Instructions for Rapira Efertab 600 effervescent tablets 600 mg No. 10
Composition
active ingredient: acetylcysteine;
1 tablet contains 600 mg of acetylcysteine;
excipients: anhydrous citric acid, maltodextrin, sodium bicarbonate, orange flavoring, leucine, sodium saccharin.
Dosage form
Effervescent tablets.
Main physicochemical properties: white, round tablets with a flat surface.
Pharmacotherapeutic group
Mucolytics. 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 increase the viscosity of the vitreous 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.
N-acetyl-L-cysteine 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, thus enhancing cellular defense. As a result, AC is a specific antidote for paracetamol poisoning.
In patients with chronic obstructive pulmonary disease (COPD), administration of 1200 mg of AC per day for 6 weeks resulted in significant increases in inspiratory volume and FVC (forced vital capacity), possibly due to reduced air trapping.
In patients with idiopathic pulmonary fibrosis (IPF), the use of acetylcysteine orally 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 (VC) and lung diffusion 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 that actively secrete elastase-rich granules.
Pharmacokinetics.
Absorption
In humans, acetylcysteine is completely absorbed after oral administration. Due to metabolism in the intestinal wall and the first-pass effect, the bioavailability of acetylcysteine when taken orally 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 secretions. 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
After oral administration, AC is rapidly and extensively metabolized in the intestinal wall and liver. The formed metabolite, cysteine, is considered the active metabolite. Acetylcysteine and cysteine are further metabolized by the same pathway.
Breeding
About 30% of the dose is excreted by the kidneys. After oral administration, the half-life (T1/2) of AC is 6.25 (4.59–10.6) 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 any of the excipients.
Children under 12 years of age. However, the patient's age under 12 years is not a contraindication to use in the treatment of paracetamol overdose.
Interaction with other medicinal products and other types of interactions
Interaction studies were conducted only in adults.
The use of antitussives with acetylcysteine may increase sputum congestion due to suppression of the cough reflex.
Activated charcoal reduces the effectiveness of acetylcysteine.
Information on the inactivation of antibiotics by acetylcysteine has so far been obtained only in in vitro experiments with direct mixing of the substances. If it is necessary to use acetylcysteine and any oral drugs (including antibiotics) simultaneously, they should be taken at an interval of at least 2 hours. This does not apply to loracarbef.
Significant hypotension and temporal artery dilation have been reported with concomitant administration of nitroglycerin and acetylcysteine. If concomitant administration of nitroglycerin and acetylcysteine is necessary, patients should be monitored for hypotension, which may be severe. Patients should be warned of the possibility of headache.
Concomitant use of acetylcysteine and carbamazepine may result in a decrease in carbamazepine levels to subtherapeutic levels.
Impact on laboratory tests
Acetylcysteine may interfere with the colorimetric assay for 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.
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 medications that irritate the gastric mucosa.
Acetylcysteine should be administered with caution to patients with liver or kidney disease to avoid the accumulation of nitrogenous substances in the body.
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).
The use of acetylcysteine, especially at the beginning of treatment, may 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.
A slight sulfuric odor is not a sign of a change in the quality of the drug - it is specific to the active ingredient.
Mucolytics can cause bronchial obstruction in children under 2 years of age. Due to the physiological characteristics of the respiratory system in children of this age group, the ability to clear respiratory secretions is limited. Therefore, mucolytics should not be used in children under 2 years of age.
1 effervescent tablet of 600 mg contains 8.4 mmol (194.2 mg) of sodium. This should be taken into consideration if the patient is 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 reproductive toxicity.
As a precautionary measure, the use of Rapira® Efertab 600 should be avoided during pregnancy.
Before using the drug during pregnancy, the potential risks should be weighed against the expected benefits.
Breast-feeding
There is no information on the excretion of acetylcysteine and/or its metabolites 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 the use of Rapira® Efertab 600 taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effect of acetylcysteine on human fertility. Animal studies have not shown any harmful effects on human fertility when using the drug at recommended doses.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no evidence that acetylcysteine affects the ability to drive and use other mechanisms.
Method of administration and doses
Adults and children aged 12 and over
Dissolve a 600 mg effervescent tablet in 1/3 cup of water and take once a day.
The duration of the treatment course is determined individually by the doctor, depending on the nature of the disease (acute or chronic).
Paracetamol overdose
In the first 10 hours after taking the toxic substance, the drug "Rapira® Efertab 600" should be taken as soon as possible at a rate of 140 mg/kg, then at a rate of 70 mg/kg every 4 hours for 1–3 days.
"Rapira® Efertab 600" must be taken without delay, immediately after dissolution.
No interactions with food have been reported; there are no recommendations for use of the drug with respect to meals.
Children
Use in children over 12 years of age.
Overdose
Volunteers took 11.2 g of acetylcysteine per day for three months without experiencing any serious side effects.
Acetylcysteine, when used at a dose 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.
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 organ system and frequency of occurrence.
Within each group, adverse reactions are presented in order of decreasing seriousness.
| Organ systems | Adverse reactions |
| Uncommon (≥ 1/1000 - < 1/100) | Rare (≥ 1/10,000 - < 1/1,000) | Very rare (< 1/10,000) | Unknown (cannot be estimated from available data) |
| On the part of the immune system | Hypersensitivity | Anaphylactic shock, anaphylactic/anaphylactoid reactions | | |
| Blood and lymphatic system disorders | Anemia | | | |
| From the nervous system | Headache | | | |
| From the side of the organs of hearing and labyrinth | Tingle | | | |
| From the heart | Tachycardia | | | |
| From the vascular side | Hemorrhages | | | |
| From the side of the chest and mediastinum | Bronchospasm, dyspnea | | | |
| Respiratory system | Rhinorrhea | | | |
| Gastrointestinal tract | Vomiting, diarrhea, stomatitis, abdominal pain, nausea | Dyspepsia | Bad breath | |
| Skin and subcutaneous tissue disorders | Urticaria, rash, angioedema, pruritus | Eczema | | |
| General disorders and administration site conditions | Hyperthermia | Facial swelling | | |
| Research | Lowering 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. In most of the cases described, at least one other drug was more likely to have caused the mucocutaneous syndrome. Therefore, if any new changes appear on the skin or mucous membranes, acetylcysteine should be discontinued immediately and a doctor should be consulted.
Cases of decreased platelet aggregation have been reported, but the clinical significance of this has not been determined.
It is important to report adverse reactions after a medicine has been authorised. This allows the benefit/risk balance of the medicine to be monitored. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Expiration date
3 years.
Do not use the product after the expiration date indicated on the package.
Storage conditions
Keep the tube tightly closed.
This medicinal product does not require any special temperature storage conditions.
Keep out of 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 in the same glass with other drugs.
Packaging
10 tablets in a tube. 1 tube in a pack.
Vacation category
Without a prescription.
Producer
E-Pharma Trento S.P.A./ E-Pharma Trento SPA
Location of the manufacturer and its business address
Frazione Ravina - Via Provina, 2 - Trento (TN), Italy.
Applicant
JSC "Farmak"
Applicant's location
Ukraine, 04080, Kyiv, Kyrylivska St., 63.
