Abrol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ABRол® (ABROL®)

Composition:

Active substance: ambroxol hydrochloride (ambroxol hydrochloride);

One tablet contains ambroxol hydrochloride 30 mg;

Excipients: colloidal anhydrous silicon dioxide, sodium croscarmellose, microcrystalline cellulose, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, round tablets with a score line on one side.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. ATC code R05C B06.

Pharmacological Properties.

Pharmacodynamics.

Hydrochloride ambroxol is a substituted benzylamine and a metabolite of bromhexine. It has been demonstrated that hydrochloride ambroxol enhances the production of the serous component of bronchial secretion and stimulates pulmonary surfactant release by directly affecting type II pneumocytes in alveoli and Clara cells in bronchioles. Additionally, hydrochloride ambroxol stimulates ciliary activity, thereby reducing sputum viscosity and improving its expulsion (mucociliary clearance). Improved mucociliary clearance has been confirmed in clinical and pharmacological studies.

Enhanced serous secretion production and enhanced mucociliary clearance facilitate expectoration and reduce coughing.

Long-term use (6 months) of hydrochloride ambroxol (in 75 mg oral sustained-release formulation) in patients with COPD resulted in a significant reduction in exacerbations after a two-month treatment period. In patients receiving hydrochloride ambroxol, duration of illness and antibiotic therapy was significantly shorter. Compared to placebo, treatment with hydrochloride ambroxol in oral sustained-release formulation showed statistically significant improvement in symptoms related to expectoration difficulties, cough, dyspnea, and auscultatory findings.

The local anesthetic effect of hydrochloride ambroxol, which may be explained by sodium channel blocking properties, was observed in a rabbit eye model.

In vitro studies showed that hydrochloride ambroxol blocks neuronal sodium channels; binding was reversible and concentration-dependent.

Hydrochloride ambroxol has demonstrated anti-inflammatory effects in vitro. Thus, hydrochloride ambroxol significantly reduces cytokine release from mononuclear and polymorphonuclear blood and tissue cells.

Clinical trials involving patients with pharyngitis demonstrated a significant reduction in throat pain and redness upon administration of the drug.

Due to the pharmacological properties of ambroxol, pain relief during treatment of upper respiratory tract disorders was rapidly achieved, as observed in clinical efficacy studies of ambroxol inhalation formulations.

Administration of hydrochloride ambroxol increases concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. To date, no clinical significance of this fact has been established.

Antiviral properties in vitro and in experimental animal models

In vitro studies on human tracheal epithelial cells showed reduced rhinovirus (RV 14) replication. In a murine respiratory model, prior administration of ambroxol resulted in reduced influenza A virus replication.

To date, the clinical significance of this effect has not been confirmed.

Pharmacokinetics.

Absorption. Absorption of hydrochloride ambroxol from immediate-release oral formulations is rapid and complete, with linear dose dependency within the therapeutic range. Maximum plasma concentration is reached within 1–2.5 hours after oral administration of immediate-release formulations and on average after 6.5 hours with sustained-release formulations.

Absolute bioavailability after administration of a 30 mg tablet is 79%.

Distribution. After oral administration, distribution of hydrochloride ambroxol 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 dose is eliminated via presystemic metabolism after oral administration. Hydrochloride ambroxol is metabolized primarily in the liver through glucuronidation and cleavage into dibromoaniline acid (approximately 10% of the dose). Metabolism of hydrochloride ambroxol to dibromoaniline acid involves CYP3A4. Within 3 days of oral administration, about 6% of the dose is excreted in urine unchanged, and approximately 26% of the dose – in conjugated form.

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 groups. In patients with impaired liver function, elimination of hydrochloride ambroxol is reduced, resulting in plasma levels 1.3–2 times higher. However, since the therapeutic range of hydrochloride ambroxol is sufficiently wide, dosage adjustment is not required.

Age and sex have no clinically significant effect on the pharmacokinetics of hydrochloride ambroxol; therefore, no dose adjustment is necessary.

Food intake does not affect the bioavailability of hydrochloride ambroxol.

Clinical characteristics.

Indications.

Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and reduced mucus clearance.

