Ambroxol hydrochloride

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROXSOL HYDROCHLORIDE (AMBROXOL HYDROCHLORIDE)

Composition:

Active substance: ambroxol hydrochloride;

One tablet contains 30 mg of ambroxol hydrochloride;

Excipients: lactose monohydrate, copovidone, colloidal anhydrous silicon dioxide, crospovidone, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or white with a yellowish tint, round-shaped tablets with a flat surface and beveled edges.

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

Pharmacological Properties.

Pharmacodynamics.

Ambroxol increases secretion of the respiratory tract glands, reduces the viscosity of bronchial mucus, stimulates ciliary activity of the respiratory tract, and enhances surfactant production in the lungs. These effects lead to improved mucus clearance (mucociliary clearance). Activation of fluid secretion and increased mucociliary clearance facilitate the removal of mucus and reduce coughing.

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

Pharmacokinetics.

Absorption of the drug is rapid and sufficiently complete after oral administration. The effect of the drug begins within 30 minutes after oral administration and lasts for 6–12 hours, depending on the individual dose.

Maximum plasma concentrations are achieved within 1–3 hours. Absolute bioavailability of ambroxol is reduced by one-third after oral administration due to first-pass metabolism. The extent of ambroxol binding to plasma proteins is 80–90%.

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

Distribution of ambroxol from blood to tissues is rapid, with high concentrations of the active substance found in the lungs. The drug penetrates the blood-brain and placental barriers and is excreted into breast milk.

Ambroxol is metabolized in the liver via conjugation. The resulting metabolites are excreted in urine (e.g., dibromanthranilic acid, glucuronides). Approximately 90% is eliminated by the kidneys in the form of water-soluble metabolites, and less than 10% is excreted unchanged. Elimination half-life is prolonged in cases of severe chronic renal insufficiency.

Ambroxol clearance is reduced by 20–40% in cases of severe liver disease. Accumulation of ambroxol metabolites may be expected in patients with severe hepatic impairment.

Dialysis or forced diuresis are not expected to enhance ambroxol elimination from blood, considering its high degree of protein binding, large volume of distribution, and slow redistribution from tissues into blood.

Clinical characteristics.

Indications.

Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and weakened expectoration.

Contraindications.

• Hypersensitivity (allergy) to ambroxol or to other components of the drug;
• Rare hereditary disorders of carbohydrate intolerance: congenital galactosemia, glucose-galactose malabsorption syndrome, lactase deficiency (due to the presence of lactose in the drug).

Interaction with other medicinal products and other types of interactions.

Concomitant use of ambroxol with antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) promotes increased antibiotic concentrations in lung tissue.

Concomitant use of ambroxol hydrochloride with antitussive agents may lead to impaired expectoration due to reduced coughing. Therefore, such a combination is possible only after careful evaluation by a physician of the expected benefits versus the potential risks of use.

Special precautions for use

When using mucolytic agents, including ambroxol hydrochloride, isolated cases of severe skin reactions have been reported, such as erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), and acute generalized exanthematous pustulosis. These were mostly attributable to the severity of the underlying disease and/or concomitant therapy. Additionally, during the initial stages of Stevens-Johnson syndrome or Lyell's syndrome, patients may experience influenza-like nonspecific prodromal symptoms such as fever, body aches, rhinitis, cough, and sore throat. As a result of misinterpretation of these symptoms, patients might receive medications for symptomatic treatment of cough and colds. Therefore, if progressive skin lesions (sometimes associated with blister formation or mucosal involvement) occur, the drug should be discontinued immediately and medical help should be sought.

The medication should be used with caution in patients with gastric or duodenal ulcer disease.

In cases of renal impairment or severe liver disease, the medication should be used only after consultation with a physician; it may be necessary to prolong the dosing intervals or reduce the dose. Ambroxol hydrochloride is metabolized in the liver and excreted by the kidneys; therefore, in severe renal insufficiency, accumulation of ambroxol and/or its metabolites in the body may occur.

