Acetylcysteine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACETYLCYSTEINE (ACETYLCYSTEINE)

Composition:

Active substance: acetylcysteine;

One tablet contains 200 mg of acetylcysteine;

Excipients: tartaric acid, citric acid, aspartame (E 951), sodium saccharin, lactose monohydrate, microcrystalline cellulose, crospovidone, magnesium stearate, polyethylene glycol, colloidal anhydrous silicon dioxide, peppermint oil.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, round, biconvex tablets with a minty odour. Speckles on the tablet surface are permissible.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. Acetylcysteine. ATC code R05CB01.

Pharmacological properties.

Pharmacodynamics.

Acetylcysteine is a mucolytic expectorant used to liquefy sputum in respiratory tract diseases associated with the production of thick mucus. Acetylcysteine is a derivative of the amino acid cysteine. The mucolytic effect of the drug is of chemical nature. Due to the presence of a free sulfhydryl group, acetylcysteine breaks the disulfide bonds of acidic mucopolysaccharides, leading to depolymerization of sputum mucoproteins, reduction of mucus viscosity, and facilitating expectoration and clearance of bronchial secretions. The drug retains its activity in the presence of purulent sputum.

Acetylcysteine also possesses antioxidant and pneumoprotective properties, which are due to the binding of chemical radicals by its sulfhydryl groups, thereby neutralizing them. Furthermore, the drug promotes increased synthesis of glutathione—a key factor in chemical detoxification. This characteristic of acetylcysteine enables its effective use in paracetamol overdose.

Pharmacokinetics.

After oral administration, acetylcysteine is rapidly and completely absorbed and undergoes hepatic metabolism to form cysteine, a pharmacologically active metabolite, as well as diacetylcysteine, cystine, and subsequently mixed disulfides. Bioavailability is very low—approximately 10%. Maximum plasma concentration is reached within 1–3 hours after administration. Plasma protein binding is approximately 50%. Acetylcysteine is excreted by the kidneys as inactive metabolites (inorganic sulfates, diacetylcysteine).

The elimination half-life is primarily determined by rapid biotransformation in the liver and is approximately 1 hour. In case of impaired liver function, the elimination half-life is prolonged up to 8 hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic diseases of the bronchopulmonary system requiring reduction of sputum viscosity, improvement of sputum expectoration and clearance.

Contraindications.

Hypersensitivity to acetylcysteine or to any of the other components of this medicinal product; gastric and duodenal ulcer in the stage of exacerbation, hemoptysis, pulmonary hemorrhage; liver, kidney, or adrenal gland diseases, severe exacerbation of bronchial asthma.

Interaction with other medicinal products and other forms of interactions.

Interaction studies have been conducted only in adults.

Combining this medicinal product with antitussive agents may suppress the cough reflex, thereby promoting dangerous accumulation of sputum; therefore, these drugs should not be used simultaneously.

The drug is pharmacologically incompatible with antibiotics and proteolytic enzymes. It reduces the absorption of penicillins, cephalosporins, tetracyclines, and aminoglycosides. The interval between their administration should be at least 2 hours. This does not apply to cefixime and loracarbef.

It is not recommended to dissolve acetylcysteine together with other drugs in the same glass.

Synergism between acetylcysteine and bronchodilators has been observed. Contact with metals or rubber leads to the formation of sulfides with a characteristic odor. There are data on enhancement of the vasodilatory and antithrombotic effects of nitroglycerin when used concomitantly with acetylcysteine.

Acetylcysteine reduces the hepatotoxic effect of paracetamol.

Activated charcoal reduces the efficacy of acetylcysteine.

Acetylcysteine can act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.

Concomitant administration of nitroglycerin and acetylcysteine may enhance the vasodilating effect of nitroglycerin. When simultaneous use is necessary, careful patient monitoring is required to detect hypotension promptly, which may be severe and may manifest as headache.

Laboratory parameters: acetylcysteine use may alter the results of quantitative colorimetric determination of salicylates and tests for ketones in urine.

Special precautions for use

Acetylcysteine should not be administered to patients with impaired liver or kidney function to prevent increased absorption of nitrogenous substances.

Isolated cases of skin reactions, such as Stevens-Johnson syndrome and Lyell's syndrome, have been observed following short-term exposure to acetylcysteine. If other skin or mucous membrane reactions occur, medical advice must be sought immediately and the drug should be discontinued promptly.

