Asibrox

INSTRUCTIONS for medical use of the medicinal product ASIBROX (ASIBROX)

Composition:

Active substance: acetylcysteine;

One ampoule (3 ml) contains 300 mg of acetylcysteine;

Excipients: disodium edetate, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection and inhalation.

Main physico-chemical properties: clear light pink solution.

Pharmacotherapeutic group.

Mucolytic agent. ATC code R05CB01.

Pharmacological Properties

Pharmacodynamics

The active substance of the medicinal product, acetylcysteine, acts as a mucolytic agent. The presence of sulfhydryl groups in the structure of acetylcysteine promotes the cleavage of disulfide bonds of acidic mucopolysaccharides in sputum, resulting in depolymerization of mucoproteins and reduction of mucus viscosity. It retains activity in the presence of purulent sputum.

Acetylcysteine exerts an antioxidant effect due to the presence of a nucleophilic thiol (SH) group that readily donates hydrogen, thereby neutralizing oxidative radicals.

The protective mechanism of acetylcysteine is based on the ability of its reactive sulfhydryl groups to bind free radicals.

Acetylcysteine easily penetrates into cells, where it is deacetylated to L-cysteine, which is used for the intracellular synthesis of glutathione.

Glutathione is a highly reactive tripeptide and a potent antioxidant and cytoprotective agent that captures endogenous and exogenous free radicals and toxins. Acetylcysteine prevents depletion and promotes increased synthesis of intracellular glutathione, which participates in cellular redox processes, thereby supporting the detoxification of harmful substances.

Pharmacokinetics

Following intravenous administration of 600 mg acetylcysteine, the maximum plasma concentration is 300 mmol/L, and the plasma half-life is 2 hours. Total clearance is 0.21 L/h/kg, and the volume of distribution at steady state is 0.34 L/kg. Acetylcysteine penetrates into the interstitial space and is predominantly distributed in the liver, kidneys, lungs, and bronchial secretions. Acetylcysteine and its metabolites are primarily excreted by the kidneys.

Clinical characteristics.

Indications.

Acute and chronic respiratory tract diseases associated with increased mucus production.

Contraindications.

• Hypersensitivity to the active substance and/or to excipients of the medicinal product;
• peptic ulcer of the stomach and duodenum in the stage of exacerbation;
• hemoptysis, pulmonary hemorrhage.

Interaction with other medicinal products and other forms of interaction.

Studies on the interaction of acetylcysteine with other medicinal products have been conducted only in adults.

Nitroglycerin.

Concomitant use with nitroglycerin may lead to pronounced arterial hypotension and dilation of the temporal artery. If simultaneous administration of these medicinal products is necessary, the patient must be under medical supervision for the development of hypotension, which may be severe. The patient should be warned about the possible occurrence of headache.

Antitussives.

Concomitant use with antitussive agents may enhance bronchial secretion retention due to suppression of the cough reflex. Acetylcysteine should not be used simultaneously with antitussive agents.

Bronchodilators, vasoconstrictors.

Acetylcysteine can be used concomitantly with common bronchodilators and vasoconstrictors.

Antibiotics.

Available data on the interaction between antibiotics and acetylcysteine come from in vitro studies and indicate reduced antibiotic activity after mixing with acetylcysteine. Therefore, mixing antibiotics with acetylcysteine solution is not recommended.

Effect on laboratory parameters.

Acetylcysteine use may alter the results of quantitative determination of salicylates by colorimetric methods and the results of urine ketone testing.

Special precautions for use.

Administration of acetylcysteine, particularly in aerosol form, may initially liquefy bronchial gland secretions and increase their volume. If the patient is unable to effectively expectorate mucus, postural drainage or bronchoaspiration should be performed to prevent mucus accumulation.

Intravenous administration.

Intravenous administration of the medicinal product must be carried out under strict medical supervision. Adverse reactions may occur more frequently with too rapid infusion or when high doses are administered. It is recommended to strictly follow the instructions provided in the section "Method of administration and dosage."

Use in patients with bronchial asthma.

Evidence suggests that patients with a history of atopy and asthma may have an increased risk of developing anaphylactoid reactions. Patients with bronchial asthma should be under medical supervision during treatment. If bronchospasm occurs, administration of the medicinal product must be discontinued immediately and appropriate treatment initiated.

Use in patients with a history of peptic ulcer.

The medicinal product should be administered with particular caution to patients with a history of peptic ulcer, especially when concomitantly taking other medicinal products that irritate the gastric mucosa.

Use in patients with histamine intolerance.

The medicinal product should be used cautiously in patients with histamine intolerance, and prolonged treatment should be avoided due to the potential effect of acetylcysteine on histamine metabolism and the possible occurrence of intolerance symptoms (e.g. headache, rhinitis, pruritus).

Use in children.

The same warnings and precautions indicated for adults apply to children and adolescents.

Risk of anaphylactoid reactions.

Anaphylactoid reactions/hypersensitivity reactions may occur during administration of acetylcysteine. Patients should be closely monitored for signs of anaphylactoid reactions during treatment.

