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 contain ambroxol hydrochloride 30 mg;
Excipients: citric acid monohydrate; sorbitol solution, non-crystallizing (E 420); glycerin; methylparaben (methyl p-hydroxybenzoate) (E 218); propylparaben (propyl p-hydroxybenzoate) (E 216); propylene glycol; raspberry flavoring; purified water.
Pharmaceutical form. Syrup.
Main physicochemical properties: clear yellowish liquid with a raspberry odor.
Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytics. ATC code R05C B06.
Pharmacological properties.
Pharmacodynamics.
Preclinical studies have demonstrated that the active substance of the medicinal product Bronhoton ambro, syrup – ambroxol hydrochloride – increases the serous fraction of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by direct action on type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates ciliary activity, thereby reducing sputum viscosity and improving its clearance (mucociliary clearance). Improvement in mucociliary clearance has been confirmed in clinical and pharmacological studies.
Activation of secretion, reduction in secretory viscosity, and improvement in mucociliary clearance promote mucus elimination and facilitate expectoration of sputum.
In patients with COPD who received ambroxol hydrochloride, prolonged-release capsules, 75 mg daily 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 significantly fewer days of illness and required fewer days of antibiotic therapy. Compared to placebo, treatment with ambroxol hydrochloride prolonged-release capsules showed statistically significant improvement in patient symptoms related to 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 showed that ambroxol hydrochloride reversibly and concentration-dependently blocks voltage-gated neuronal sodium channels.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces cytokine release from mononuclear and polymorphonuclear blood and tissue cells.
In clinical trials involving patients with pharyngitis, ambroxol hydrochloride significantly reduced throat pain and redness.
Due to its pharmacological properties, ambroxol rapidly relieves pain during treatment of upper respiratory tract disorders, as observed in clinical efficacy studies of ambroxol inhalation forms.
The use of ambroxol hydrochloride increases antibiotic concentrations (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-dependence 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 mainly in the liver through glucuronidation and cleavage to dibromoantranilic acid (approximately 10% of the dose). Studies with human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoantranilic acid.
After 3 days of 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 sex 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.
Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and impaired mucus clearance.
Contraindications.
Bronhoton ambro, syrup, must not be used in patients with hypersensitivity to ambroxol hydrochloride or to any other components of the medicinal product.
Bronhoton ambro, syrup, 30 mg/5 ml, is not recommended for use in children under 12 years of age.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of Bronhoton ambro, syrup, 30 mg/5 ml, and cough-suppressant agents 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 expected benefit versus the potential risk of treatment.
Special precautions for use
There have been reports of severe skin reactions associated with the use of ambroxol hydrochloride, including: erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). If signs of worsening 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 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 only after consultation with a physician. In patients with severe renal insufficiency, administration of ambroxol — as with 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 30 mg/5 ml contains 2.25 g of sorbitol in 5 ml (equivalent to 9.00 g when using the maximum recommended daily dose of 20 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/fetal development, parturition, or postnatal development.
Based on extensive clinical experience, no adverse effects on the fetus have been observed when the drug is used after the 28th week of pregnancy. However, usual precautionary measures regarding medication use during pregnancy should be observed. Bronhoton AmBro syrup 30 mg/5 ml is not recommended during the first trimester of pregnancy. Use during later stages of pregnancy is possible only under medical supervision.
Breastfeeding. Ambroxol hydrochloride passes into breast milk. Bronhoton AmBro syrup is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate any direct or indirect harmful effects on fertility.
Ability to affect reaction speed when 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 effect on reaction speed during driving or operating machinery have not been conducted.
Method of administration and dosage.
If not otherwise indicated, the recommended dosage regimen for Bronchoton ambro, syrup, 30 mg/5 ml is as follows:
Adults and children aged 12 years and older: the usual dose is 5 ml three times daily (equivalent to 90 mg of ambroxol hydrochloride per day) for the first 2–3 days, followed by 5 ml twice daily (equivalent to 60 mg of ambroxol hydrochloride per day).
If necessary, the therapeutic effect in adults and children aged 12 years and older may be enhanced by increasing the dose to 10 ml twice daily (equivalent to 120 mg of ambroxol hydrochloride per day).
Bronchoton ambro, syrup, 30 mg/5 ml can be taken during or after meals. The dose of Bronchoton ambro syrup can be measured using the dosing cup provided in the package. In general, there are no restrictions regarding duration of use; however, prolonged therapy should be conducted under medical supervision.
Bronchoton ambro, syrup, 30 mg/5 ml should not be used for longer than 4–5 days without consulting a physician.
Bronchoton ambro, syrup, 30 mg/5 ml does not contain alcohol.
Children.
Bronchoton ambro, syrup, 30 mg/5 ml may be used in children aged 12 years and older.
Overdose.
There are currently no reports of specific symptoms of overdose. Symptoms reported from isolated cases of overdose and/or accidental ingestion correspond to the known adverse effects of ambroxol 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 from available data).
Immune system disorders:
Rare – hypersensitivity reactions;
Not known – anaphylactic reactions, including anaphylactic shock, angioneurotic edema, 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 – pyrexia, 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 should 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 the reach and sight of children.
Packaging.
120 ml of syrup in a bottle; 1 bottle with a measuring cup in a cardboard box.
Availability category. Over-the-counter.
Manufacturer. VETPROM AD, the Vpharma site.
Manufacturer's address and location of its business operations.
26 Otets Paisiy Str., Radomir 2400, Republic of Bulgaria.