrofen syrup should be taken at least 2 weeks after the end of taking MAO inhibitors.

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.

Non-selective β-adrenoblockers (atenolol, propranolol, oxyprenolol) weaken the effect of terbutaline, so they should not be used simultaneously.

 

Use during pregnancy and lactation

Due to the lack of sufficient clinical studies, it is not recommended to use it in the I trimester of pregnancy or in cases of suspected pregnancy. In the II and III trimesters of pregnancy, it can be determined after assessing the benefit/risk ratio.

Inform your doctor if you become pregnant during treatment.

There is information on the excretion of the drug in breast milk. 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

Terbrofen syrup is taken orally 30 minutes after a meal. Shake the vial before use. The preparation can be mixed with water or fruit juice.

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.

Children aged 0-6 years: 5-10 ml (½-1 measuring cap) 2-3 times a day

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

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.

Pediatric patients

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

Elderly patients

There are no special instructions for use in elderly patients.

 

Side effects

As with all medicines, there may be unwanted side effects in people who are sensitive to any of the ingredients in the preparation. The drug is usually well received by the body. Side effects are usually mild and disappear when the drug is stopped. Serious adverse reactions are very rare.

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

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

To the skin and subcutaneous tissue: Uvra.

To the nervous system: dizziness, headache, nervousness, tremor, drowsiness, taste disturbance.

Cardiovascular system: tachycardia (palpitations), sweating, tremors.

To the digestive system: nausea, vomiting, dyspepsia, gastralgia, abdominal pain, diarrhea, dryness in the mouth or throat, feeling of chewing in the mouth.

To the musculoskeletal system and connective tissue: muscle spasm.

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

Laboratory indicators: transient increase in serum aminotransferase levels, hyperglycemia, hypokalemia.

Consult your doctor if unwanted effects occur.

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

 

Overdose

Symptoms: nausea, gastrointestinal discomfort, headache, restlessness, tachycardia, arrhythmia, drowsiness, tremor, impaired consciousness, convulsions, hyperglycemia, hypokalemia.

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

 

Release form

Syrup for internal administration, 100 ml, in a yellow glass vial with a twist cap.

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, dry, protected from light and out of the reach of children.

 

Shelf life

3 years.

Do not use after the expiration date.

 

Condition of release from pharmacy

It is released without a prescription.

 

Producer

Opes Healthcare Pvt. Ltd., India.

G-203, Shri kabir Enclave, OPP. Homeopathic college, Bopal Ghuma Road, Ghuam, Ahmedabad-380058, Gujarat.

 

Holder of registration card

NES GROUP LLC, Azerbaijan.

AZ1052, Baku city, Narimanov r., A. Nematulla, house 70A, m.4.