Acetal c

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACETAL C

Composition:

Active substance: acetylcysteine;

One sachet contains 100 mg, 200 mg, or 600 mg of acetylcysteine;

Excipients: ascorbic acid; orange flavor containing maltodextrin, gum arabic, ascorbic acid, alpha-tocopherol, sulfur dioxide (E 220); sugar, powdered.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white or off-white powder with a fruity odor.

Pharmacotherapeutic group. Mucolytic agents. ATC code: R05CB01.

Pharmacological Properties

Pharmacodynamics

N-acetyl-L-cysteine (NAC) exerts a pronounced mucolytic effect on mucous and mucopurulent secretions by depolymerizing mucoprotein complexes and nucleic acids that contribute to the viscosity of hyaline and purulent components of sputum and other secretions. Other properties include reduction of induced hyperplasia of mucocytes, increased surfactant production due to stimulation of type II pneumocytes, and stimulation of mucociliary apparatus activity, thereby improving mucociliary clearance.

NAC also exerts a direct antioxidant effect due to the presence of a nucleophilic free thiol (SH) group capable of directly interacting with electrophilic groups of reactive oxygen species. NAC protects α-1-antitrypsin—an enzyme that inhibits elastase—from inactivation by hypochlorous acid (HOCl), a potent oxidizing agent produced by myeloperoxidase, an enzyme of activated phagocytes.

Moreover, the molecular structure of NAC enables it to easily penetrate cellular membranes. Inside the cell, NAC is deacetylated to form L-cysteine—an essential amino acid for glutathione synthesis. As a glutathione precursor, NAC exerts an indirect antioxidant effect. Glutathione is a highly active tripeptide widely distributed in various animal tissues and is essential for maintaining cellular functional capacity and morphological integrity. It is part of the most important intracellular defense mechanism against both exogenous and endogenous reactive oxygen species and certain cytotoxic substances, including paracetamol.

Paracetamol exerts cytotoxic effects by progressively depleting glutathione levels. NAC plays a crucial role in maintaining adequate glutathione levels, thereby enhancing cellular protection. As a result, NAC is the specific antidote in paracetamol poisoning.

In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg NAC daily for 6 weeks led to a significant increase in inspiratory volume and forced vital capacity (FVC), possibly due to reduced air trapping.

In patients with idiopathic pulmonary fibrosis (IPF), oral administration of NAC at 600 mg three times daily for 1 year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve vital lung capacity (VLC) and diffusing capacity of the lungs for carbon monoxide measured by the single-breath method.

When administered as inhalation therapy for 1 year, NAC contributed to a reduction in the progression rate of the disease in patients with IPF.

When administered to patients with cystic fibrosis at very high doses (up to 3000 mg daily for 4 weeks), NAC did not produce significant toxic effects.

The antioxidant efficacy of NAC is associated with a marked reduction in elastase activity in sputum, which is the most significant indicator of lung function in patients with cystic fibrosis. In addition, during treatment, a decreased concentration of neutrophils in the airways was observed, including a reduction in the number of neutrophils actively releasing elastase-rich granules.

Pharmacokinetics

Absorption. After oral administration in humans, NAC is completely absorbed. Due to metabolism in the intestinal wall and the first-pass effect, the bioavailability of NAC after oral administration is very low (approximately 10%). No differences have been observed among various dosage forms. In patients with various respiratory and cardiovascular diseases, maximum plasma concentration of NAC is reached within 1–3 hours after administration and remains elevated for up to 24 hours.

Distribution. NAC is distributed in the body both in unchanged form (20%) and as metabolites (active) (80%). It is predominantly found in the liver, kidneys, lungs, and bronchial secretions. The volume of distribution of NAC ranges from 0.33 to 0.47 L/kg. Plasma protein binding is approximately 50% at 4 hours after administration, decreasing to 20% by 12 hours.

Metabolism and Excretion. After oral administration, NAC is rapidly and extensively metabolized in the intestinal wall and liver. The metabolite cysteine is considered active. NAC and cysteine are further metabolized via the same pathway. Approximately 30% of the dose is excreted by the kidneys. The elimination half-life of NAC is 6.25 hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic diseases of the bronchopulmonary system associated with increased sputum production.

Paracetamol overdose.

Contraindications.

Hypersensitivity to any component of the medicinal product. Peptic ulcer of the stomach and duodenum in the stage of exacerbation, hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.

Interaction with other medicinal products and other types of interactions.

Data are available only on interactions in adults.

Concomitant use of AC with antitussive agents may enhance sputum retention due to suppression of the cough reflex; therefore, a precise diagnosis must be established before prescribing combination therapy with these agents.

Activated charcoal reduces the efficacy of AC.

When administered simultaneously with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, and aminoglycosides, possible interaction with the thiol group of AC may occur, leading to reduced activity of both agents. These data were obtained exclusively from in vitro experiments in which the respective substances were mixed. Nevertheless, for safety reasons, oral antibiotics should be administered separately, with an interval of at least 2 hours between administration of these drugs. This does not apply to cefixime and loracarbef.

It is not recommended to dissolve AC in the same glass with other medicinal products.

Concomitant use of nitroglycerin and AC may result in enhanced vasodilatory and antiplatelet effects of nitroglycerin.

Significant hypotension and dilation of the temporal artery have been observed during concomitant administration of nitroglycerin and AC. When simultaneous use of nitroglycerin and AC is necessary, patients should be monitored for hypotension, which may be severe, and should be warned about the possibility of headache.

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

Effect on laboratory tests. AC may interfere with colorimetric assays for salicylates and with determination of ketone bodies in urine.

