Ambroxol-lubnipharm

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMBROXOL-LUBNYFARM (AMBROXOL-LUBNYPHARM)

Composition:

Active substance: ambroxol hydrochloride;

1 ml of infusion solution contains 7.5 mg of ambroxol hydrochloride;

Excipients: citric acid monohydrate; disodium phosphate dihydrate; sodium chloride; water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear, colorless solution, practically free from particles.

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

Pharmacological properties.

Pharmacodynamics.

Ambroxol hydrochloride, a substituted benzylamine, is a metabolite of bromhexine. It differs from bromhexine by the absence of a methyl group and the presence of a hydroxyl group in the para-trans-position of the cyclohexyl ring.

Ambroxol exerts a secretolytic and secretomotor effect in the bronchial tract.

In preclinical studies, it increased the serous component fraction of bronchial secretion. Ambroxol facilitates mucus clearance by reducing viscosity and activating the ciliated epithelium.

Ambroxol activates the surfactant system through a direct effect on type II pneumocytes in the alveoli and Clara cells in the region of the small airways. It enhances the formation and release of surfactant material in the alveoli and bronchial tree of both fetuses and adults. These effects have been demonstrated in various biological species, in cell cultures, and in vivo.

Furthermore, antioxidant effects of ambroxol have been demonstrated in various preclinical studies.

Pharmacokinetics.

After intravenous administration, the bioavailability of the drug is by definition 100%. Following intravenous administration, the pharmacokinetics of ambroxol within the therapeutic dose range of 15–90 mg are linear and dose-proportional; even after intravenous administration of 1.0 g, no significant deviations from linearity are observed.

Distribution

Approximately 85% (80–90%) of the drug is bound to plasma proteins. In lung tissue, ambroxol reaches higher concentrations than in plasma after parenteral administration. Ambroxol can penetrate into cerebrospinal fluid, cross the placental barrier, and is excreted into breast milk.

Biotransformation

Formation of metabolites capable of entering the kidneys (e.g., dibromanthranilic acid, glucuronide) occurs in the liver.

Elimination

Almost 90% of the drug is excreted by the kidneys in the form of metabolites produced in the liver. Less than 10% of ambroxol is excreted unchanged by the kidneys. Due to the high degree of protein binding, large volume of distribution, and slow redistribution of the drug from tissues into blood, significant elimination of ambroxol by dialysis or forced diuresis is unlikely.

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

Patients with hepatic or renal impairment

In patients with severe hepatic dysfunction, the clearance of ambroxol is reduced by 20–40%. In patients with severe renal impairment, accumulation of ambroxol metabolites should be considered.

Children with renal impairment

In neonates with renal impairment who received repeated intravenous doses of ambroxol, the elimination half-life was approximately doubled, indicating reduced clearance.

Clinical characteristics.

Indications.

To enhance pulmonary surfactant production in premature infants and newborns with respiratory distress syndrome.

Contraindications.

Hypersensitivity to ambroxol hydrochloride or other components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Clinically significant interactions of ambroxol with other medicinal products have not been established to date.

Concomitant use of the medicinal product Ambroxol-Lubnifarm and cough-suppressant agents may result in excessive mucus accumulation due to suppression of the cough reflex. Such combination is possible only after careful physician assessment of the benefit-risk ratio of the treatment.

Laboratory tests

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

Special precautions for use

There have been reports of severe skin reactions associated with the use of ambroxol hydrochloride, including erythema multiforme, Stevens-Johnson syndrome / toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. If symptoms of progressive skin rash (sometimes with blistering or mucosal involvement) occur, treatment with ambroxol hydrochloride should be discontinued immediately and medical advice should be sought.

If intravenous administration is performed too rapidly, headache, increased fatigue, exhaustion, and a sensation of heaviness in the legs may very rarely occur.

Since ambroxol may enhance mucus secretion, Ambroxol-Lubnypharm, infusion 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).

Ambroxol-Lubnypharm, infusion solution, contains less than 1 mmol (23 mg) of sodium per ampoule, i.e. essentially "sodium-free".

Ambroxol-Lubnypharm, infusion solution, should be used with caution in patients with renal impairment or severe hepatic disease. As with any active substance metabolized in the liver and subsequently excreted by the kidneys, accumulation of metabolites formed in the liver may be expected in patients with severe renal insufficiency.

Use during pregnancy or breastfeeding

Not applicable, as the medicinal product is administered to premature infants and newborns.

Effect on ability to drive and use machines

Data not available due to lack of indication.

Method of Administration and Dosage

For intravenous infusion.

Dosage

30 mg per kg of body weight per day, divided into 4 single doses.

Dosing in Renal and/or Hepatic Impairment

In severe renal impairment or severe hepatic impairment, the maintenance dose should be appropriately reduced or the dosing interval extended.

The solution should be administered using an infusion pump as a short infusion lasting at least 5 minutes.

Duration of treatment — 5 days.

The contents of 1–6 ampoules should be diluted in 250–500 ml of physiological saline or Ringer's solution. The solution diluted with physiological saline or Ringer's solution is physically and chemically stable for 24 hours at 15–25 °C. From a microbiological standpoint, if opening of ampoules and dilution involve a risk of microbial contamination, the solution should be used immediately after preparation. If not, the responsibility for storage conditions and duration lies with the user. If neither of these diluents is available, 5% glucose solution may be used as an alternative. When using 5% glucose solution, the ampoule contents should be diluted immediately before use. If the solution is not used immediately after preparation, it must be discarded.

Children

Administered to preterm infants and newborns as indicated.

Overdose

There are currently no reports of specific overdose symptoms. Symptoms observed in cases of accidental overdose or medical error are similar to known adverse reactions occurring with recommended doses and may require symptomatic treatment.

Side effects.

The following classification was used to assess the frequency of adverse events:

Immune system side effects:

Rare: hypersensitivity reactions;

Not known: anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.

Skin and subcutaneous tissue side effects:

Uncommon: erythema;

Rare: rash, urticaria;

Not known: serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

Gastrointestinal side effects:

Uncommon: dry mouth, constipation, hypersalivation, dry throat;

Not known: nausea, vomiting, diarrhea, dyspepsia, abdominal pain.

Respiratory, thoracic and mediastinal side effects:

Uncommon: rhinorrhea, dyspnea (as a symptom of hypersensitivity reaction).

Renal and urinary system side effects:

Uncommon: urinary disorders.

General disorders and administration site conditions:

Uncommon: increased body temperature and chills, mucosal reactions.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicinal product registration is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report all suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine.

Shelf life. 3 years.

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

Storage conditions.

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

Keep out of the reach of children.

Incompatibility.

Ambroxol-Lubnifarm, infusion solution, should not be mixed with other solutions except physiological saline and Ringer's solution.

Packaging.

2 ml in an ampoule; 5 ampoules in a blister pack made of film, 1 or 2 blisters per cardboard box.

2 ml in an ampoule; 10 ampoules in a blister pack made of film, 1 blister per cardboard box.

2 ml in an ampoule; 5 or 10 ampoules per cardboard box with cardboard dividers.

Prescription category.

Prescription only.

Manufacturer.

JSC "Lubnifarm".

Manufacturer's address and location of its business activity.

16, Barvinkova Street, Lubny, Poltava region, 37500, Ukraine.