Ambroxol-teva

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

Composition:

Active substance: ambroxol hydrochloride;

5 ml of syrup contains ambroxol hydrochloride 15 mg;

Excipients: non-crystallizing sorbitol solution, propylene glycol, raspberry flavor, saccharin, benzoic acid, purified water.

Pharmaceutical form. Syrup.

Main physico-chemical properties: clear, colorless or yellowish solution with a raspberry aroma.

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

Pharmacological properties.

Pharmacodynamics.

Ambroxol hydrochloride increases the secretion of the respiratory tract glands. Ambroxol enhances pulmonary surfactant excretion by direct action on type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates ciliary activity. This leads to increased mucus secretion and clearance, improving mucociliary clearance.

Activation of fluid secretion and enhancement of mucociliary clearance facilitate mucus elimination and reduce coughing.

A local anesthetic effect of ambroxol hydrochloride has been reported, which may be explained by its ability to block sodium channels. In vitro studies have shown that ambroxol hydrochloride reversibly and concentration-dependently blocks neuronal sodium channels.

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

Significant reduction in throat pain and redness has been observed in patients with pharyngitis upon administration of the drug.

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

Pharmacokinetics.

Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and fairly complete, with linear 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 after 6.5 hours with sustained-release formulations.

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

Metabolism and elimination. Approximately 30% of the dose is eliminated following first-pass metabolism after oral administration. Ambroxol hydrochloride is metabolized mainly in the liver via glucuronidation and cleavage into dibromoaniline acid (approximately 10% of the dose). CYP3A4 has been shown to be responsible for the metabolism of ambroxol hydrochloride into dibromoaniline acid.

Approximately 6% of the dose is excreted unchanged, while about 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 groups. 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.

Food intake does not affect the bioavailability of ambroxol hydrochloride.

Clinical characteristics.

Indications.

Mucolytic therapy in acute and chronic broncho-pulmonary diseases associated with impaired bronchial secretion and weakened mucus clearance.

Contraindications.

Hypersensitivity to ambroxol and/or to any of the excipients of the medicinal product.

Rare hereditary conditions leading to incompatibility with the excipient of the medicinal product (see section "Special precautions").

Interaction with other medicinal products and other forms of interaction.

Concomitant use of ambroxol and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should only be used after careful assessment by a physician of the benefit-risk ratio.

Special precautions for use

Serious skin reactions (including 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 occur or progress (sometimes associated with blisters or mucosal lesions), ambroxol should be discontinued immediately and medical advice should be sought.

Ambroxol-Teva syrup 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.

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 hepatically formed ambroxol metabolites. Patients with impaired renal function or severe hepatic disorders should use ambroxol only after consultation with a physician.

Ambroxol-Teva syrup contains sorbitol. Each 5 ml of syrup contains 2.1 g of sorbitol (equivalent to 0.18 XE). The energy value of 1 g of sorbitol is 2.6 kcal. Sorbitol may have a mild laxative effect. Patients with rare hereditary fructose intolerance should not take this medicinal product.

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, parturition, or postnatal development.

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

Breastfeeding

Ambroxol hydrochloride passes into breast milk. Although adverse effects on the infant are not expected, ambroxol is not recommended during breastfeeding.

Fertility

Preclinical studies have not indicated any direct or indirect harmful effects on fertility.

Ability to affect reaction speed when driving or operating machinery

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

Dosage and Administration

Ambroxol-Teva syrup is taken orally after meals. After administration, it is recommended to drink one glass of water. The mucolytic effect of ambroxol is enhanced by increased fluid intake.

Adults and children aged 12 years and older: during the first 2–3 days – 10 mL three times daily (equivalent to 90 mg of ambroxol hydrochloride per day), thereafter – 10 mL twice daily (equivalent to 60 mg of ambroxol hydrochloride per day). If necessary, the therapeutic effect in adults and children aged 12 years and older may be enhanced by increasing the dose to 20 mL twice daily (equivalent to 120 mg of ambroxol hydrochloride per day).

For adults and children aged 12 years and older, it is advisable to use a medicinal formulation containing a higher concentration of ambroxol hydrochloride (e.g., Ambroxol-Teva solution, 37.5 mg/5 mL).

Children:

• aged under 2 years (excluding newborns and premature infants) – 2.5 mL twice daily (equivalent to 15 mg of ambroxol hydrochloride per day);
• aged 2 to 5 years – 2.5 mL three times daily (equivalent to 22.5 mg of ambroxol hydrochloride per day);
• aged 6 to 12 years – 5 mL two to three times daily (equivalent to 30–45 mg of ambroxol hydrochloride per day).

Duration of treatment depends on the nature and course of the disease.

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

Children.

This medicinal product can be used in children. Use in children under 2 years of age is permitted only under medical supervision.

Overdose.

There are currently 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 effects were transient restlessness and diarrhea.

According to preclinical studies, in cases of significant overdose, increased salivation, nausea, vomiting, and arterial hypotension may occur.

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).

From the immune system:

rare – hypersensitivity reactions;

frequency not known – anaphylactic reactions, including anaphylactic shock, angioedema, pruritus.

From the gastrointestinal system:

common – nausea, oral paresthesia;

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

rare – dry throat;

very rare – hypersalivation.

From the nervous system:

common – dysgeusia (taste disturbance).

From the respiratory system:

common – pharyngeal hypoesthesia;

frequency not known – dyspnea (as a hypersensitivity reaction).

From the skin and subcutaneous tissue:

rare – rash, urticaria;

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

General disorders:

uncommon – pyrexia, mucosal reactions.

Shelf life. 5 years.

After first opening of the bottle – 12 months.

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

Packaging.

100 ml of syrup in a bottle; 1 bottle with a measuring cup in a carton.

Prescription status. Over-the-counter.

Manufacturer. Merckle GmbH.

Manufacturer's address and place of business.

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