Acetal soluble

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACETAL SOLUBLE (ACETAL SOLUBLE)

Composition:

Active substance: acetylcysteine;

1 tablet contains 600 mg of acetylcysteine;

Excipients: sodium hydrogen carbonate, citric acid, aspartame (E 951), lemon flavor containing maltodextrin; gum arabic (E 414); citric acid.

Pharmaceutical form. Effervescent tablets.

Main physico-chemical properties: white, round, flat-surfaced tablets with bevelled edges, having a characteristic lemon and slightly sulfurous odor. Effervescence (gas bubbles) is observed when dissolved in water. Slight opalescence and characteristic lemon with slightly sulfurous odor are acceptable.

Pharmacotherapeutic group. Mucolytics. ATC code R05C B01.

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 oxidative radicals. Particularly noteworthy is the fact that NAC prevents the inactivation of α1-antitrypsin—an 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 cellular membranes. Inside the cell, NAC is deacetylated to form L-cysteine, an essential amino acid for glutathione synthesis. In addition, as a precursor of glutathione, NAC exhibits an indirect antioxidant effect. Glutathione is a highly active tripeptide widely distributed in various animal tissues and essential for maintaining cellular functional capacity and morphological integrity. It is, in fact, a key component of the most important intracellular defense mechanism against oxidative radicals, both exogenous and endogenous, as well as against certain cytotoxic substances, including paracetamol.

Paracetamol exerts cytotoxic effects through progressive depletion of glutathione. 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 per day over 6 weeks led to a significant improvement in inspiratory volume and forced vital capacity (FVC), possibly due to reduced air trapping.

In patients with idiopathic pulmonary fibrosis (IPF), treatment with oral acetylcysteine at 600 mg three times daily for 1 year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve vital capacity (VC) 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 used in very high doses (up to 3000 mg daily for 4 weeks) in patients with cystic fibrosis, NAC did not cause 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 in the number of neutrophils in the airways was observed, as well as a decrease 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 distribution 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 and decreases to 20% at 12 hours.

Metabolism and Elimination. After oral administration, NAC is rapidly and extensively metabolized in the intestinal wall and liver. The resulting metabolite, cysteine, is considered active. Subsequently, acetylcysteine and cysteine are metabolized via the same pathway. Approximately 30% of the dose is excreted by the kidneys. The elimination half-life (T½) of NAC is 6.25 (4.59–10.6) hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic diseases of the bronchopulmonary system accompanied by increased mucus production.

Paracetamol overdose.

Contraindications.

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

Acute stage of gastric and duodenal peptic 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.

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

Activated charcoal reduces the effectiveness of acetylcysteine.

Information on inactivation of antibiotics by acetylcysteine has so far been obtained only from in vitro experiments with direct mixing of substances. When concomitant administration of acetylcysteine and any oral drugs (including antibiotics) is necessary, they should be taken at an interval of at least 2 hours. This does not apply to cefixime and loracarbef.

Significant arterial hypotension and dilation of the temporal artery have been observed during concomitant use of nitroglycerin and acetylcysteine. When concomitant use of nitroglycerin and acetylcysteine is required, patients should be monitored for arterial hypotension, which may be severe; they should also be warned about the possibility of developing 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 due to the possible development of bronchospasm. If bronchospasm occurs, treatment with acetylcysteine must be discontinued immediately.

The drug 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.

Acetylcysteine should be administered with caution in 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 administered to patients with histamine intolerance, as this may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).

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 necessary.

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

The medicinal product contains aspartame, a phenylalanine derivative, which may be harmful for patients with phenylketonuria.

This medicinal product contains 6.84 mmol (or 157.19 mg) of sodium per 600 mg dose. Caution is advised when administering to 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 have not revealed any direct or indirect adverse effects on reproductive toxicity.

As a precautionary measure, the use of the medicinal product during pregnancy should be avoided.

Before using the drug during pregnancy, the potential risks should be weighed against the expected benefits.

Breastfeeding period

There is no information available on the passage of acetylcysteine into breast milk. A 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, 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 effects 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 one effervescent tablet 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 the toxic substance, administer the drug as soon as possible at a dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 1–3 days.

The drug must be taken without delay, immediately after preparing the solution.

No interactions between the drug and food have been reported; there are no recommendations regarding administration in relation to food intake.

Children. For use in children aged 12 years and older.

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

It is known that volunteers took 11.2 g of acetylcysteine per day for 3 months without experiencing any serious adverse effects.

Acetylcysteine, when administered at doses 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 case of 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 reactions, bronchospasm, angioedema, rash, and pruritus, occurred less frequently.

The adverse reactions listed below are categorized by organ system 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 frequency not known (cannot be estimated from available data).

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

Immune system disorders:
Uncommon – hypersensitivity; very 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:
Very rare – hemorrhage.

Chest and mediastinal disorders:
Rare – bronchospasm, dyspnea.

Respiratory system disorders:
Frequency not known – rhinorrhea.

Gastrointestinal disorders:
Uncommon – vomiting, diarrhea, stomatitis, abdominal pain, nausea; rare – dyspepsia; frequency not known – unpleasant breath odor.

Skin and subcutaneous tissue disorders:
Uncommon – urticaria, rash, Quincke's edema (angioedema), pruritus; frequency not known – eczema.

General disorders and administration site conditions:
Uncommon – hyperthermia; frequency not known – facial swelling.

Investigations:
Uncommon – decreased blood pressure.

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

Cases of reduced platelet aggregation have been reported, but the clinical significance of this finding is not established.

Reporting of Adverse Reactions

Reporting suspected adverse reactions after a medicinal product has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf Life. 2 years.

Storage Conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach and sight of children.

Packaging. Effervescent tablets: No. 10 (2x5), No. 20 (2x10) in a strip pack within a carton.

Availability Category. Over-the-counter (without prescription).

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's Address and Place of Business. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, 22.