Special precautions for use.

In very rare cases, severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) have been reported in association with the use of AC. In most of these cases, at least one other medicinal product is more likely to be the cause of the mucocutaneous syndrome. If any skin or mucous membrane lesions occur, patients should consult a physician and discontinue AC immediately (see also section "Adverse reactions").

Patients suffering from bronchial asthma require careful monitoring during treatment due to the possible development of bronchospasm. When emptying the sachet contents into a vessel during solution preparation, the powder may become airborne and irritate the nasal mucosa, potentially causing reflex bronchospasm. If bronchospasm occurs, AC treatment should be discontinued immediately.

AC should be administered with caution to patients with a history of gastric or duodenal ulcer, especially when concomitantly taking other medicinal products that irritate the gastric mucosa.

AC should be prescribed with caution in patients with liver or kidney disease to avoid accumulation of nitrogen-containing substances in the body.

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

The use of AC, particularly at the beginning of treatment, may cause bronchial secretion to become thinner and increase in volume. If the patient is unable to effectively expectorate sputum, postural drainage and bronchoaspiration may be necessary.

A mild sulfurous odor is not indicative of product deterioration but 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.

Sulfur dioxide may rarely cause hypersensitivity reactions and bronchospasm.

If a patient has known sugar intolerances, medical advice should be sought before taking this medicine. Due to the presence of sugar, the product may be harmful to teeth.

Information for diabetic patients. 1 sachet (100 mg AC) contains 2.88 g of sugar (0.24 bread units); 1 sachet (200 mg AC) contains 2.77 g of sugar (0.23 bread units); 1 sachet (600 mg AC) contains 2.32 g of sugar (0.19 bread units).

Use during pregnancy or breastfeeding.

Pregnancy. Clinical data on the use of AC in pregnant women are limited. In animal studies, no direct or indirect adverse effects on pregnancy, embryofetal development, labor, or postnatal development have been observed.

AC crosses the placenta and has been detected in umbilical cord blood.

There is also insufficient information on the ability of AC to cross the blood-brain barrier in humans.

Breastfeeding. There is no information available on the passage of AC into breast milk.

The medicinal product may be used during pregnancy or breastfeeding only after careful assessment of the benefit-risk ratio.

Fertility.

Data are lacking.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration

Adults: 400–600 mg per day, divided into 1–3 doses depending on clinical condition.

Children:

aged 2–6 years: 200–400 mg per day, divided into 1–3 doses;

aged 6–14 years: 400–600 mg per day, divided into 1–3 doses;

aged 14 years and older: adult doses.

Dissolve the contents of the sachet in ½ glass of water, juice, or cold tea immediately before administration.

The duration of treatment is determined individually by the physician depending on the nature of the disease (acute or chronic).

Paracetamol overdose. Within the first 10 hours after ingestion of a toxic dose, the medicinal product should be administered as soon as possible at a dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 1–3 days.

The preparation must be administered without delay, immediately after preparing the solution.

Children.

100 mg or 200 mg powder: for children aged 2 years and older.

600 mg powder: for children aged 14 years and older.

Overdose.

There are no data on cases of overdose with oral dosage forms of AC.

No serious adverse effects were observed after administration of 11.6 g of AC per day for 3 months.

AC, when administered at doses of 500 mg/kg/day, does not cause signs or symptoms of overdose.

Clinical experience with intravenous administration of AC in paracetamol overdose has been obtained in humans using maximum daily doses of up to 30 g of AC.

Symptoms. Overdose may manifest with gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Children are at risk of hypersecretion.

Treatment. There is no specific antidote for AC poisoning; treatment is symptomatic.

Adverse Reactions

To assess the frequency of adverse reactions, the following classification is used: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Immune system disorders

Uncommon: hypersensitivity reactions.

Rare: anaphylactic shock, anaphylactic/anaphylactoid reactions.

Blood and lymphatic system disorders

Frequency not known: anemia.

Nervous system disorders

Uncommon: headache.

Ear and labyrinth disorders

Uncommon: tinnitus.

Cardiac disorders

Uncommon: tachycardia.

Vascular disorders

Rare: hemorrhages.

Chest and mediastinum disorders

Rare: bronchospasm, dyspnea.

Respiratory system disorders

Rare: rhinorrhea.

Gastrointestinal disorders

Uncommon: stomatitis, abdominal pain, vomiting, nausea, diarrhea.

Rare: dyspepsia.

Frequency not known: unpleasant breath odor.

Skin and subcutaneous tissue disorders

Uncommon: urticaria, rash, Quincke's edema, pruritus.

Frequency not known: eczema.

General disorders and administration site conditions

Uncommon: hyperthermia.

Frequency not known: facial swelling.

Investigations

Uncommon: decrease in blood pressure.

In very rare cases, severe skin reactions such as Stevens–Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) have been reported following the use of AC. In most of these cases, at least one other medicinal product was more likely to have caused the mucocutaneous syndrome.

Therefore, if any skin or mucous membrane lesions occur, medical advice should be sought immediately and administration of AC should be discontinued promptly.

Additionally, very rare cases of bleeding during the use of AC have been reported, sometimes due to hypersensitivity reactions.

Cases of decreased platelet aggregation have been observed; however, the clinical significance of this finding has not been established.

Shelf life. 3 years.

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

Keep out of reach of children.

Incompatibility. When dissolving AC, glassware should be used; avoid contact with metal and rubber surfaces.

It is not recommended to dissolve AC together with other medicinal products in the same glass.

Packaging. 3 g in sachets, pack of 1×10 or paired sachets pack of 2×5 in a box.

Dispensing category. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

22 Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.