Abrol® sr

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

Composition:

Active substance: ambroxol hydrochloride;

each prolonged-release capsule contains: ambroxol hydrochloride 75 mg;

Excipients: microcrystalline cellulose, xanthan gum, hypromellose, hydroxypropylcellulose, magnesium stearate, hard gelatin capsule*;

*hard gelatin capsule: gelatin, purified water, titanium dioxide (E 171).

Medicinal form. Prolonged-release capsules.

Main physicochemical properties: opaque capsules with a creamy-white body and a creamy-white cap, containing a white powder.

Pharmacotherapeutic group.

Preparations used in cough and colds. Mucolytic agents.

ATC Code: R05C B06.

Pharmacological properties.

Pharmacodynamics.

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

Enhanced secretion production, reduced viscosity, and improved mucociliary clearance promote expectoration and facilitate coughing up of sputum.

Long-term use (6 months) of ambroxol hydrochloride (in 75 mg oral sustained-release formulation) in patients with COPD led to a significant reduction in exacerbations after a two-month treatment period. In patients receiving ambroxol hydrochloride, duration of illness and antibiotic therapy was significantly shorter. Compared to placebo, treatment with ambroxol hydrochloride 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 ambroxol hydrochloride, potentially explained by sodium channel blocking properties, was observed in a rabbit eye model.

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

Ambroxol hydrochloride demonstrated 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 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 forms.

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

Antiviral properties in vitro and in animal experimental 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 replication of influenza A virus.

Currently, the clinical relevance 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 dose-dependence 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 highly pronounced, with the highest concentration of 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 degradation to dibromoantranilic acid (approximately 10% of the dose). Studies with human liver microsomes showed 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% – as conjugated metabolites.

The elimination half-life from plasma is approximately 10 hours. Total clearance is within the range of 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.

AbrOl®SR is not intended for use in children under 12 years of age due to the amount of active substance contained in the capsule.

Interaction with other medicinal products and other forms of interaction.

When AbrOl®SR is used concomitantly with antitussive agents in patients with existing respiratory disorders 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

Serious 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 lesions) occur, treatment with ambroxol hydrochloride should 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 impairment, 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, embryonal/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 followed. In particular, prolonged-release capsules Abral®SR are not recommended during the first trimester of pregnancy.

Breastfeeding

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

Fertility

Preclinical studies do not indicate a direct or indirect adverse effect on fertility.

Ability to affect reaction speed when driving vehicles or operating machinery

There are no data on the effects of ambroxol on the ability to drive vehicles 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 capsule once daily (equivalent to 75 mg/day of ambroxol hydrochloride), taken in the morning or evening. Abruol®SR may be taken regardless of food intake. The capsules should be swallowed whole with an adequate amount of liquid (water, tea, fruit juice).

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 product must not be administered to children under 12 years of age due to the amount of active substance contained in the capsule. 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 associated with overdose. Symptoms described in isolated reports of overdose and/or accidental drug ingestion correspond to the known adverse reactions of ambroxol hydrochloride when used at recommended doses and require symptomatic treatment.

Side effects

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 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, 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 marketing authorization is of great importance. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to 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.

Keep out of reach and sight of children.

Packaging.

10 capsules per blister. 1 or 2 blisters per cardboard pack.

Authorization category.

Over-the-counter.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's address and location of its business activity.

40020, Ukraine, Sumy region, city of Sumy, Skryabina Street, 54.

or

Manufacturer.

LLC "GLEDPHARM LTD".

Manufacturer's address and location of its business activity.

40020, Ukraine, Sumy region, city of Sumy, Davydovskoho Hryhoriia Street, 54.