Ambroxol-zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROXOL-ZDOROV'YA (AMBROXOL-ZDOROVYE)

Composition:

Active ingredient: ambroxol;

2 ml (50 drops) of the preparation contain ambroxol hydrochloride 15 mg;

Excipients: citric acid, sodium hydrogen phosphate, sodium chloride, benzalkonium chloride, purified water.

Pharmaceutical form. Solution for inhalation and oral use.

Main physicochemical properties: clear, colorless or slightly yellowish solution.

Pharmacotherapeutic group.

Medicinal products used for cough and colds. Mucolytic agents.

ATC code R05C B06.

Pharmacological properties.

Pharmacodynamics.

Hydrochloride of ambroxol, a substituted benzylamine, is a metabolite of bromhexine. It differs from bromhexine by the absence of a methyl group and the presence of a hydroxyl group in the para-trans position of the cyclohexyl ring.

Studies demonstrate its secretolytic and secretomotor effects in the bronchial tract.

After oral administration, the effect begins on average within 30 minutes and lasts 6–12 hours, depending on the individual dose.

Preclinical studies have shown that ambroxol hydrochloride increases the serous component of bronchial secretion. Ambroxol enhances mucus clearance by reducing viscosity and activating the ciliary epithelium.

Ambroxol activates the surfactant system through a direct effect on type II pneumocytes in alveoli and Clara cells in the region of small airways. It stimulates the formation and release of surfactant material in alveoli and bronchial tree of both fetus and adult. These effects have been demonstrated in various biological species using cell cultures and in vivo.

Moreover, antioxidant effects of ambroxol have been demonstrated in various preclinical studies.

Pharmacokinetics.

Absorption

Ambroxol is almost completely absorbed after oral administration. Tmax after oral intake ranges from 1 to 3 hours. Absolute bioavailability of ambroxol after oral administration is reduced by approximately one-third due to presystemic metabolism.

Distribution

Approximately 85% (80–90%) of the drug is bound to plasma proteins. In lung tissue, ambroxol reaches higher concentrations than in plasma after parenteral administration. Ambroxol can penetrate into cerebrospinal fluid, cross the placental barrier, and is excreted in breast milk.

Biotransformation

Formation of metabolites capable of entering the kidneys (e.g., dibromanilic acid, glucuronide) occurs in the liver.

Elimination

Approximately 90% of the drug is excreted by the kidneys as metabolites formed in the liver. Less than 10% of ambroxol is excreted unchanged by the kidneys. Due to the high degree of protein binding, large volume of distribution, and slow redistribution of the drug from tissues into blood, significant elimination of ambroxol by dialysis or forced diuresis is unlikely.

Terminal half-life from plasma is 7–12 hours. The elimination half-life of ambroxol and its metabolites from plasma is approximately 22 hours.

Patients with hepatic and renal impairment

In patients with severe liver dysfunction, ambroxol clearance is reduced by 20–40%. In patients with severe renal impairment, accumulation of ambroxol metabolites may occur.

Clinical characteristics.

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

Contraindications.

Do not use in patients with hypersensitivity to ambroxol hydrochloride or to other components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of this medicinal product with antitussive agents may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should only be considered after careful evaluation by a physician of the expected benefit versus the potential risk of use.

Concomitant administration of ambroxol with antibiotics (amoxicillin, cefuroxime, doxycycline, and erythromycin) results in higher concentrations of antibiotics in bronchopulmonary secretions and sputum.

Special precautions for use

The product contains benzalkonium chloride as a preservative. When inhaled, benzalkonium chloride may cause bronchospasm.

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

The product 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 secretion accumulation.

Patients with renal impairment or severe hepatic insufficiency should take the product only after consultation with a physician. When ambroxol is used, as with any active substance metabolized in the liver and subsequently excreted by the kidneys, metabolites formed in the liver may accumulate in patients with severe renal insufficiency.

The product contains 42.8 mg of sodium in the recommended daily dose. This should be taken into account by patients on a controlled sodium diet.

Use during pregnancy or breastfeeding.

Pregnancy. Ambroxol hydrochloride crosses the placental barrier.

