Ac-help

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AC-HELP (AC-HELP)

Composition:

Active ingredient: acetylcysteine;

One effervescent tablet contains 600 mg of acetylcysteine;

Excipients: citric acid, maltodextrin, sodium bicarbonate, orange flavoring, leucine, sodium saccharin.

Medicinal form: Effervescent tablets.

Main physicochemical properties: white, round tablets with a flat surface.

Pharmacotherapeutic group: Mucolytics. 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 hyperplasia of mucous cells, 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. Of particular interest is the fact that NAC prevents the inactivation of α-1-antitrypsin—an enzyme that inhibits elastase—by hypochlorous acid (HOCl), a potent oxidant produced by myeloperoxidase in activated phagocytes.

Furthermore, 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. In addition, as a precursor of glutathione, NAC demonstrates an indirect antioxidant effect. Glutathione is a highly active tripeptide widely distributed in animal tissues and essential for maintaining cellular functional capacity and morphological integrity. It constitutes a key component 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. Consequently, NAC serves as a specific antidote in paracetamol poisoning.

In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg NAC daily for 6 weeks resulted in 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 acetylcysteine at 600 mg three times daily for one year, in combination with standard IPF therapy (prednisolone and azathioprine), helped preserve vital capacity (VC) and diffusing capacity of the lungs measured by the single-breath carbon monoxide method.

When administered as inhaled therapy over one year, NAC contributed to a reduction in the progression rate of the disease in patients with IPF.

When used 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. Additionally, during treatment, a decrease in the number of neutrophils in the airways was observed, as well as a reduction in the number of neutrophils actively releasing elastase-rich granules.

Pharmacokinetics.

Absorption

In humans, acetylcysteine is completely absorbed after oral administration. 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%), primarily detected 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

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.

Elimination

Approximately 30% of the dose is excreted by the kidneys. After oral administration, the elimination half-life (T_1/2) of NAC is 6.25 (4.59–10.6) hours.

Clinical characteristics.

Indications.

A mucolytic agent for the treatment of acute and chronic diseases of the bronchopulmonary system accompanied by increased sputum production.

Treatment of paracetamol (acetaminophen) overdose.

Contraindications.

Hypersensitivity to acetylcysteine or any component of the drug. Active peptic ulcer of the stomach or duodenum, hemoptysis, pulmonary hemorrhage, bronchial asthma without sputum thickening.

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 antitussives with acetylcysteine may enhance sputum retention due to suppression of the cough reflex.

Activated charcoal reduces the effectiveness of acetylcysteine.

When used concomitantly with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, and aminoglycosides, interaction with the thiol group of acetylcysteine may occur, leading to reduced activity of both agents. Therefore, the interval between administration of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.

Significant hypotension and dilation of temporal arteries have been observed when nitroglycerin and acetylcysteine are administered simultaneously. If concomitant use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for potentially severe hypotension, and they should also be warned about the possibility of headache.

Acetylcysteine 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

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, 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 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 prescribed to patients with histamine intolerance, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, pruritus).

Administration 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 sputum, postural drainage and bronchoaspiration may be required.

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

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically sodium-free.

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 pregnancy, embryofetal development, parturition, or postnatal development.

Breastfeeding period

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

The drug should be used during pregnancy and breastfeeding only after careful assessment of the benefit-risk ratio.

Ability to influence reaction speed when driving vehicles or operating machinery

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

Dosage and Administration.

Adults and children over 12 years of age

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).

When dissolving acetylcysteine, a glass container must be used; contact with metal and rubber surfaces should be avoided. Do not mix other medications into this solution.

Paracetamol overdose

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

AC-HELP must be taken without delay, immediately after preparing the solution.

Children.

For use in children over 12 years of age.

Overdose.

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

Volunteers took 11.6 g of acetylcysteine per day for three months without developing any serious adverse effects.

Acetylcysteine 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; treatment is symptomatic.

Side effects.

The following side effects may occur after administration of acetylcysteine internally.

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 is more likely to have caused the mucocutaneous syndrome. Therefore, if any new skin or mucous membrane changes occur, a physician should be consulted immediately and acetylcysteine should be discontinued without delay.

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

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a tube, in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

E-FARMA TRENTO S.P.A./E-PHARMA TRENTO S.P.A.

Manufacturer's address and location of business activity.

Frazione Ravina – Via Provina, 2, 38123 Trento (TN), Italy/Frazione Ravina – Via Provina, 2, 38123 Trento (TN), Italy.