Abrol®

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

Composition:

Active substance: ambroxol hydrochloride;

5 ml of syrup contain 30 mg of ambroxol hydrochloride;

Excipients: hydroxyethylcellulose, sorbitol solution (sorbitol E 420), glycerol, sodium saccharin, benzoic acid (E 210), propylene glycol, flavouring "Apricot", flavouring "Garden Mint", purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear syrup ranging from colourless to slightly yellow.

Pharmacotherapeutic group.

Medicinal products used in cough and colds. Mucolytic agents.

ATC code R05C B06.

Pharmacological Properties

Pharmacodynamics

The active ingredient of Abrol® syrup, ambroxol hydrochloride, increases the serous component of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by directly acting on type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates the activity of ciliary epithelium, thereby reducing sputum viscosity and improving its clearance (mucociliary clearance). Improvement in mucociliary clearance has been demonstrated in clinical and pharmacological studies.

Enhanced secretion production, reduced viscosity, and improved mucociliary clearance promote expectoration and facilitate sputum expulsion.

Long-term use (6 months) of ambroxol hydrochloride (75 mg prolonged-release capsules) in patients with chronic obstructive pulmonary disease resulted in a significant reduction in exacerbations after two months of treatment. In patients receiving ambroxol hydrochloride, the duration of illness and antibiotic therapy was significantly shorter. Compared to placebo, treatment with ambroxol hydrochloride prolonged-release capsules showed statistically significant improvement in symptoms related to expectoration difficulties, cough, dyspnea, and auscultatory findings.

The local anesthetic effect of ambroxol hydrochloride, potentially attributable to sodium channel blocking properties, has been observed in a rabbit eye model.

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 cytokine release 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 the use of 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.

After administration of ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum increase. To date, the clinical significance of this effect has not 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 mouse respiratory model, prior administration of ambroxol resulted in reduced replication of influenza A virus.

At present, the clinical significance of this effect has not been confirmed.

Pharmacokinetics

Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and sufficiently complete, with linear dependence within the therapeutic 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 slow-release formulations.

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

Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and markedly pronounced, with the highest concentration of the active substance found in the lungs. The volume of distribution after oral administration is 552 L. 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 cleavage to dibromanthranilic acid (approximately 10% of the dose). Clinical studies using human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid.

Within 3 days of oral administration, about 6% of the dose is excreted unchanged, while approximately 26% of the dose – is excreted in conjugated form in urine.

The plasma elimination half-life is approximately 10 hours. Total clearance is approximately 660 mL/min. Renal clearance accounts for approximately 8% of total clearance. After 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, so 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 reduced mucus clearance.

Contraindications.

Abral®, syrup, 30 mg/5 ml must not be used in patients with hypersensitivity to ambroxol hydrochloride or to any of the other components of the medicinal product.

Abral®, syrup, 30 mg/5 ml should be used in children under 2 years of age only on medical advice.

Interaction with other medicinal products and other forms of interaction.

When using Abral**®**, syrup, 30 mg/5 ml in combination with antitussive agents in patients with existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis or bronchiectasis, accumulation of secretions (potentially 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 signs of progressive skin rash (sometimes associated with blistering or mucosal involvement) occur, ambroxol hydrochloride treatment must be discontinued immediately and medical advice should be sought.

Abron**®**, syrup, 30 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 impairment should take Abron**®**, syrup, 30 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.

Excipients.

If known intolerance to certain sugars has been diagnosed, consult a physician 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 on pregnancy, embryonal/fetal development, parturition, or postnatal development.

Clinical studies have shown no adverse effects on the fetus when the drug was used after the 28th week of pregnancy.

Nevertheless, usual precautionary measures regarding medication use during pregnancy should be observed. In particular, Abron**®**, syrup, 30 mg/5 ml is not recommended during the first trimester of pregnancy.

Breastfeeding.

Ambroxol hydrochloride is excreted in breast milk. Abron**®**, syrup, 30 mg/5 ml is not recommended during breastfeeding.

Fertility.

Preclinical studies do not indicate any direct or indirect harmful effects on fertility.

Ability to influence the reaction rate when driving or operating machinery.

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

Method of Administration and Dosage

Unless otherwise prescribed, the recommended dosage of ABRol® syrup, 30 mg/5 ml, is as follows:

Children under 2 years of age: 1.25* ml twice daily (equivalent to 15 mg of ambroxol hydrochloride per day);

*To measure the 1.25 ml syrup dose, use the disposable plastic syringe without needle, with a capacity of 2 ml.

Children aged 2–5 years: 1.25* ml three times daily (equivalent to 22.5 mg of ambroxol hydrochloride per day);

*To measure the 1.25 ml syrup dose, use the disposable plastic syringe without needle, with a capacity of 2 ml.

Children aged 6–12 years: 2.5 ml up to three times daily (equivalent to 30–45 mg of ambroxol hydrochloride per day);

Adults and adolescents 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 adolescents 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).

ABRol® syrup, 30 mg/5 ml, can be administered regardless of food intake. The dose of ABRol® syrup, 30 mg/5 ml, should be measured using the dosing cup provided.

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

ABRol® syrup, 30 mg/5 ml, should not be used for longer than 4–5 days without consulting a physician.

ABRol® syrup, 30 mg/5 ml, is suitable for use in patients with diabetes mellitus; 5 ml contains 1.225 g of carbohydrates.

ABRol® syrup, 30 mg/5 ml, does not contain alcohol.

Children

The product may be used in pediatric practice. For children under 2 years of age, use only as directed by a physician.

Overdose

There have been no reports of specific symptoms of overdose. Symptoms reported in isolated cases of overdose and/or accidental ingestion correspond to the known adverse reactions associated with ambroxol hydrochloride when used at recommended doses and require symptomatic treatment.

Adverse Reactions.

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

very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000, including isolated cases), frequency not known (frequency cannot be estimated from 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, and acute generalized exanthematous pustulosis).

Nervous system disorders: common – dysgeusia (taste disturbance).

Gastrointestinal disorders: common – nausea, oral hypoaesthesia; uncommon – vomiting, diarrhoea, dyspepsia, abdominal pain, dry mouth; rare – throat dryness; very rare – hypersalivation.

Respiratory, thoracic and mediastinal disorders: common – pharyngeal hypoaesthesia; frequency not known – dyspnoea (as a symptom of hypersensitivity reaction), dyspnoea and bronchospasm.

General disorders: uncommon – pyrexia, mucosal reactions.

Reporting of suspected adverse reactions.

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

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

After first opening of the bottle, the product should not be stored for longer than 6 months.

Packaging.

100 ml in polyethylene or glass bottles. Each bottle comes in a cardboard box with a measuring cup.

Availability.

Over-the-counter.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's location and address of the place of business activity.

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

or

Manufacturer.

LLC "GLEDFARM LTD".

Manufacturer's location and address of the place of business activity.

40020, Ukraine, Sumy Oblast, Sumy, Hryhoriya Davydovskoho St., 54.