During treatment, it is necessary to consume sufficient fluids (juices, tea, water) to enhance the mucolytic effect of the medication.

Mucolytic agents (including ambroxol) should be used with caution in conditions involving increased mucus secretion or impaired bronchial motor function (e.g., in rare genetically determined disorders such as primary ciliary dyskinesia) due to the risk of accumulation of large amounts of mucus.

The medication contains lactose; therefore, it should not be administered to patients with rare hereditary disorders of carbohydrate intolerance (congenital galactosemia, glucose-galactose malabsorption syndrome, lactase deficiency). If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medication.

Use during pregnancy or breastfeeding

Pregnancy

Ambroxol hydrochloride crosses the placental barrier. Clinical studies on the use of ambroxol hydrochloride have not shown any harmful effects on the fetus after the 28th week of pregnancy. However, usual precautions regarding medication use during pregnancy should be observed. The medication is not recommended during the first trimester of pregnancy. During the second and third trimesters, the medication may be used only after careful assessment of the benefit-risk ratio for the mother and potential risk to the fetus.

Breastfeeding

Ambrox combustible hydrochloride passes into breast milk; therefore, the medication is not recommended during breastfeeding.

Fertility

Preclinical studies have not shown any direct or indirect adverse effects on fertility.

Ability to affect reaction speed when driving vehicles or operating machinery

There are no data regarding the effect on reaction speed when driving vehicles or operating machinery.

Method of Administration and Dosage.

If not otherwise prescribed, it is recommended:

For adults and children aged 12 years and older: during the first 2–3 days, take 30 mg (1 tablet) 3 times daily (equivalent to 90 mg of ambroxol hydrochloride/day), then reduce to 30 mg (1 tablet) 2 times daily (equivalent to 60 mg of ambroxol hydrochloride/day).

The therapeutic effect may be enhanced by administering the drug at a dose of 60 mg (2 tablets) 2 times daily, equivalent to 120 mg of ambroxol hydrochloride per day.

The tablets should be taken during or after meals. Do not chew the tablets; swallow them with sufficient amount of liquid (e.g., water, tea, juice).

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

Children.

Do not administer to children under 12 years of age.

Overdose.

Symptoms. Ambroxol was well tolerated following parenteral administration at doses up to 15 mg/kg/day and oral administration up to 25 mg/kg/day. After ambroxol overdose, severe signs of intoxication have not been observed. Cases of transient restlessness and diarrhea have been reported.

Significant overdose may lead to hypersalivation, nausea/vomiting, and decreased arterial blood pressure.

Treatment. Emergency measures such as induction of emesis and gastric lavage are generally not indicated and should only be considered in cases of acute intoxication. Symptomatic treatment is recommended.

Side effects.

Gastrointestinal tract: dyspepsia, heartburn, nausea, vomiting, abdominal pain, diarrhea/constipation, hypersalivation, dry mouth, hypoaesthesia of the oral and/or pharyngeal mucosa.

Respiratory system, thoracic organs and mediastinum: rhinorrhea, dryness of the upper respiratory tract mucosa, dyspnea (as a symptom of hypersensitivity reaction).

Urinary system: dysuria.

Nervous system: dysgeusia (disturbance of taste sensation).

Immune system, skin and subcutaneous tissues: hypersensitivity reactions, including pruritus, skin rash, urticaria, angioneurotic edema, anaphylactic reactions (including anaphylactic shock), drug fever, chills, and other allergic reactions. Severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), and acute generalized exanthematous pustulosis may occur very rarely.

Other: mucous membrane reactions.

Shelf life. 4 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of the reach of children.

Packaging.

10 tablets per blister, 2 blisters per carton.

Availability category. Over-the-counter.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchagov Chemical and Pharmaceutical Plant".

Limited Liability Company "Agrofarm".

Manufacturer's address and place of business.

Ukraine, 03134, Kyiv, Miru Street, 17.

Ukraine, 08200, Irpin, Kyiv region, Centralna Street, 113-A.