Rapira 200 powder for oral solution 200 mg sachet 1 g No. 20

Instructions for Rapira 200 powder for oral solution 200 mg sachet 1 g No. 20

Composition

active ingredient: acetylcysteine;

1 sachet contains 200 mg of acetylcysteine;

excipients: sorbitol (E 420), aspartame (E 951), riboflavin (E 101), orange flavoring.

Dosage form

Powder for oral solution.

Main physicochemical properties: light yellow powder with a cream tint, without foreign mechanical inclusions with a characteristic orange, slightly sulfurous odor.

Pharmacotherapeutic group

Mucolytic agents.

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.

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. 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, has 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 COPD, administration of 1200 mg of AC per day for 6 weeks resulted in significant increases in inspiratory volume and forced vital capacity (FVC), 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 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, 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, 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 and excretion

After oral administration, AC 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 route. 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

Known hypersensitivity to acetylcysteine or any of the excipients.

Gastric and duodenal ulcer in the acute stage, hemoptysis, pulmonary hemorrhage.

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.

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 taking these drugs should be at least 2 hours. This does not apply to cefixime and 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, and they should be warned about the possibility of headaches.

Acetylcysteine can be a cysteine donor and increase glutathione levels, which helps detoxify oxygen free radicals and certain toxic substances in the body.

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 drug, but 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.

Rapira® 200 contains aspartame, a source of phenylalanine. This should be taken into account in patients with phenylketonuria.

The medicine contains sorbitol, therefore patients with hereditary fructose intolerance should not take this medicine.

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 penetration into breast milk.

The drug should be taken during pregnancy and 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

400–600 mg per day, divided into 1–3 doses, depending on clinical conditions.

Children

2–6 years: 200–400 mg per day, divided into 1–3 doses;

6–18 years: 400–600 mg per day, divided into 1–3 doses.

To obtain the required single dose, use the drug in the appropriate dosage.

Dissolve the powder in 1/3 cup of water.

The duration of the treatment course is determined by the doctor individually, depending on the nature of the disease (acute or chronic).

Paracetamol overdose

In the first 10 hours after ingestion of a toxic substance, take Rapira® 200 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® 200 should be taken immediately after preparation of the solution.

Children

Use in children from 2 years of age.

Overdose

There are no data on cases of overdose of medicinal forms of acetylcysteine intended for oral administration.

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

Acetylcysteine, when administered 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 following are adverse reactions after the use of acetylcysteine for oral administration.

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 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 has not been determined.

Expiration date

2 years.

Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

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 with other drugs in the same glass.

Packaging

Powder for oral solution 200 mg/1 g in sachets. 10 or 20 sachets in a cardboard box.

Vacation category

Without a prescription.

Producer

JSC "Farmak".

Location of the manufacturer and its business address

Ukraine, 04080, Kyiv, Kyrylivska St., 74.