Clinical studies have shown no adverse effects on the fetus or course of pregnancy when the product is used after the 28th week of gestation. Animal studies have not revealed any direct or indirect harmful effects on pregnancy, embryonal/fetal development, parturition, or postnatal development. However, usual precautions regarding medication intake during pregnancy should be observed. In particular, the use of the product is not recommended during the first trimester of pregnancy.

Breastfeeding period. Ambroxol hydrochloride passes into breast milk. The product is not recommended during breastfeeding.

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

Ability to influence reaction speed when driving vehicles or operating machinery.

There are no data on the effect of the medicinal product on reaction speed when driving vehicles or operating machinery. Studies on the effect on reaction speed when driving vehicles or operating machinery have not been conducted.

Dosage and Administration

1 ml of oral and inhalation solution = 25 drops.

Inhalation Solution

Adults and children aged 6 years and older: 1–2 inhalations of 2–3 ml of solution per day.

Children under 6 years of age: 1–2 inhalations of 2 ml of solution per day.

The product can be used with all modern inhalation devices (except steam inhalers).

It should be diluted in a 1:1 ratio with physiological saline to ensure optimal humidification of the air released by the device.

Do not mix with cromoglicic acid. It should also not be mixed with other solutions whose mixture results in a pH exceeding 6.3, for example, with alkaline inhalation salt (Emser Salt). An increase in pH may lead to precipitation of the free base of ambroxol hydrochloride or clouding of the solution.

The inhalation solution is generally recommended to be warmed to body temperature before starting inhalation.

If only one daily inhalation is possible, an additional orally administered medicinal product should be used.

Since the inhalation process itself may provoke coughing, patients are advised to breathe normally during inhalation.

Patients with bronchial asthma should use bronchodilators prior to inhalation to open the airways.

Oral Solution

Adults and children aged 12 years and older: 4 ml three times daily during the first 2–3 days, equivalent to 90 mg of ambroxol per day; thereafter, 2 ml three times daily, equivalent to 45 mg of ambroxol per day. The dosage of 4 ml three times daily may be continued after consultation with a physician.

• Children aged 6–12 years: 2 ml two to three times daily, equivalent to 30–45 mg of ambroxol per day.
• Children aged 2 to 6 years: 1 ml (25 drops) three times daily, equivalent to 22.5 mg of ambroxol per day.
• Children under 2 years of age: 1 ml (25 drops) two times daily, equivalent to 15 mg of ambroxol per day.

Dosing in patients with renal and/or hepatic impairment

In patients with severe renal or severe hepatic impairment, the product should be administered only after consultation with a physician, as it may be necessary to reduce the maintenance dose or prolong the dosing interval.

The medicinal product should not be used for longer than 4–5 days without consulting a physician.

In acute conditions, consult a physician if symptoms persist or worsen despite treatment.

The solution may be diluted with water, tea, fruit juice, or milk. It may be taken independently of food intake.

The product should not be used for longer than 4–5 days without consulting a physician.

The secretolytic effect of the product is supported by adequate fluid intake.

Children

The product can be used in children. In children under 2 years of age, the product should be used only on medical advice.

Overdose

There are currently no reports of cases of overdose. Symptoms described in isolated reports of overdose and/or medication errors correspond to the known adverse effects observed with recommended doses of the product and require symptomatic treatment.

Adverse reactions.

The following frequency categories were used to assess adverse reactions:

Immune system side effects:

Rare – hypersensitivity reactions;

Frequency unknown – anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.

Skin and subcutaneous tissue side effects:

Rare – rash, urticaria;

Frequency unknown – serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

Nervous system side effects:

Common – dysgeusia (altered taste sensation).

Gastrointestinal side effects:

Common – nausea, oral numbness;

Uncommon – vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth;

Rare – throat dryness;

Very rare – hypersalivation.

Respiratory, thoracic and mediastinal side effects:

Common – pharyngeal numbness;

Very rare – dyspnea and bronchospasm;

Frequency unknown – dyspnea (as a symptom of hypersensitivity reaction).

General disorders:

Uncommon – fever, mucosal reactions.

Shelf life. 2 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

50 ml or 100 ml of solution in a bottle closed with a dropper stopper under a screw cap and supplied with a measuring cup in a carton.

Prescription status.

Over-the-counter.

Manufacturer.

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.