Bronchoton ambro
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BRONCHOTON AMBRO
Composition:
Active substance: ambroxol hydrochloride;
5 ml of syrup contains ambroxol hydrochloride 15 mg;
Excipients: citric acid monohydrate; sorbitol solution, non-crystallizing (E 420); glycerol; methylparaben (methyl p-hydroxybenzoate) (E 218); propylparaben (propyl p-hydroxybenzoate) (E 216); propylene glycol; strawberry flavoring; purified water.
Pharmaceutical form. Syrup.
Main physicochemical properties: transparent yellowish liquid with a strawberry odor.
Pharmacotherapeutic group. Medicinal products used in cough and common cold conditions. Mucolytic agents. ATC code R05C B06.
Pharmacological Properties
Pharmacodynamics
The active ingredient of Bronchoton ambro syrup, ambroxol hydrochloride, increases the serous fraction of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by directly affecting type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates ciliary activity, thereby reducing sputum viscosity and improving its expulsion (mucociliary clearance). Improvement in mucociliary clearance has been demonstrated in clinical pharmacological studies.
Activation of secretion, reduction in secret viscosity, and improved mucociliary clearance promote mucus elimination and facilitate expectoration of sputum.
In patients with COPD who received prolonged-release capsules of ambroxol hydrochloride 75 mg for 6 months, a significant reduction in the number of exacerbations was observed compared to placebo, starting from the end of the second month of treatment. Patients treated with ambroxol hydrochloride experienced shorter disease duration and required fewer days of antibiotic therapy. Compared to placebo, treatment with prolonged-release ambroxol hydrochloride capsules showed statistically significant improvement in patient outcomes regarding sputum expectoration, cough, dyspnea, and auscultatory findings.
In a rabbit eye model, ambroxol hydrochloride demonstrated a local anesthetic effect, which may be explained by its sodium channel-blocking properties.
In vitro studies have shown that ambroxol hydrochloride blocks voltage-dependent neuronal sodium channels; binding was reversible and concentration-dependent.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces the release of cytokines from mononuclear and polymorphonuclear blood and tissue cells.
In clinical trials involving patients with pharyngitis, significant reduction in throat pain and redness was demonstrated with ambroxol hydrochloride use.
Due to the pharmacological properties of ambroxol, pain relief occurred rapidly during treatment of upper respiratory tract diseases, as observed in clinical efficacy studies of ambroxol inhalation forms.
The use of ambroxol hydrochloride increases the concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. The clinical significance of this effect has not yet been established.
Pharmacokinetics
Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and sufficiently complete, with linear dose dependency within the therapeutic range. Maximum plasma concentrations are reached within 1–2.5 hours after oral administration of immediate-release formulations and on average after 6.5 hours with slow-release formulations.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentration of the active substance found in the lungs. The volume of distribution after oral administration is 552 liters. In plasma, within the therapeutic range, approximately 90% of the drug is protein-bound.
Metabolism and Elimination. Approximately 30% of the dose is eliminated via presystemic metabolism after oral administration. Ambroxol hydrochloride is metabolized primarily in the liver through glucuronidation and degradation to dibromoantranilic acid (approximately 10% of the dose). Studies on human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoantranilic acid.
Within 3 days after oral administration, ambroxol hydrochloride is excreted in urine, with about 6% of the dose excreted unchanged and approximately 26% of the dose excreted as conjugated metabolites.
The elimination half-life of ambroxol hydrochloride is approximately 10 hours. Total clearance is about 660 ml/min, with renal clearance accounting for approximately 8% of total clearance. Within 5 days, approximately 83% of the total dose is excreted in urine.
Pharmacokinetics in Special Patient Populations. In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, resulting in 1.3–2 times higher plasma levels. However, since the therapeutic range of ambroxol hydrochloride is sufficiently wide, dosage adjustment is not required.
Age and gender have no clinically significant effect on the pharmacokinetics of ambroxol hydrochloride; therefore, no dose adjustment is necessary.
Food intake does not affect the bioavailability of ambroxol hydrochloride.
Clinical characteristics.
Indications.
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and weakened mucus clearance.
Contraindications.
Bronhoton ambro, syrup, 15 mg/5 ml, must not be used in patients with known hypersensitivity to ambroxol hydrochloride or to any of the excipients of the medicinal product.
Bronhoton ambro, syrup, 15 mg/5 ml, should be used in children under 2 years of age only under medical supervision.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of Bronhoton ambro, syrup, 15 mg/5 ml, and drugs that suppress cough may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should be used only after careful assessment by a physician of the benefit-risk ratio.
