Astrace

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AstraCe® AstraCe

Composition:

Active substance: acetylcysteine;

1 sachet contains acetylcysteine 600 mg;

Excipients: ascorbic acid; sucrose; saccharin; orange flavor.

Pharmaceutical form. Oral solution powder.

Main physicochemical properties: white or almost white powder, without particle agglomeration, with a characteristic 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, which contribute to the viscosity of hyaline and purulent components of sputum and other secretions. Additional properties include reduction of induced mucocyte hyperplasia, increased surfactant production due to stimulation of type II pneumocytes, and stimulation of mucociliary apparatus activity, thereby improving mucociliary clearance.

N-acetyl-L-cysteine 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 radicals. NAC prevents inactivation of α-1-antitrypsin—the enzyme that inhibits elastase—by hypochlorous acid (HOCl), a potent oxidant produced by myeloperoxidase in activated phagocytes.

Moreover, the molecular structure of NAC allows it to easily penetrate cell membranes. Inside the cell, NAC is deacetylated to form L-cysteine, an essential amino acid for glutathione synthesis. As a glutathione precursor, NAC also demonstrates 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, in fact, 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 serves as a specific antidote in paracetamol poisoning.

In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg of 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), administration of oral acetylcysteine at 600 mg three times daily for one year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve lung vital capacity (VC) and diffusing capacity of the lungs measured by the single-breath carbon monoxide method.

When used as inhalation therapy over one year, NAC contributed to reduced disease progression in patients with IPF.

When administered at very high doses (up to 3000 mg daily for 4 weeks) in patients with cystic fibrosis, 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 reduction was observed in the number of neutrophils in the airways, as well as in the number of neutrophils actively releasing elastase-rich granules.

Pharmacokinetics

Absorption

In humans, after oral administration, acetylcysteine is completely absorbed. Due to metabolism in the intestinal wall and first-pass effect, the bioavailability of acetylcysteine 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

Acetylcysteine is distributed in the body both in unchanged form (20%) and as metabolites (active) (80%), with predominant detection 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% four hours after administration and decreases to 20% after 12 hours.

Metabolism and Excretion

After oral administration, NAC is rapidly and extensively metabolized in the intestinal wall and liver. The resulting metabolite, cysteine, is considered active. Subsequently, both acetylcysteine and cysteine are metabolized via the same pathway. Approximately 30% of the dose is excreted by the kidneys. The half-life (T_1/2) 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.

Known hypersensitivity to acetylcysteine or to any of the excipients of the medicinal product.

Acute stage of gastric and duodenal ulcer, hemoptysis, pulmonary hemorrhage.

Children under 12 years of age. This is not a contraindication for use in the treatment of paracetamol overdose.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been conducted only in adults.

Concurrent use of acetylcysteine with antitussive agents may enhance sputum retention due to suppression of the cough reflex.

Activated charcoal reduces the effectiveness of acetylcysteine.

Data on antibiotic inactivation by acetylcysteine have so far been obtained only in in vitro experiments involving direct mixing of substances. If concomitant administration of acetylcysteine and any oral drugs (including antibiotics) is necessary, they should be taken at least 2 hours apart. This does not apply to loracarbef.

Concomitant administration of nitroglycerin and acetylcysteine has been shown to cause significant arterial hypotension and dilation of the temporal artery. In cases where concomitant use of nitroglycerin and acetylcysteine is required, patients should be monitored for arterial hypotension, which may be severe. Patients should be warned about the possibility of headache.

Concomitant use of acetylcysteine and carbamazepine may lead to subtherapeutic levels of carbamazepine.

Effect on laboratory tests

Acetylcysteine may interfere with colorimetric assays for salicylates and with the determination of ketone bodies in urine.

Special precautions for use

Patients with bronchial asthma should be under strict medical supervision during treatment with this medicinal product due to the possible development of bronchospasm. If bronchospasm occurs, acetylcysteine therapy should be discontinued immediately.

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

Acetylcysteine should be administered with caution to patients with hepatic or renal impairment to avoid accumulation of nitrogen-containing substances in the body.

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, pruritus).

The use of acetylcysteine, particularly at the beginning of treatment, may cause liquefaction of bronchial secretions and increase their volume. If the patient is unable to effectively expectorate mucus, postural drainage and bronchoaspiration may be required.

A mild sulfurous odor is not indicative of product deterioration but is characteristic of the active substance.

Use during pregnancy or breastfeeding

Pregnancy

Clinical data on the use of acetylcysteine in pregnant women are limited. Animal studies have not revealed any direct or indirect adverse effects on reproductive toxicity.

As a precautionary measure, the use of the medicinal product AstraTse®, powder for oral solution, should be avoided during pregnancy.

Before administering the drug during pregnancy, the potential risk should be weighed against the expected benefit.

Breastfeeding period

There is no information available on the passage of acetylcysteine and/or its metabolites into breast milk. The risk to the infant cannot be excluded.

A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from using the medicinal product AstraTse®, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Fertility

There are no data on the effect of acetylcysteine on human fertility. Animal studies have not revealed any harmful effect on fertility in humans when the drug is used at recommended doses.

Ability to affect reaction speed when driving or operating machinery

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

Method of Administration and Dosage

Adults and children aged 12 years and older

Dissolve 1 sachet of 600 mg in 1/3 glass of water and take once daily.

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

Paracetamol overdose

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

The medicinal product AstraCe® must be taken immediately after dissolution without delay.

No interactions with food have been reported; there are no recommendations regarding administration in relation to food intake.

Children

Use in children aged 12 years and older.

Overdose

There are no data on cases of overdose with oral formulations of acetylcysteine.

Volunteers have taken 11.2 g of acetylcysteine per day for 3 months without any serious adverse reactions.

Acetylcysteine, when used at a dose of 500 mg/kg/day, does not cause overdose.

Symptoms

Overdose may manifest with gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

Treatment

There is no specific antidote in acetylcysteine poisoning; therapy is symptomatic.

Adverse reactions

The most common adverse reactions associated with oral administration of acetylcysteine are gastrointestinal reactions. Hypersensitivity reactions, including anaphylactic shock, anaphylactic/anaphylactoid reaction, bronchospasm, angioedema, rash, and pruritus, have been reported less frequently.

In the table below, adverse reactions are listed by system organ classes and frequency of occurrence: 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), and not known (cannot be estimated from available data).

Within each group, adverse reactions are listed in order of decreasing severity.

In very rare cases, severe skin reactions such as Stevens–Johnson syndrome and Lyell’s syndrome have been reported in connection with the use of acetylcysteine. In most cases, at least one other medicinal product may be more likely to have caused the mucocutaneous syndrome. Therefore, if any new skin or mucous membrane changes occur, medical advice must be sought immediately and administration of acetylcysteine should be discontinued without delay.

Cases of reduced platelet aggregation have been observed; however, the clinical significance of this finding is not known.

Reporting of suspected adverse reactions

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

Shelf life. 3 years.

Do not use the medicinal product 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 reach and sight of children.

Packaging. 3 g sachets; 10 sachets in a cardboard box.

Availability. Over-the-counter.

Manufacturer. ASTRAFARM LLC.

Address of manufacturer and location of its business activity.

6, Kyivska Street, Vyshneve, Buchanskyi district, Kyiv region, 08132, Ukraine.