Instructions for use Dvace long effervescent tablets 600mg No. 10
Composition
active ingredient: acetylcysteine;
1 effervescent tablet contains 600 mg of acetylcysteine;
excipients: maltodextrin, anhydrous citric acid, sodium bicarbonate, orange flavoring, leucine, sodium saccharin.
Dosage form
Effervescent tablets.
Main physicochemical properties: white, round tablets with a flat surface.
Pharmacotherapeutic group
Cough and cold remedies. Mucolytics. Acetylcysteine. ATX code R05C B01.
Pharmacological properties
Pharmacodynamics
N-acetyl-L-cysteine (AC) has a pronounced mucolytic effect on mucous and mucopurulent secretions due to the depolymerization of mucoprotein complexes and nucleic acids, which impart viscosity to the hyaline and purulent components of sputum and other secretions. Additional properties: reduction of induced mucocyte hyperplasia, increased surfactant production due to stimulation of type II pneumocytes, stimulation of the activity of the mucociliary apparatus, which contributes to the improvement of mucociliary clearance.
AC also exerts a direct antioxidant effect due to the presence of a nucleophilic free thiol group (SH), which is able to directly interact with electrophilic groups of oxidative radicals. Of particular interest is the fact that AC prevents the inactivation of a-1-antitrypsin, an enzyme that inhibits elastase, by hypochlorous acid (HOCl), a strong oxidant produced by myeloperoxidase of active phagocytes.
In addition, the molecular structure of AC allows it to easily penetrate cell membranes. Inside the cell, AC is deacetylated to form L-cysteine, an essential amino acid for the synthesis of glutathione. In addition, AC, which is a precursor of glutathione, exhibits an indirect antioxidant effect. Glutathione is a highly active tripeptide, widespread in various animal tissues and indispensable for maintaining the functional capacity of the cell and its morphological integrity. In fact, it is part of the most important intracellular mechanism of protection against oxidative radicals, both exo- and endogenous, and some cytotoxic substances, including paracetamol.
Paracetamol exerts its cytotoxic effect by progressively reducing glutathione levels. AC plays a primary role in maintaining adequate glutathione levels, enhancing cellular defense. As a result, AC is a specific antidote for paracetamol poisoning.
In patients with chronic obstructive pulmonary disease, administration of 1200 mg of AC per day for 6 weeks resulted in a significant increase in inspiratory volume and forced vital capacity, possibly due to a decrease in air trapping.
In patients with idiopathic pulmonary fibrosis (IPF), the use of acetylcysteine orally at a dose of 600 mg 3 times a day for one year in combination with standard IPF therapy (prednisolone and azathioprine) contributed to the preservation of vital capacity and lung diffusing capacity, measured by the single-breath carbon monoxide method.
In the form of inhalation therapy for one year, AC helped reduce the intensity of disease progression in patients with IPL.
When used in very high doses (up to 3000 mg daily for 4 weeks) in patients with cystic fibrosis, AC did not have a significant toxic effect.
The antioxidant efficacy of AC is associated with a marked decrease in sputum elastase activity, which is the most significant indicator of lung function in patients with cystic fibrosis. In addition, treatment was associated with a decrease in the number of neutrophils in the respiratory tract, as well as the number of neutrophils actively secreting elastase-rich granules.
Pharmacokinetics
Absorption
In humans, after oral administration, AC is completely absorbed. Due to metabolism in the intestinal wall and the first-pass effect, the bioavailability of acetylcysteine after oral administration is very low (approximately 10%). No differences were found for different dosage forms. In patients with various respiratory and cardiac diseases, the maximum concentration of AC in the blood plasma is reached 1–3 hours after administration and remains high for 24 hours.
Distribution
Acetylcysteine is distributed in the body both in unchanged form (20%) and in the form of metabolites (active) (80%), while it is mainly found in the liver, kidneys, lungs and bronchial secretion. The volume of distribution of AC is from 0.33 to 0.47 l / kg. Binding to plasma proteins is about 50% 4 hours after administration and decreases to 20% after 12 hours.
Metabolism and excretion
After oral administration, acetylcysteine is rapidly and extensively metabolized in the intestinal wall and liver. The formed metabolite, cysteine, is considered active. Further, acetylcysteine and cysteine are metabolized by the same pathway. About 30% of the dose is excreted by the kidneys. T1/2 AC is 6.25 hours.
Indication
Treatment of acute and chronic diseases of the bronchopulmonary system, accompanied by increased sputum production.
Paracetamol overdose.
Contraindication
Hypersensitivity to acetylcysteine or to other components of the drug. Gastric and duodenal ulcer in the acute stage, hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.
Interaction with other medicinal products and other types of interactions
Interaction studies were conducted only with adults.
The use of antitussives with acetylcysteine may increase sputum congestion due to a decrease in the cough reflex.
Activated charcoal reduces the effectiveness of acetylcysteine.
Acetylcysteine is pharmacologically incompatible with antibiotics and proteolytic enzymes. When used simultaneously with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, aminoglycosides, their interaction with the thiol group of acetylcysteine is possible, which leads to a decrease in the activity of both drugs. Therefore, the interval between the use of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.
With the simultaneous use of nitroglycerin and acetylcysteine, there are reports of significant hypotension and dilation of the temporal artery due to increased vasodilator and antithrombotic effects of nitroglycerin. If it is necessary to use nitroglycerin and acetylcysteine simultaneously, patients should be monitored for hypotension, which may be severe, and they should be warned about the possibility of headache. Acetylcysteine can be a cysteine donor and increase the level of glutathione, which helps detoxify free oxygen radicals and certain toxic substances in the body. Acetylcysteine reduces the hepatotoxic effect of paracetamol.
