SETEGIS

INSTRUCTIONS FOR MEDICAL USE OF AMBROXOL HYDROCHLORIDE

Composition

active substance: ambroxol hydrochloride; 1 tablet contains ambroxol hydrochloride 30 mg; excipients: potato starch, lactose monohydrate, microcrystalline cellulose, colloidal anhydrous silicon dioxide, calcium stearate.

Pharmaceutical Form

Tablets.

Main Physico-Chemical Properties

Tablets are white or white with a yellowish tint.

Pharmacotherapeutic Group

Means used for cough and cold diseases. Mucolytic agents. ATC Code R05C B06.

Pharmacological Properties

Pharmacodynamics

In preclinical studies, it was found that the active substance of the drug - ambroxol hydrochloride - increases the formation of the serous component of bronchial secretions. Ambroxol enhances the release of lung surfactant through a direct effect on type II pneumocytes in the alveoli and Clara cells in the bronchioles, as well as stimulates ciliary activity, resulting in a decrease in mucus viscosity and improvement of its clearance (mucociliary clearance). The increase in mucociliary clearance was confirmed by the results of clinical and pharmacological studies. Enhanced production of serous secretions and increased mucociliary clearance facilitate expectoration and reduce coughing.

In patients with chronic obstructive pulmonary disease who received ambroxol hydrochloride in the form of prolonged-release capsules at a dose of 75 mg for 6 months, a significant decrease in the number of exacerbations was observed at the end of the 2nd month of treatment compared to the placebo group. In patients treated with ambroxol hydrochloride, the disease lasted significantly fewer days, and they needed fewer days of antibiotic therapy. They also observed a statistically significant reduction in symptoms such as difficulty expectorating, coughing, shortness of breath, and auscultatory sounds compared to the placebo group.

A local anesthetic effect of ambroxol hydrochloride was observed in a rabbit eye model, which can be explained by the properties of sodium channel blockade. In vitro studies have shown that ambroxol hydrochloride blocks neuronal sodium channels; binding was reversible and concentration-dependent.

Ambroxol hydrochloride had an anti-inflammatory effect in vitro. Therefore, ambroxol hydrochloride significantly reduces the release of cytokines from mononuclear and polymorphonuclear blood cells and tissues.

In clinical trials involving patients with pharyngitis, a significant reduction in pain and redness in the throat was confirmed when using the drug.

The pharmacological properties of ambroxol hydrochloride, which lead to rapid relief of pain and associated discomfort in the nasal cavity, ear, and trachea when inhaled, correspond to the data of auxiliary observation of symptoms in clinical studies of the effectiveness of ambroxol in the treatment of upper respiratory tract infections.

The use of ambroxol hydrochloride increases the concentration of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. Currently, the clinical significance of this phenomenon has not been established.

Pharmacokinetics

Absorption. The absorption of ambroxol hydrochloride from oral immediate-release forms is rapid and fairly complete, with a linear dependence on the dose in the therapeutic range. The maximum plasma level is reached within 1-2.5 hours when taking oral immediate-release forms and on average within 6.5 hours when using prolonged-release forms.

The absolute bioavailability after taking a 30 mg tablet is 79%.

Distribution. When taken orally, the distribution of ambroxol hydrochloride from blood to tissues is rapid and pronounced, with the highest concentration of the active substance in the lungs. The expected volume of distribution when taken orally is 552 liters. In plasma, within the therapeutic dose range, approximately 90% of the drug is bound to proteins.

Metabolism and Excretion. Approximately 30% of the dose is excreted after oral administration due to presystemic metabolism. Ambroxol hydrochloride is metabolized mainly in the liver by glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). Studies on 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 in the urine in unchanged form, and approximately 26% of the dose is excreted in conjugated form.

The half-life from plasma is approximately 10 hours. The total clearance is approximately 660 ml/min. Renal clearance is approximately 8% of the total. Within 5 days, approximately 83% of the total dose is excreted in the urine.

Pharmacokinetics in Special Patient Groups. In patients with impaired liver function, the excretion of ambroxol hydrochloride is reduced, resulting in a 1.3-2 times higher plasma level. Since the therapeutic range of ambroxol hydrochloride is sufficiently wide, dose adjustment is not required.

Age and sex do not have a clinically significant effect on the pharmacokinetics of ambroxol hydrochloride, so dose adjustment is not necessary.

Food intake does not affect the bioavailability of ambroxol hydrochloride.

Clinical Characteristics

Indications

Secretolytic therapy for acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and weakened mucus transport.

Contraindications

Ambroxol hydrochloride should not be used in patients with known hypersensitivity to ambroxol hydrochloride or other components of the drug.

Ambroxol hydrochloride tablets of 30 mg are not intended for use in children under 12 years of age due to the strength of the drug.