Special precautions for use
Severe skin reactions have been reported, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), associated with the use of ambroxol hydrochloride. If signs of progressive skin rash (sometimes associated with blistering or mucosal involvement) occur, treatment with ambroxol hydrochloride should be discontinued immediately and medical advice should be sought.
Bronhoton ambro, syrup, 15 mg/5 ml, should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia) due to the risk of promoting secretion accumulation.
Patients with impaired renal function or severe hepatic insufficiency should take Bronhoton ambro, syrup, 15 mg/5 ml, only after consultation with a physician. In patients with severe renal insufficiency, administration of ambroxol, like any active substance metabolized in the liver and subsequently excreted by the kidneys, may lead to accumulation of metabolites formed in the liver.
Bronhoton ambro, syrup 15 mg/5 ml, contains 2.25 g of sorbitol in 5 ml (equivalent to 6.75 g with the use of the maximum recommended daily dose of 15 ml). Sorbitol may have a mild laxative effect. The energy value of 1 g of sorbitol is 2.6 kcal. If a patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Preclinical studies have not revealed any direct or indirect harmful effects of the drug on pregnancy, embryonic/foetal development, parturition, or postnatal development.
Due to extensive clinical experience, no adverse effects on the foetus have been observed following administration of ambroxol hydrochloride after the 28th week of pregnancy.
However, usual precautionary measures regarding medication intake during pregnancy should be observed. Bronhoton ambro, syrup, is not recommended during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride is excreted in breast milk. Bronhoton ambro, syrup, is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate a direct or indirect harmful effect on fertility.
Ability to affect reaction speed while driving or operating machinery
There are no data on the effect of the medicinal product on the ability to drive or operate machinery. Studies on the influence on reaction speed while driving or operating machinery have not been conducted.
Method of Administration and Dosage
Unless otherwise indicated, the recommended dosage regimen for Bronhoton ambro, syrup, 15 mg/5 ml, is as follows:
Children under 2 years of age: 2.5 ml (1/2 teaspoon) twice daily (equivalent to 15 mg of ambroxol hydrochloride per day).
Children aged 2–5 years: 2.5 ml (1/2 teaspoon) three times daily (equivalent to 22.5 mg of ambroxol hydrochloride per day).
Children aged 6–12 years: 5 ml (1 teaspoon) 2–3 times daily (equivalent to 30–45 mg of ambroxol hydrochloride per day).
For adults and patients aged 12 years and older, syrup with a higher concentration is recommended (Bronhoton ambro, syrup, 30 mg/5 ml).
Bronhoton ambro, syrup, 15 mg/5 ml, may be taken during or after meals. The dose of Bronhoton ambro, syrup, 15 mg/5 ml, can be measured using the dosing cup provided in the package.
In general, there are no restrictions regarding duration of treatment; however, prolonged therapy should be conducted under medical supervision.
Bronhoton ambro, syrup, 15 mg/5 ml, should not be used for longer than 4–5 days without consulting a physician.
Bronhoton ambro, syrup, 15 mg/5 ml, is alcohol-free.
Children
Bronhoton ambro, syrup, 15 mg/5 ml, can be used in pediatric practice. In children under 2 years of age, it should be administered only on medical advice.
Overdose
There are currently no reports of specific overdose symptoms. Symptoms reported in isolated cases of overdose and/or accidental drug ingestion are consistent with known adverse effects of ambroxol when used at recommended doses and require symptomatic treatment.
Adverse Reactions
Adverse reactions are categorized by frequency as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); not known (cannot be estimated based on available data).
Immune system disorders:
rare – hypersensitivity reactions;
not known – anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.
Skin and subcutaneous tissue disorders:
rare – rash, urticaria;
not known – serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).
Nervous system disorders:
common – dysgeusia (taste disturbance).
Gastrointestinal disorders:
common – nausea, oral hypoesthesia;
uncommon – vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth;
rare – throat dryness;
very rare – hypersalivation.
Respiratory, thoracic and mediastinal disorders:
common – pharyngeal hypoesthesia;
not known – dyspnea (as a hypersensitivity reaction).
General disorders:
uncommon – fever, mucosal reactions.
Transient elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels have been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Shelf life after first opening of the bottle – 28 days.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach and sight of children.
Packaging.
120 ml of syrup in a bottle; 1 bottle with a measuring cup in a cardboard box.
Supply category. Over-the-counter (without prescription).
Manufacturer. VETPROM AD, the Vpharma site / VETPROM AD, the Vpharma site.
Manufacturer's address and location of operations.
26 Otets Paissii Str., Radomir 2400, Republic of Bulgaria.