Ambroxol-teva

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

Composition:

Active substance: ambroxol hydrochloride;

One prolonged-release capsule contains 75 mg of ambroxol hydrochloride;

Excipients: microcrystalline cellulose, sodium carboxymethylcellulose – microcrystalline cellulose, hypromellose, triethyl citrate, colloidal hydrated silicon dioxide, methacrylic acid copolymer dispersion, gelatin, iron oxide yellow (E 172), iron oxide black (E 172), iron oxide red (E 172), titanium dioxide (E 171).

Pharmaceutical form. Prolonged-release hard capsules.

Main physico-chemical properties: capsule shell: colorless transparent; cap: opaque brown. Contents of capsules: granules from white to light yellow.

Pharmacotherapeutic group. Medicinal products used in cough and common cold. Mucolytic agents. ATC code R05C B06.

Pharmacological properties.

Pharmacodynamics.

It has been demonstrated that ambroxol hydrochloride increases secretion of the respiratory tract glands. Ambroxol enhances pulmonary surfactant secretion and stimulates ciliary activity, thereby facilitating mucus clearance and expectoration (mucociliary clearance). Improvement of mucociliary clearance has been confirmed during clinical and pharmacological studies. Activation of fluid secretion and increased mucociliary clearance facilitate mucus elimination and reduce coughing.

The local anesthetic effect of ambroxol hydrochloride may be explained by its ability to block sodium channels. In vitro studies have shown that ambroxol hydrochloride blocks neuronal sodium channels; binding was reversible and concentration-dependent.

In vitro studies have demonstrated that ambroxol hydrochloride significantly reduces cytokine release from blood and tissue-bound mononuclear and polymorphonuclear cells.

Significant reduction in throat pain and redness has been reported in patients with pharyngitis treated with ambroxol.

The medicinal product rapidly relieves pain and pain-related discomfort in the nasal cavity, ear region, and trachea during inhalation when treating upper respiratory tract disorders.

Use of ambroxol increases the concentration of antibiotics—amoxicillin, cefuroxime, erythromycin, and doxycycline—in sputum and bronchopulmonary secretions.

Pharmacokinetics.

Absorption. The drug exhibits slow absorption. After oral administration, maximum plasma concentration (Tmax) is reached approximately after 9 hours.

Distribution. Plasma protein binding is about 85%. The prolonged-release formulation of Ambroxol-Teva is characterized by sustained release of the active substance.

Ambroxol penetrates into cerebrospinal fluid, crosses the placental barrier, and is excreted in breast milk.

Metabolism. Metabolite formation (dibromoanthranilic acid, glucuronides) occurs in the liver.

Elimination. Approximately 90% of the drug is excreted by the kidneys in the form of metabolites. Less than 10% of ambroxol is excreted unchanged by the kidneys.

Due to the high degree of plasma protein binding, large volume of distribution, and slow redistribution of the drug from tissues into blood, significant elimination of ambroxol during dialysis or forced diuresis is unlikely. The elimination half-life from plasma is approximately 10 hours.

Hepatic and renal impairment

In patients with severe liver disease, ambroxol clearance is reduced by 20–40%. In patients with severe renal impairment, prolonged elimination half-life of ambroxol metabolites is observed.

Clinical characteristics.

Indications.

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

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the medicinal product Ambroxol-Teva, prolonged-release capsules, and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination is possible only after careful evaluation by a physician of the benefit-risk ratio of the treatment.

Administration of the medicinal product Ambroxol-Teva, prolonged-release capsules 75 mg, in combination with antibiotics (with amoxicillin, cefuroxime, erythromycin, doxycycline) may improve antibiotic delivery to lung tissues. This interaction with doxycycline is widely used for therapeutic purposes.

There are no reports of adverse interactions with other medicinal products.

Special precautions for use.

There have been only a few reports of severe skin reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) associated with the use of expectorant agents such as ambroxol hydrochloride. In most cases, these could be explained by the severity of the underlying disease in patients and/or concomitant use of other medicinal products. There have also been reports of other serious skin reactions such as erythema multiforme and acute generalized exanthematous pustulosis associated with the use of ambroxol. If skin rashes develop or worsen (sometimes associated with blisters or mucosal lesions), ambroxol should be discontinued immediately and medical advice should be sought.

At the initial stage of Stevens-Johnson syndrome or Lyell's syndrome, patients may present with non-specific symptoms resembling the onset of influenza, such as fever, malaise, rhinitis, cough, and sore throat. Symptomatic treatment with cough and cold remedies may be mistakenly used when such non-specific, flu-like symptoms are present.

Since ambroxol may enhance mucus secretion, Ambroxol-Teva, prolonged-release capsules, 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).

In patients with severe renal impairment, accumulation of hepatic metabolites of ambroxol may occur. Patients with renal dysfunction 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. Preclinical studies have not revealed any direct or indirect adverse effects on pregnancy, embryonal/fetal development, uterine contractility, or labor, or postnatal development. Extensive clinical experience with the use of the drug after the 28th week of pregnancy has not shown any harmful effects on the fetus. However, usual precautions for the use of medicinal products during pregnancy should be observed. Particularly, the use of this drug is not recommended during the first trimester of pregnancy.

Breastfeeding

According to preclinical data, ambroxol hydrochloride is excreted into breast milk. Ambroxol is not recommended during breastfeeding.

Fertility

There are no clinical data indicating a direct or indirect effect on fertility.

Ability to influence the reaction rate while driving or operating machinery.

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

Dosage and Administration

Ambroxol-Teva, 75 mg prolonged-release capsules, should be taken orally. The capsules should be swallowed whole with a sufficient amount of warm liquid (water, tea, fruit juice), after food.

The mucolytic effect of ambroxol is enhanced by increased fluid intake.

Adults: 1 capsule once daily. The duration of treatment depends on the nature of the disease course. Generally, there are no limitations regarding the duration of use; however, prolonged therapy should be conducted under medical supervision. It is not recommended to take Ambroxol-Teva 75 mg prolonged-release capsules without a doctor's prescription for longer than 4–5 days.

If symptoms persist or worsen despite treatment, a physician should be consulted.

In cases of renal function impairment and severe liver disease, the drug should be administered only under medical supervision. In such cases, a dose reduction and prolonged interval between doses are recommended.

Children: Ambroxol-Teva prolonged-release capsules are not used in pediatric practice. For children, Ambroxol-Teva syrup or drops are recommended.

Overdose

Currently, there are no reports of specific overdose symptoms in humans. Symptoms described in isolated cases of overdose and/or accidental ingestion correspond to the known adverse effects of ambroxol at recommended doses and require symptomatic treatment.

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); not known (cannot be estimated from the available data).

Immune system disorders:

rare – hypersensitivity reactions;

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

Skin and subcutaneous tissue disorders:

rare – skin rash, urticaria;

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

Gastrointestinal disorders:

common – nausea;

uncommon – vomiting, dyspepsia, abdominal pain, diarrhea;

very rare – hypersalivation.

Respiratory system disorders:

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

General disorders:

uncommon – fever, mucosal reactions.

Shelf life.

5 years.

Storage conditions. Store at temperatures not exceeding 25 °C in a place inaccessible to children.

Packaging.

10 capsules per blister, 1 blister per carton.

Availability category. Over-the-counter.

Manufacturers.

Merckle GmbH.

Acino Estonia OU.

Manufacturers' addresses and locations of their business operations.

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

Jaama 55b, Põlva, Põlva County, 63308, Estonia.