Ambrotard 75

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROTARD 75 (AMBROTARD 75)

Composition:

Active substance: ambroxol hydrochloride;

1 capsule contains ambroxol hydrochloride, pellets with prolonged release, calculated as ambroxol hydrochloride – 75 mg;

Excipients: in the pellet composition: spherical sugar, shellac, povidone, talc;

hard gelatin capsule size № 2: patent blue V (E 131); gelatin.

Pharmaceutical form. Prolonged-release capsules.

Main physicochemical properties: hard capsules with a transparent greenish-blue cap and a transparent colorless body, containing creamy-white pellets.

Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytic agents. Ambroxol. ATC Code R05CB06.

Pharmacological properties.

Pharmacodynamics.

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

Administration of ambroxol increases concentrations of antibiotics amoxicillin, cefuroxime, erythromycin, and doxycycline in sputum and bronchopulmonary secretions.

Pharmacokinetics.

Maximum plasma concentrations are reached approximately 6.5 hours after administration of the prolonged-release dosage form. The relative bioavailability of prolonged-release capsules is 95%. The extent of ambroxol binding to plasma proteins is 80–90%.

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

Ambroxol is metabolized in the liver via conjugation. The metabolites formed are excreted in urine (e.g., dibromanthranilic acid, glucuronides). Approximately 90% is excreted by the kidneys as water-soluble metabolites, and less than 10% is excreted unchanged. The elimination half-life from plasma is approximately 10 hours.

The elimination half-life is prolonged in cases of severe chronic renal impairment.

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

Since the therapeutic range of ambroxol hydrochloride is sufficiently wide, dosage adjustment is not required.

Food intake does not affect the bioavailability of ambroxol hydrochloride.

Dialysis or forced diuresis are not expected to enhance the elimination of ambroxol from blood, considering the 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 disorders of bronchial secretion and impaired mucus clearance.

Contraindications.

Hypersensitivity (allergy) to ambroxol or to other components of the drug.

Interaction with other medicinal products and other forms of interaction.

The concomitant use of ambroxol with antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) enhances the concentration of antibiotics in lung tissue.

The concomitant use of ambroxol hydrochloride with antitussive agents may lead to suppression of mucus expectoration and excessive accumulation of mucus due to reduced coughing. Therefore, such a combination is possible only after careful assessment by a physician of the benefit-risk ratio.

Special precautions for use

When using mucolytic agents, including hydrochloride ambroxol, there have been isolated reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), and acute generalized exanthematous pustulosis. In most cases, these reactions could be explained by the severity of the underlying disease and/or concomitant therapy. Furthermore, during the initial stages of Stevens-Johnson syndrome or Lyell’s syndrome, patients may present with influenza-like non-specific prodromal symptoms such as fever, body aches, rhinitis, cough, and sore throat. As a result, these symptoms may be misinterpreted, leading patients to receive medications for symptomatic treatment of cough and cold. Therefore, if progressive skin reactions (sometimes associated with blistering or mucosal lesions) occur during treatment with Ambrotard 75, the drug should be discontinued immediately and medical help should be sought.

The medication should be used with caution in patients with peptic ulcer disease of the stomach and/or duodenum.

In cases of renal impairment or severe liver disease, the medication should only be administered after consultation with a physician. Ambroxol hydrochloride is metabolized in the liver and excreted by the kidneys. Therefore, in cases of severe chronic renal impairment, accumulation of ambroxol and/or its metabolites in the liver may occur.

During treatment, adequate fluid intake (juices, tea, water) is recommended to enhance the mucolytic effect of the drug.

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

"Gelatin capsules" occasionally found in feces have already released the active ingredient during passage through the gastrointestinal tract and thus do not indicate ineffective drug absorption.

Use during pregnancy or breastfeeding

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

Breastfeeding

Ambroxol hydrochloride passes into breast milk; therefore, the drug is not recommended during breastfeeding.

Fertility

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

Ability to influence reaction speed when driving or operating machinery

There are no data regarding the effect of this drug on the ability to drive or operate machinery.

Method of Administration and Dosage.

For adults: take orally 1 capsule (75 mg) once daily, with sufficient fluid (e.g., water, tea, or fruit juice). The capsules should be swallowed whole, without chewing. Ambrotard 75 may be taken regardless of food intake.

In acute conditions, consult a physician if symptoms do not resolve and/or worsen despite treatment. The medication should not be used for longer than 4–5 days without consulting a physician.

Children.

This medicinal form, i.e. prolonged-release capsules Ambrotard 75, should not be used in children.

Overdose.

Symptoms. Ambroxol was well tolerated after parenteral administration at doses up to 15 mg/kg/day and after oral administration up to 25 mg/kg/day. Severe signs of intoxication have not been observed following ambroxol overdose. 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 vomiting and gastric lavage are generally not indicated and should only be applied 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 mucous membrane of the upper respiratory tract, dyspnea (as a symptom of hypersensitivity reaction).

Urinary system: dysuria.

Nervous system: dysgeusia (taste disturbance).

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.

Others: mucosal reactions.

Shelf life. 2 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 reach and sight of children.

Packaging. 10 capsules in a blister, 1 blister per carton.

Supply category. Over-the-counter (without prescription).

Manufacturer.

Public joint-stock company "Scientific and Production Center "Borshchagov Chemical and Pharmaceutical Plant".

Manufacturer's location and address of business activity.

17 Myru Street, Kyiv, 03134, Ukraine.