It is not recommended to dissolve acetylcysteine with other medications in the same glass. There is a synergism of acetylcysteine with bronchodilators.
Upon contact with metals or rubber, sulfides with a characteristic odor are formed, so glassware should be used to dissolve the medicine.
Impact on laboratory tests
Acetylcysteine may interfere with the results of colorimetric assays for the quantitative determination of salicylates and the determination of ketone bodies in urine.
Application features
Patients with bronchial asthma should be closely monitored during treatment due to the possible development of bronchospasm. In the event of bronchospasm, treatment with acetylcysteine should be discontinued immediately.
There are isolated reports of severe skin reactions (Stevens-Johnson and Lyell syndromes) when taking acetylcysteine, therefore, in the event of changes in the skin or mucous membranes, the use of the drug should be immediately discontinued and a doctor should be consulted regarding its further use.
It is recommended to use the drug with caution in patients with a history of gastric and duodenal ulcers, especially in case of concomitant use of other drugs that irritate the gastric mucosa.
Acetylcysteine should be prescribed with caution to patients with liver or kidney diseases to avoid the accumulation of nitrogen-containing substances in the body.
The use of acetylcysteine, especially at the beginning of treatment, can cause liquefaction of bronchial secretions and increase their volume. If the patient is unable to cough up sputum effectively, postural drainage and bronchoaspiration are necessary.
Acetylcysteine affects histamine metabolism, so long-term therapy should not be prescribed to patients with histamine intolerance, as this may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).
A slight sulfuric odor is not a sign of a change in the properties of the medicinal product, but is specific to the active substance.
Important information about excipients.
This medicinal product contains sodium compounds. Caution should be exercised when administered to patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
Pregnancy.
Clinical data on the use of acetylcysteine in pregnant women are limited. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
Breast-feeding.
There is no information on the excretion of acetylcysteine into breast milk.
The drug should be used during pregnancy or breastfeeding only after careful assessment of the benefit/risk ratio.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no evidence that acetylcysteine affects the ability to drive and use machines.
Method of administration and doses
Adults and children aged 12 and over
Dissolve 600 mg effervescent tablets in 1/3 cup of water and take once a day.
Additional fluid intake enhances the mucolytic effect of the drug.
The duration of the course of treatment is determined by the doctor individually, depending on the nature of the disease (acute or chronic). The drug should not be taken for more than 4–5 days without consulting a doctor.
In the first 10 hours after ingestion of a toxic substance, take acetylcysteine at a rate of 140 mg/kg as soon as possible, then at a rate of 70 mg/kg every 4 hours for 1–3 days.
Acetylcysteine should be taken without delay, immediately after preparing the solution.
Children
Use for children over 12 years of age.
Overdose
There are no reports of overdose with oral acetylcysteine. Volunteers have taken 11.6 g of acetylcysteine per day for 3 months without any serious side effects.
Acetylcysteine, when administered in doses of 500 mg/kg/day, does not cause overdose. Symptoms: Overdose may manifest as gastrointestinal symptoms such as nausea, vomiting and diarrhea.
Treatment. There is no specific antidote for acetylcysteine poisoning, therapy is symptomatic.
Side effects
All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (≥ 1/10,000 - < 1/1,000), rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
From the side of the organs of hearing and vestibular apparatus: infrequently - tinnitus.
Respiratory, thoracic and mediastinal disorders: rarely - dyspnoea, bronchospasm (mainly in patients with bronchial hyperreactivity associated with bronchial asthma); frequency unknown - rhinorrhea.
Gastrointestinal: infrequently - vomiting, diarrhea, stomatitis, abdominal pain, nausea, heartburn; rarely - dyspepsia; frequency unknown - bad breath.
From the nervous system: infrequently - headache.
Cardiac disorders: infrequently – tachycardia, arterial hypotension.
Vascular disorders: rare – hemorrhages.
Blood and lymphatic system disorders: frequency unknown - anemia; cases of bleeding have been reported during the use of acetylcysteine, sometimes due to hypersensitivity reactions.
Immune system disorders: uncommon – hypersensitivity; rare – anaphylactic shock, anaphylactic/anaphylactoid reactions.
Skin and subcutaneous tissue disorders: infrequently - urticaria, rash, angioedema, itching; frequency unknown - exanthema, eczema, angioedema.
General disorders and administration site conditions: uncommon – hyperthermia; frequency unknown – facial edema.
In very rare cases, there have been reports of individual severe skin reactions (Stevens-Johnson syndrome and Lyell's syndrome) in association with acetylcysteine. In most cases, at least one other drug is more likely to be the cause of the mucocutaneous syndrome. Therefore, if any new changes appear on the skin or mucous membranes, you should consult a doctor and immediately discontinue acetylcysteine.
Cases of decreased platelet aggregation have been reported, but the clinical significance of this is not known.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store in the original packaging, in a tightly closed tube, at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Incompatibility
When dissolving acetylcysteine, it is necessary to use glassware and avoid contact with metal and rubber surfaces.
It is not recommended to dissolve acetylcysteine with other medications in the same glass.
Antibiotics and acetylcysteine should not be mixed before administration due to the possibility of in vitro inactivation of antibiotics (mainly β-lactam antibiotics).
Packaging
10 tablets in a tube; 1 tube in a pack.
Vacation category
Without a prescription.
Producer
E-Pharma Trento S.p.A.
Location of the manufacturer and address of its place of business.
Frazione Ravina - Via Provina, 2 - 38123 Trento (TN), Italy.
Applicant
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the applicant and address of the place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
