Acc® long

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACC®LONG

Composition:

Active substance: acetylcysteine;

One tablet contains 600 mg of acetylcysteine;

Excipients: citric acid anhydrous, sodium hydrogencarbonate, sodium carbonate anhydrous, mannitol (E 421), lactose anhydrous, ascorbic acid, sodium cyclamate, sodium saccharin, sodium citrate, blackcurrant flavour "B".

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white, round tablets with a score line, smooth surface, with a blackcurrant odour.

Pharmacotherapeutic group. Mucolytics. ATC Code: R05C B01.

Pharmacological properties.

Pharmacodynamics.

N-acetyl-L-cysteine (acetylcysteine, ACC) is a mucolytic and expectorant agent used to liquefy sputum in respiratory 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 its free sulfhydryl group, acetylcysteine breaks the disulfide bonds of acidic mucopolysaccharides, leading to depolymerization of sputum mucoproteins and reduction of mucus viscosity, thus 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. In addition, the drug promotes increased synthesis of glutathione – an important factor in intracellular protection not only against exogenous and endogenous oxidative toxins, but also against a number of cytotoxic substances. This characteristic of acetylcysteine allows its effective use in paracetamol overdose.

Effect on inflammatory processes

Depletion of GSH reserves often causes oxidative stress and inflammation. NAC is capable of normalizing disturbed cellular redox status by influencing cellular signaling pathways and transcription mechanisms sensitive to redox processes.

Effect on bacterial biofilm

In vitro studies have shown that N-acetylcysteine is able to inhibit the formation of bacterial biofilm and disrupt already formed biofilms.

Effect on frequency of exacerbations

Long-term use of acetylcysteine (over 3 months) may reduce the frequency of acute exacerbations in patients with chronic bronchitis.

Pharmacokinetics.

After oral administration, acetylcysteine is rapidly and completely absorbed. Acetylcysteine is metabolized in the liver and intestinal wall to the pharmacologically active metabolite cysteine, as well as to diacetylcystine, cystine, and other mixed disulfides.

Due to a significant first-pass effect, the bioavailability of orally administered acetylcysteine is only about 10%. Maximum plasma concentration is reached within 1–3 hours, with the maximum plasma concentration of the active metabolite cysteine being approximately 2 μg/mL. Protein binding of acetylcysteine is approximately 50%. Its distribution in the lungs is sufficiently high (48%).

After oral administration, the drug undergoes extensive first-pass metabolism in the intestinal wall and liver. Acetylcysteine and its metabolites are present in the human body in three different forms: partially in free form, partially bound to proteins via unstable disulfide bonds, and partially as an incorporated amino acid. Biotransformation primarily involves deacetylation; the drug and free NAC have relatively low bioavailability: approximately 10% in plasma and other body fluids such as bronchoalveolar lavage fluid. The elimination half-life from plasma is approximately 1 hour, mainly due to rapid biotransformation in the liver. In case of impaired liver function, the plasma elimination half-life may extend up to 8 hours.

More than one-third (38%) of orally administered acetylcysteine is excreted as inactive metabolites (inorganic sulfates, diacetylcystine) in urine.

In rats, acetylcysteine crosses the placenta and is detected in amniotic fluid. At 0.5, 1, 2, and 8 hours after oral administration of 100 mg/kg body weight of acetylcysteine, the concentration of the metabolite L-cysteine in the placenta and amniotic fluid exceeds the maternal plasma concentration.

No studies have been conducted on the ability of acetylcysteine to cross the placenta or enter breast milk, or on its effects on the embryo or newborn infant in humans.

No studies have been conducted on the ability of acetylcysteine to cross the blood-brain barrier in humans.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to acetylcysteine or to other components of the drug. Active gastric or duodenal ulcer, hemoptysis, pulmonary hemorrhage, severe exacerbation of asthma.

Interaction with other medicinal products and other types of interactions.

Interaction studies were conducted only in adults.

