Abrol® sr

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

Composition:

Active substance: ambroxol hydrochloride;

One tablet contains 75 mg of ambroxol hydrochloride;

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

Pharmaceutical form. Prolonged-release tablets.

Main physicochemical properties: white, smooth, round biconvex tablets, smooth on both sides.

Pharmacotherapeutic group.

Medicinal products used for cough and common cold. Mucolytic agents.

ATC code R05C B06.

Pharmacological Properties

Pharmacodynamics

The active ingredient of the prolonged-release tablets abroL®SR, ambroxol hydrochloride, increases the serous component of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion through direct action on type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates the activity of cilia of the ciliated epithelium, thereby reducing sputum viscosity and improving its clearance (mucociliary clearance). Improvement in mucociliary clearance has been demonstrated in clinical pharmacological studies.

Enhancement of secretion production, reduction in viscosity, and improved mucociliary clearance promote expectoration and facilitate sputum expulsion.

Long-term use (6 months) of ambroxol hydrochloride (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 ambroxol hydrochloride, the duration of illness and antibiotic therapy was significantly shorter. Compared to placebo, treatment with ambroxol hydrochloride in sustained-release oral formulation showed statistically significant improvement in symptoms related to expectoration difficulties, cough, dyspnea, and auscultatory findings.

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

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

Ambroxol hydrochloride has shown anti-inflammatory effects in vitro. In vitro studies revealed that ambroxol hydrochloride 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 with ambroxol hydrochloride use.

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

After administration of ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) increase in bronchopulmonary secretions and sputum. Currently, no clinical significance has been established for this observation.

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, pretreatment with ambroxol resulted in reduced replication of influenza A virus.

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

Pharmacokinetics

Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and nearly 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 within 6.5 hours with sustained-release formulations.

Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and 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 primarily metabolized in the liver via glucuronidation and cleavage into dibromomethylanthranilic acid (about 10% of the dose). Studies using human liver microsomes showed that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromomethylanthranilic acid.

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

The elimination half-life from plasma is approximately 10 hours. Total clearance is around 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 1.3–2 times higher. 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.

Clinical characteristics.

Indications.

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

Contraindications.

AbrOl®SR must not be used in patients with known hypersensitivity to ambroxol hydrochloride or to any of the excipients of the medicine.

AbrOl®SR, prolonged-release tablets 75 mg, is not intended for use in children under 12 years of age due to the amount of active substance contained in the tablet.

Interaction with other medicinal products and other forms of interaction.

When using AbrOl®SR in combination with antitussive agents in patients with existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis or bronchiectasis, (dangerous) accumulation of secretions 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 lesions) occur, ambroxol hydrochloride treatment must be discontinued immediately and medical advice should be sought.

Abral® SR 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 Abral® SR prolonged-release tablets 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.

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 studies have shown no adverse effects on the fetus following administration of ambroxol hydrochloride after the 28th week of pregnancy.

However, standard precautionary measures regarding medication use during pregnancy should be observed. In particular, Abral® SR tablets are not recommended during the first trimester of pregnancy.

Breastfeeding

Preclinical studies have shown that ambroxol hydrochloride is excreted into breast milk. Abral® SR is not recommended during breastfeeding.

Fertility

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

Ability to influence the reaction rate while driving or operating machinery

There are no data on the effects 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.

If not otherwise prescribed, the recommended dosage regimen for Abruol®SR is as follows.

Adults and children aged 12 years and older: 1 tablet once daily (equivalent to 75 mg/day of ambroxol hydrochloride), taken in the morning or evening after meals. Tablets should be swallowed whole with sufficient amount of water.

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

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

Children.

The drug is not recommended for children under 12 years of age due to the amount of active substance contained in the tablet. For children under 12 years of age, ambroxol in syrup form (15 mg/5 ml or 30 mg/5 ml) is recommended.

Overdose.

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

Side effects

The adverse reactions listed below are classified by system organ class 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 (cannot be estimated from the available data).

Within each group, adverse reactions are listed in decreasing order of 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 reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

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

Gastrointestinal disorders: common – nausea; uncommon – vomiting, diarrhea, dyspepsia, abdominal pain; very rare – hypersalivation; frequency not known – decreased oral sensitivity, dry mouth, dry throat.

Respiratory, thoracic and mediastinal disorders: frequency not known – dyspnea (as a hypersensitivity reaction), dyspnea and bronchospasm, decreased pharyngeal sensitivity.

General disorders: uncommon – pyrexia, mucosal reactions.

Reporting of suspected adverse reactions.

Reporting 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 and patients, as well as 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.

3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 1 or 2 blisters per cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's address and location of its business operations.

54 Skryabina Street, Sumy, Sumy Region, 40020, Ukraine.