Contraindications.

Abral®, tablets must not be administered to patients with known hypersensitivity to ambroxol hydrochloride or to any of the excipients of the product.

Abral®, tablets are not intended for use in children under 6 years of age. For children under 6 years of age, ambroxol in an appropriate dosage form is recommended.

Interaction with other medicinal products and other forms of interaction.

When using Ambroxol, 30 mg tablets in combination with antitussive agents in patients with existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis or bronchiectasis, accumulation of secretions (which may be dangerous) may occur due to suppression of the cough reflex.

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 symptoms or signs of progressive skin rash (sometimes associated with blistering or mucosal involvement) occur, ambroxol hydrochloride treatment should be discontinued immediately and medical advice sought.

Abron® 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 Abron® tablets only after consultation with a physician. When ambroxol hydrochloride, 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 impairment.

Excipients

This medicinal product contains sodium in the amount of 0.0065 mmol (or 0.15 mg) per tablet, i.e. practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Preclinical studies have not revealed any direct or indirect harmful effects on pregnancy, embryonic/fetal development, parturition, or postnatal development.

Clinical data on the use of ambroxol hydrochloride after the 28th week of pregnancy have shown no adverse effects on the fetus. However, usual precautionary measures regarding medication use during pregnancy should be observed. Particularly during the first trimester of pregnancy, the use of Abron® tablets is not recommended.

Breastfeeding. Ambroxol hydrochloride passes into breast milk. Abron® tablets are not recommended during breastfeeding.

Fertility. Preclinical studies do not indicate a direct or indirect harmful effect of ambroxol hydrochloride on fertility.

Ability to influence the speed of reaction when driving or operating machinery

There are no data on the effect on the ability to drive or operate machinery. Studies on the influence of ambroxol hydrochloride on the speed of reaction when driving or operating machinery have not been conducted.

Method of Administration and Dosage.

If not otherwise prescribed, the recommended dosage of Abrol® tablets 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 administering 2 tablets 2 times 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), regardless of food intake.

In general, there are no restrictions regarding duration of use; however, prolonged therapy should be conducted under medical supervision.

Abrol® tablets should not be used for longer than 4–5 days without consulting a physician.

Children.

For use in children aged 6 years and older who cannot tolerate syrup or solution for inhalation and oral use.

Overdose.

There are currently no reports of cases of overdose. Symptoms reported in isolated cases of overdose and/or medication errors correspond to the known adverse effects of ambroxol hydrochloride at recommended doses and require symptomatic treatment.

Adverse Reactions

The adverse reactions listed below are categorized by organ systems and frequency:

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, including isolated cases), frequency not known (cannot be estimated from the available data).

Within each group, adverse reactions are listed in order of decreasing severity.

Immune system disorders: rare – hypersensitivity reactions; frequency not known – anaphylactic reactions, including anaphylactic shock, angioedema, pruritus.

Skin and subcutaneous tissue disorders: rare – rash, urticaria; frequency not known – serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute generalized exanthematous pustulosis).

Nervous system disorders: frequency not known – dysgeusia (taste disturbance).

Gastrointestinal disorders: common – nausea; uncommon – vomiting, diarrhoea, dyspepsia, abdominal pain; very rare – hypersalivation; frequency not known – oral hypoesthesia, dry mouth, dry throat, heartburn, constipation.

Respiratory, thoracic and mediastinal disorders: frequency not known – dyspnoea (as a symptom of hypersensitivity reaction), rhinorrhoea, dryness of respiratory tract, pharyngeal hypoesthesia, dyspnoea and bronchospasm.

Renal and urinary disorders: frequency not known – dysuria.

General disorders: uncommon – pyrexia, mucosal reactions.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 2 blisters in a cardboard pack.

Supply category.

Over-the-counter (without prescription).

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's address and location of business activity.

40020, Ukraine, Sumy region, Sumy, Skryabina St., 54.

or

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business activity.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.

or

Manufacturer.

LLC "GLEDFARM LTD".

Manufacturer's address and location of business activity.

40020, Ukraine, Sumy region, Sumy, Davydovskoho Hryhorii St., 54.