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

Activated charcoal reduces the effectiveness of acetylcysteine.

When used simultaneously 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 used concomitantly. If simultaneous use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for hypotension, which may be severe, and should 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.

Acetylcysteine reduces the hepatotoxic effect of paracetamol.

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

When in contact with metals or rubber, sulfides with a characteristic odor are formed; therefore, glassware should be used for dissolving the drug.

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

There have been isolated reports of severe skin reactions (Stevens-Johnson syndrome and Lyell's syndrome) associated with the use of acetylcysteine. Therefore, if any changes in the skin or mucous membranes occur, the drug should be discontinued immediately and medical advice should be sought regarding further use.

The drug should be administered with caution to patients with a history of gastric or duodenal ulcer, especially when other medications that irritate the gastric mucosa are taken concomitantly.

Acetylcysteine should be prescribed with caution to patients with bronchial asthma due to the potential risk of bronchospasm.

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

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

Effervescent tablets contain sodium compounds. One tablet contains 6.03 mmol (138.8 mg) of sodium. This should be taken into account by patients on a low-sodium or sodium-free diet.

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).

A mild sulfurous odor is not a sign of drug deterioration but is characteristic of the active substance.

The preparation contains lactose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not take ACC® Long.

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. Information regarding excretion into breast milk is lacking.

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

Ability to influence reaction rate while driving or operating machinery

Does not affect.

Dosage and Administration.

For adults and children aged 14 years and older: administer 600 mg (1 tablet) once daily.

For children under 14 years of age and in cases where the daily dose should be divided into several administrations, acetylcysteine should be used in another pharmaceutical form or appropriate dosage.

The medication should be taken after food. The tablet must be dissolved in a glass of water and the solution consumed as quickly as possible. In individual cases, due to the presence of the stabilizer—ascorbic acid (acidum ascorbicum)—in the formulation, the prepared solution may be left for approximately 2 hours before administration. Additional fluid intake enhances the mucolytic effect of the drug.

The duration of treatment is determined individually by a physician, depending on the nature of the disease (acute or chronic). The medication should not be taken for more than 4–5 days without consulting a doctor.

Children. For use in children aged 14 years and older.

Overdose.

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

Volunteers have taken 11.6 g of acetylcysteine per day for 3 months without experiencing any serious adverse effects.

Acetylcysteine does not cause overdose when used at doses of 500 mg/kg/day.

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

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

Adverse Reactions

The following classification is used to describe the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency not known (available data do not allow estimation of frequency).

Immune system disorders:
Uncommon – hypersensitivity;
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 and vascular disorders:
Uncommon – tachycardia, arterial hypotension;
Rare – hemorrhages.

Respiratory system disorders:
Rare – dyspnea, bronchospasm (mainly in patients with bronchial hyperreactivity associated with bronchial asthma);
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, angioedema (Quincke's edema), pruritus;
Frequency not known – exanthema, eczema, angioneurotic edema.

General disorders:
Uncommon – hyperthermia;
Frequency not known – facial swelling.

Very rare cases of severe skin reactions (Stevens-Johnson syndrome and Lyell's syndrome) have been reported. In most cases, at least one other medicinal product may be more likely responsible for the occurrence of these mucocutaneous syndromes. Therefore, if any new skin or mucosal changes occur, medical advice should be sought immediately and acetylcysteine should be discontinued without delay.

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

Shelf life: 3 years.

Storage conditions

Store in a dry place at temperatures not exceeding 30 °C.

Keep out of reach of children.

Packaging
10 or 20 tablets in a tube; 1 tube (10 × 1 or 20 × 1) in a cardboard box.

Authorization category: Over-the-counter (without prescription).

Manufacturer:

1. Salutas Pharma GmbH
2. Hermes Pharma GmbH

Manufacturer's address and place of business:

1. Otto-von-Guericke-Allee 1, 39179 Barleben, Germany
2. Hans-Urmiller-Ring 52, 82515 Wolfratshausen, Germany