Ambroxol extra
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROXOL EXTRA (AMBROXOL EXTRA)
Composition:
Active substance: ambroxol hydrochloride;
One tablet contains ambroxol hydrochloride 30 mg;
Excipients: lactose monohydrate; maize starch; colloidal anhydrous silicon dioxide; magnesium stearate.
Pharmaceutical form. Tablets.
Main physicochemical properties: white or white with a creamy tint tablets, flat cylindrical shape, beveled edges, a score line on one side.
Pharmacotherapeutic group.
Preparations used for cough and colds. Mucolytic agents.
ATC code R05C B06.
Pharmacological properties.
Pharmacodynamics.
Preclinical studies have demonstrated that the active substance of the drug Ambroxol Extra, tablets – ambroxol hydrochloride – enhances the production of the serous component of bronchial secretion. Ambroxol increases pulmonary surfactant secretion by directly affecting type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates ciliary activity, thereby reducing sputum viscosity and improving its elimination (mucociliary clearance). Improvement in mucociliary clearance has been confirmed in clinical pharmacological studies.
Enhanced production of serous secretion and improved mucociliary clearance facilitate expectoration and reduce coughing.
In patients with COPD who received ambroxol hydrochloride prolonged-release capsules 75 mg once 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. In patients treated with ambroxol hydrochloride, the duration of illness was significantly shorter, and fewer days of antibiotic therapy were required. These patients also showed a statistically significant reduction in symptoms such as difficulty in expectoration, cough, dyspnea, and auscultatory sounds, compared to placebo.
A local anesthetic effect of ambroxol hydrochloride has been observed in a rabbit eye model, which may be explained by its sodium channel-blocking properties. In vitro studies have shown that ambroxol hydrochloride blocks 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.
Clinical trials involving patients with pharyngitis have demonstrated a significant reduction in throat pain and redness upon using the drug.
Due to the pharmacological properties of ambroxol, pain relief occurred rapidly during treatment of upper respiratory tract disorders, as observed in clinical efficacy studies of ambroxol inhalation forms.
The use of ambroxol hydrochloride increases the concentration of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. However, no clinical significance of this effect has been established to date.
Pharmacokinetics.
Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and complete, with linear dose-dependency within the therapeutic dose range. Maximum plasma concentration is reached within 1–2.5 hours after oral administration of immediate-release dosage forms and on average after 6.5 hours with sustained-release formulations. Absolute bioavailability after a 30 mg tablet dose is 79%.
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 expected volume of distribution after oral administration is 552 L. In plasma, within the therapeutic dose range, approximately 90% of the drug is protein-bound.
Metabolism and elimination. Approximately 30% of the orally administered dose undergoes presystemic metabolism. Ambroxol hydrochloride is primarily metabolized in the liver via glucuronidation and cleavage to dibromoantranilic acid (approximately 10% of the dose). Studies using human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoantranilic acid.
Within 3 days after oral administration, about 6% of the dose is excreted in urine unchanged, and approximately 26% of the dose – as conjugated metabolites.
The elimination half-life from plasma is approximately 10 hours. Total clearance is about 660 mL/min. Renal clearance accounts 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 plasma levels 1.3 to 2 times higher. 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.
Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and impaired mucus clearance.
Contraindications.
Hypersensitivity to ambroxol hydrochloride or to any of the other components of the medicinal product.
Not recommended for children under 6 years of age due to dosage considerations.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of ambroxol and antitussive 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 use.
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 worsening skin rash (sometimes associated with blistering or mucosal involvement) occur, treatment with ambroxol hydrochloride should be immediately discontinued and medical advice sought.
Ambroxol Extra tablets contain lactose. Patients with rare hereditary conditions of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication.
Ambroxol Extra tablets 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 Ambroxol Extra tablets only after consultation with a physician. When ambroxol, like any active substance metabolized in the liver and subsequently excreted by the kidneys, is administered, metabolites formed in the liver may accumulate in patients with severe renal insufficiency.
Use during pregnancy or breastfeeding
Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Animal studies have not revealed any direct or indirect adverse effects on pregnancy, embryonic/fetal development, parturition, or postnatal development.
Studies on the use of the drug after the 28th week of pregnancy have shown no harmful effects on the fetus.
However, usual precautionary measures regarding medication use during pregnancy should be followed. In particular, Ambroxol Extra should not be used during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride is excreted in breast milk; therefore, the drug is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate any direct or indirect adverse effects on fertility.
Ability to affect driving performance and use of machinery
There are no data on the effects of ambroxol on the ability to drive or operate machinery. Specific studies have not been conducted.
Dosage and method of administration.
If not otherwise prescribed, the recommended dose is as follows:
Children aged 6 to 12 years: the usual dose is 1/2 tablet 2–3 times daily (equivalent to 30–45 mg of ambroxol hydrochloride per day).
Adults and children aged 12 years and older: the usual dose is 1 tablet 3 times daily for the first 2–3 days (equivalent to 90 mg of ambroxol hydrochloride per day). Treatment should continue with 1 tablet 2 times 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 taking 2 tablets twice daily (equivalent to 120 mg of ambroxol hydrochloride per day).
The tablets should be swallowed whole with sufficient liquid (e.g., water, tea, or fruit juice) after meals.
In general, there are no restrictions regarding duration of treatment; however, prolonged therapy should be conducted under medical supervision.
The drug should not be used for longer than 4–5 days without consulting a physician.
Children.
For children under 6 years of age, ambroxol in another pharmaceutical form – syrup or solution for inhalation and oral use – is recommended.
Overdose.
Currently, there are no reports of overdose cases in humans. Symptoms reported from isolated cases of overdose and/or medication misuse correspond to the known adverse effects of ambroxol at recommended doses and require symptomatic treatment.
Side effects.
The following classification was used to assess the frequency of adverse reactions:
| very common |
>10 %; |
| common |
>1 % and <10 %; |
| uncommon |
>0.1 % and <1 %; |
| rare |
>0.01 % and <0.1 %; |
| very rare |
<0.01 %; |
| frequency not known |
cannot be estimated from available data. |
Immune system disorders:
Rare: hypersensitivity reactions;
Frequency unknown: anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.
Skin and subcutaneous tissue disorders:
Rare: rash, urticaria;
Frequency unknown: serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).
Gastrointestinal disorders:
Common: nausea;
Uncommon: vomiting, diarrhea, dyspepsia, abdominal pain;
Very rare: hypersalivation.
Respiratory, thoracic and mediastinal disorders:
Frequency unknown: dyspnea (as a hypersensitivity reaction).
General disorders:
Uncommon: pyrexia, mucosal reactions.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions to the State Expert Centre of the Ministry of Health of Ukraine.
Shelf life.
5 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of the reach and sight of children.
Packaging.
10 tablets in a blister; 1, 2, 3 or 4 blisters per cardboard pack.
Supply classification.
Over-the-counter.
Manufacturer.
ASTRAFARM LLC
Manufacturer's address and place of business.
6 Kyivska Street, Vyshneve, Buchanskyi District, Kyiv Oblast, 08132, Ukraine