Ambroxol-teva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ambroxol-Teva (Ambroxol-Teva)

Composition:

Active substance: ambroxol hydrochloride;

1 ml of solution contains ambroxol hydrochloride 7.5 mg;

Excipients: potassium sorbate (E 202), hydrochloric acid diluted (25%), purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, colorless, odorless solution.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. ATC code R05C B06.

Pharmacological properties.

Pharmacodynamics.

Ambroxol exerts a broncho-secretolytic and secretomotor (expectorant) effect. Ambroxol-Teva normalizes impaired bronchopulmonary secretion, improves rheological properties of sputum, reduces its viscosity, and facilitates the expectoration of sputum from the bronchi. The effect begins within 30 minutes and lasts for 6–12 hours. It increases pulmonary surfactant production and enhances mucociliary clearance.

The local anesthetic effect of ambroxol hydrochloride, which may be explained by its ability to block sodium channels, has been observed in a rabbit eye model. In vitro studies have shown that ambroxol hydrochloride blocks neuronal sodium channels; this binding was reversible and concentration-dependent.

Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. In vitro studies have revealed that ambroxol hydrochloride significantly reduces cytokine release from blood and tissue binding of mononuclear and polymorphonuclear cells.

In clinical trials involving patients with pharyngitis, significant reduction in throat pain and redness was demonstrated upon administration of the drug.

These pharmacological properties result in rapid relief of pain and associated discomfort in the nasal cavity, ear area, and trachea upon inhalation, consistent with supplementary symptom observation data from clinical efficacy studies of ambroxol in treating upper respiratory tract disorders.

After administration of ambroxol hydrochloride, increased concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin) are observed in bronchopulmonary secretions and sputum.

Pharmacokinetics.

Absorption. Ambroxol is almost completely absorbed after oral administration. Maximum concentration (Tmax) is reached within 1–3 hours after oral intake. Absolute bioavailability of ambroxol is reduced by one-third after oral administration due to first-pass metabolism.

Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and highly 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, approximately 90% of the drug is protein-bound within the therapeutic range.

Metabolism and elimination. Approximately 30% of the dose is eliminated following presystemic metabolism after oral administration. Ambroxol hydrochloride is metabolized primarily in the liver via 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 elimination half-life from plasma is approximately 10 hours. Total clearance is about 660 mL/min, with renal clearance accounting for approximately 83% of total clearance.

Pharmacokinetics in special patient populations. In patients with severe hepatic impairment, ambroxol clearance is reduced by 20–40%. In patients with severe renal insufficiency, accumulation of ambroxol metabolites should be expected.

Clinical characteristics.

Indications.

Secretolytic therapy in acute and chronic broncho-pulmonary diseases associated with impaired bronchial secretion and impaired mucus transport.

Contraindications.

Hypersensitivity to ambroxol and/or to other components of the medicinal product.

Interaction with other medicinal products and other types of interactions.

Concomitant use of ambroxol and antitussive agents may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should be used only after careful evaluation by a physician of the expected benefit versus possible risk of use.

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

Special precautions for use

Severe skin reactions (such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), and acute generalized exanthematous pustulosis) have been reported in association with ambroxol use. If skin rashes develop or worsen (sometimes associated with blisters or mucosal lesions), ambroxol should be discontinued immediately and medical advice should be sought.

Ambroxol Teva solution 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 mucus accumulation.

In patients with severe renal insufficiency, 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. Patients with impaired renal function and severe hepatic disorders should use ambroxol only after consultation with a physician.

Use during pregnancy or breastfeeding

Pregnancy

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

Clinical studies have shown no adverse effects on the fetus or course of pregnancy when the drug was used after the 28th week of gestation. Nevertheless, usual precautions for medication use during pregnancy should be observed. In particular, use during the first trimester of pregnancy is not recommended.

Breastfeeding

Ambroxol hydrochloride is excreted in breast milk. Although adverse effects on infants are not expected, ambroxol is not recommended during breastfeeding.

Fertility

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

Ability to influence reaction speed while driving or operating machinery

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

Dosage and Administration

Ambroxol-Teva solution is for oral use and should be taken after meals. Dose the medication using the measuring cup provided. Drops should be taken after eating, diluted in liquid (e.g., water, tea, or juice).

The mucolytic effect of ambroxol is enhanced by drinking plenty of fluids.

Children aged 12 years and adults: For the first 2–3 days – 4 mL three times daily (equivalent to 90 mg of ambroxol per day); thereafter – 4 mL twice daily (equivalent to 60 mg of ambroxol per day) or 2 mL three times daily (equivalent to 45 mg of ambroxol per day).

Children aged 6 to 12 years: 2 mL two to three times daily (equivalent to 30–45 mg of ambroxol per day).

Children aged 2 to 5 years: 1 mL three times daily (equivalent to 22.5 mg of ambroxol per day).

Children under 2 years of age: 1 mL twice daily (equivalent to 15 mg of ambroxol per day).

The duration of treatment depends on the course of the disease.

Ambroxol-Teva solution should not be used for longer than 4–5 days without consulting a physician.

In cases of renal impairment or severe liver disease, the medication should be taken only under medical supervision. In such cases, it is recommended to reduce the dose and increase the interval between doses.

In acute conditions, consult a physician if symptoms persist or worsen despite treatment with Ambroxol-Teva.

Children

This medicinal product can be used in children. In children under 2 years of age, the product should be used only as directed by a physician.

Overdose

There have been no reports of specific symptoms of overdose in humans. Symptoms reported in isolated cases of overdose and/or accidental ingestion correspond to the known adverse effects of ambroxol at recommended doses and require symptomatic treatment. The most commonly observed symptoms were transient restlessness and diarrhea.

According to preclinical studies, significant overdose may lead to increased salivation, nausea, vomiting, and arterial hypotension.

Adverse Reactions

Adverse reactions are categorized by frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Immune system side effects:

Rare – hypersensitivity reactions;

Frequency not known – anaphylactic reactions (including anaphylactic shock, angioneurotic edema, pruritus).

Gastrointestinal side effects:

Common – nausea, decreased oral sensation;

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

Rare – dry throat;

Very rare – hypersalivation.

Nervous system side effects:

Common – dysgeusia (altered taste sensation).

Respiratory system side effects:

Common – decreased sensation in the pharynx;

Frequency not known – dyspnea (as a symptom of hypersensitivity reaction).

Skin and subcutaneous tissue side effects:

Rare – rash, urticaria;

Frequency not known – severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

General disorders:

Uncommon – fever, mucosal reactions.

Shelf life. 5 years.

Storage conditions. The medicinal product does not require special storage conditions. Keep out of reach of children.

Packaging.

40 ml or 100 ml of solution in a bottle; 1 bottle with dropper cap and dosing cup in a carton.

Prescription status. Over-the-counter.

Manufacturer. Merckle GmbH.

Manufacturer's address and location of operations.

Ludwig-Merckle-Strasse 3, 89143 Blaubeuren, Germany.