Patients with bronchial asthma should be under close medical supervision due to the possible development of bronchospasm. If bronchospasm occurs, treatment with acetylcysteine must be stopped immediately.

Caution is recommended when administering the drug to patients with a history of gastric or duodenal ulcer, especially when concomitantly taking other medications that irritate the gastric mucosa.

A mild sulfurous odor is not an indication of drug deterioration; it is characteristic of the active substance.

Mucolytic agents may cause bronchial obstruction in children under 2 years of age. Due to physiological characteristics of the respiratory system in this age group, the ability to clear respiratory secretions is limited. Therefore, mucolytics should not be used in children under 2 years of age.

Acetylcysteine affects histamine metabolism; therefore, prolonged therapy should not be prescribed to patients with histamine intolerance, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).

Administration of acetylcysteine results in the liquefaction of bronchial secretions. If the patient is unable to effectively expectorate sputum, postural drainage and bronchoaspiration may be required.

The drug contains aspartame, a phenylalanine derivative, which may be harmful to patients with phenylketonuria.

If the patient has known sensitivities to certain sugars, medical advice should be sought before taking this medication.

Use during pregnancy or breastfeeding

Clinical data on the effects of acetylcysteine in pregnant women are limited. There are no data available on its passage into breast milk. The drug should be prescribed during pregnancy or breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Ability to affect reaction speed when driving or operating machinery

There is no evidence that acetylcysteine affects the ability to drive or operate machinery.

Dosage and Administration

For adults and children aged 14 years and older: administer 400–600 mg of acetylcysteine per day, divided into 1–3 doses.

For children aged 6 to 14 years: administer 400–600 mg of acetylcysteine per day, divided into 2–3 doses.

For children aged 2 to 6 years: administer 200–400 mg of acetylcysteine per day, divided into 2 doses.

The medicinal product should be taken after meals. The tablet should be dissolved in a glass of water and consumed as quickly as possible. Additional fluid intake enhances the mucolytic effect of the drug.

The duration of treatment for chronic diseases is determined by the physician depending on the nature and course of the disease. For acute uncomplicated conditions, acetylcysteine should be used for 4–5 days.

Children: To be used in children aged 2 years and older.

Overdose

There are no reported cases of overdose with oral administration of acetylcysteine.

Symptoms: nausea, vomiting, diarrhea. In children, there is a risk of hypersalivation.

Treatment: symptomatic treatment.

Adverse reactions.

From the nervous system: headache.

From the organs of hearing and labyrinth: tinnitus.

From the respiratory system, thoracic and mediastinal disorders: dyspnea, bronchospasm — mainly in patients with hyperreactive bronchial system in case of bronchial asthma, rhinorrhea.

From the gastrointestinal tract: stomatitis, abdominal pain, nausea, vomiting, diarrhea, heartburn, dyspepsia, bad breath.

From the cardiovascular system: tachycardia, arterial hypotension.

From the blood and lymphatic system: anemia, hemorrhages; cases of bleeding during acetylcysteine use have been reported, sometimes due to hypersensitivity reactions. Various studies have demonstrated reduced platelet aggregation in the presence of acetylcysteine. The clinical significance of these findings has not yet been established.

General disorders: allergic reactions, including pruritus, urticaria, rash, exanthema, eczema, bronchospasm, angioneurotic edema, Quincke's edema, flush, anaphylactic/anaphylactoid reactions or even shock; there are also reports of severe skin reactions such as Stevens–Johnson syndrome and Lyell’s syndrome occurring during acetylcysteine treatment. In case of any changes in the skin or mucous membranes, medical advice should be sought immediately and acetylcysteine administration should be discontinued.

Reporting of adverse reactions. Reporting of suspected adverse reactions after marketing authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years from the date of manufacture of the drug in bulk packaging.

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

Keep out of reach of children.

Packaging. Tablets № 10×2 in blisters in a carton.

Supply category. Over-the-counter.

Manufacturer. Limited liability company "Pharmaceutical Company "Vertex".

Manufacturer's address and place of business.

33, Astronomichna Street, bld. "V-1", Kharkiv, Kharkiv region, 61085, Ukraine.