Interactions with Other Medicinal Products and Other Types of Interactions

Concomitant use of Ambroxol Hydrochloride tablets of 30 mg and cough suppressants may lead to excessive accumulation of mucus due to suppression of the cough reflex. Such a combination is only possible after careful evaluation by the doctor of the ratio of expected benefit to possible risk.

Special Warnings and Precautions for Use

There have been reports of severe skin damage: multiform erythema, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis associated with the use of ambroxol hydrochloride. If there are signs of progressive skin rash (sometimes with blistering or mucosal involvement), treatment with ambroxol hydrochloride should be discontinued immediately and medical attention should be sought.

Ambroxol Hydrochloride tablets contain 270.8 mg of lactose in the maximum recommended daily dose (120 mg). Patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Ambroxol Hydrochloride tablets should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in the rare disease primary ciliary dyskinesia) due to the risk of secretory accumulation.

Patients with impaired renal function or severe hepatic insufficiency should take Ambroxol Hydrochloride tablets only after consulting a doctor. When using ambroxol, as with any active substance metabolized in the liver and then excreted by the kidneys, there is an accumulation of metabolites formed in the liver in patients with severe renal insufficiency.

Pregnancy and Breastfeeding

Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Animal studies have not revealed direct or indirect harmful effects on the course of pregnancy, embryonic/fetal development, childbirth, or postnatal development.

As a result of clinical studies, the use of the drug after the 28th week of pregnancy did not reveal any harmful effects on the fetus.

However, it is necessary to follow the usual precautions when taking medications during pregnancy. In particular, the use of Ambroxol Hydrochloride tablets is not recommended during the first trimester of pregnancy.

Breastfeeding. Ambroxol hydrochloride is excreted in breast milk. Ambroxol Hydrochloride tablets are not recommended for use during breastfeeding.

Fertility. Preclinical studies have not revealed a direct or indirect harmful effect on fertility.

Ability to Influence the Speed of Reaction when Driving or Operating Other Mechanisms

There is no data on the effect on the speed of reaction when driving or working with other mechanisms. Relevant studies have not been conducted.

Method of Administration and Dosage

Adults and children over 12 years of age should take 1 tablet 3 times a day for the first 2-3 days (equivalent to 90 mg of ambroxol hydrochloride per day). Treatment should be continued with 1 tablet 2 times a day (equivalent to 60 mg of ambroxol hydrochloride per day).

If necessary, the therapeutic effect for adults and children over 12 years of age can be enhanced by taking 2 tablets 2 times a day (equivalent to 120 mg of ambroxol hydrochloride per day).

Tablets should be swallowed whole with a sufficient amount of liquid (e.g., water, tea, or fruit juice), during meals or independently of meal intake.

In general, there are no restrictions on the duration of use, but long-term therapy should be carried out under medical supervision.

Ambroxol Hydrochloride tablets should not be used for more than 4-5 days without consulting a doctor.

Children

For children over 12 years of age.

Overdose

Currently, there are no reports of overdose cases in humans. Symptoms known from individual reports of overdose and/or cases of incorrect use of the drug correspond to the known side effects of Ambroxol Hydrochloride in recommended doses and require symptomatic treatment.

Side Effects

To assess the frequency of adverse events, the following classification was used:

very often >10%;

often >1% and <10%;

uncommon >0.1% and <1%;

rare >0.01% and <0.1%;

very rare <0.01%;

frequency unknown - cannot be estimated from available data

From the immune system:

rare - hypersensitivity reactions;

frequency unknown - anaphylactic reactions, including anaphylactic shock, angioedema, and itching.

From the skin and subcutaneous tissue:

rare - skin rash, urticaria;

frequency unknown - severe skin adverse reactions (including multiform erythema, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

From the gastrointestinal tract:

often - nausea;

uncommon - vomiting, dyspepsia, abdominal pain, diarrhea;

very rare - hypersalivation.

From the respiratory system, thoracic cavity, and mediastinum:

frequency unknown - dyspnea (as a hypersensitivity reaction).

General disorders:

uncommon - fever, reactions from the mucous membranes.

Reporting of Adverse Reactions after Registration of the Medicinal Product

Reporting of adverse reactions after registration of the medicinal product is of great importance. This allows monitoring the benefit/risk ratio of the use of this medicinal product. Medical and pharmaceutical workers, as well as patients or their authorized representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product through the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf Life

3 years.

Do not use after the expiration date stated on the packaging.

Storage Conditions

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

Store in a place inaccessible to children.

Packaging

10 or 20 tablets in a blister pack. 2 blister packs of 10 or 1 blister pack of 20 in a cardboard box.

Release Category

Over-the-counter.

Manufacturer

PRJSC "Khimfarmzavod "Chervona Zirka" (Red Star Chemical Pharmaceutical Plant).

Manufacturer's Location and Address

Ukraine, 61010, Kharkiv region, city of Kharkiv, Gordeyevskaya street, building 1.

Date of Last Revision