The sulfurous odor observed upon opening the vial is a characteristic smell of the active substance acetylcysteine and does not in any way affect the possibility of using the medicinal product.

The solution of acetylcysteine in opened vials may rarely turn slightly purple when transferred to aerosol equipment; this does not affect its efficacy or tolerability.

The medicinal product contains 42.2 mg of sodium per vial and should therefore be used with caution in patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy.

Clinical data on the use of acetylcysteine in pregnant women are limited.

Animal studies do not indicate any direct or indirect harmful effects on reproductive function.

Before administering the medicinal product during pregnancy, the potential risks to the fetus should be weighed against the expected benefits to the mother.

Breastfeeding period.

There is no information available on the excretion of the drug and its metabolites in human milk.

A risk to the infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abandon treatment with the medicinal product, taking into account the benefits of breastfeeding for the infant and the benefits of therapy for the woman.

Fertility.

There are no data on the effect of acetylcysteine on human fertility. Animal studies do not indicate any harmful effect on human fertility when administered at recommended doses.

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

There are no data indicating that acetylcysteine affects the ability to drive or operate machinery.

Method of Administration and Dosage

Local administration.

Inhalation administration.

The medicinal product should be administered: to adults – at a dose of 300 mg (1 ampoule) 1–2 times daily as prescribed by a physician for 5–10 days; to children aged 6 years and older – up to 300 mg (1 ampoule) 1–2 times daily as prescribed by a physician for 5–10 days.

Endobronchial administration.

The medicinal product should be administered: to adults and children aged 6 years and older – at a dose of up to 300 mg (1 ampoule) 1–2 times daily.

Systemic administration.

Intramuscular administration.

The medicinal product should be administered deep intramuscularly to adults at a dose of 300 mg (1 ampoule) 1–2 times daily.

Intravenous administration.

The medicinal product should be administered slowly by intravenous infusion in 0.9% sodium chloride solution or 5% glucose solution to adults at a dose of 300 mg (1 ampoule) 1–2 times daily.

Children.

The medicinal product is administered locally to children aged 6 years and older.

The medicinal product should not be administered to children by intramuscular or intravenous routes.

Overdose.

Intravenous administration.

Symptoms.

Symptoms of overdose are similar to those of adverse reactions but of greater severity.

Treatment.

Treatment requires immediate discontinuation of the medicinal product and initiation of symptomatic therapy and resuscitation measures. There is no specific antidote. Dialysis is effective.

Local administration.

Symptoms.

Cases of overdose have not been reported. High doses of acetylcysteine may induce excessive bronchopulmonary secretion, leading to airway obstruction.

Treatment.

Bronchoaspiration should be performed.

Side effects.

During post-marketing use, the following adverse reactions have been reported; their frequency is unknown (cannot be estimated from the available data):

Inhalation administration.

Immune system disorders:

hypersensitivity reactions.

Respiratory, thoracic and mediastinal disorders:

bronchospasm, rhinorrhea, bronchial obstruction.

Gastrointestinal disorders:

stomatitis, vomiting, nausea.

Skin and subcutaneous tissue disorders:

urticaria, rash, pruritus.

Parenteral administration.

Immine system disorders:

hypersensitivity reactions, including anaphylactic shock, anaphylactic reactions, anaphylactoid reactions.

Cardiac disorders:

tachycardia.

Respiratory, thoracic and mediastinal disorders:

bronchospasm, dyspnea.

Gastrointestinal disorders:

nausea, vomiting, abdominal pain, diarrhea, dyspepsia, pyrosis.

Skin and subcutaneous tissue disorders:

angioneurotic edema, urticaria, erythema, rash, pruritus, exanthema.

General disorders and administration site conditions:

facial swelling, headache, tinnitus, hemorrhage, hyperthermia.

Investigations:

decreased blood pressure, anemia, prolonged prothrombin time.

Very rarely, serious skin reactions such as Stevens–Johnson syndrome and Lyell’s syndrome have been observed during acetylcysteine use. In most cases, there was suspicion that the above-mentioned mucocutaneous syndromes might have been caused by concomitant use of at least one other medicinal product. If mucocutaneous changes occur, medical advice must be sought and acetylcysteine should be discontinued immediately.

Decreased platelet aggregation with acetylcysteine has been confirmed by some studies. The clinical significance of these findings has not yet been established.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is highly important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging and in a place inaccessible to children.

Packaging.

3 ml in an ampoule; 5 ampoules in a blister pack; 1 or 2 blister packs in a cardboard box.

Incompatibilities.

Acetylcysteine solution must not come into contact with rubber or metal surfaces.

It is recommended to use glass or plastic equipment for inhalations. After use, the equipment should be rinsed with water.

Prescription status.

By prescription only.

Manufacturer.

Mefar Ilac San. A.S.

Manufacturer's address and location of operations.

Ramazanoglu Mah. Ensar Cad. No: 20, 34906 Kurtkoy – Pendik/Istanbul, Turkey.

Marketing authorization holder.

WORLD MEDICINE, LLC, Ukraine.