Fluimucil - antibiotic IT powder for infl + solvent N 3

Pharmacological properties of the drug Thiamphenicol glycinate acetylcysteinate

Thiamphenicol glycinate acetylcysteinate is a complex compound that combines the antibiotic thiamphenicol and the mucolytic acetylcysteine. Thiamphenicol has a wide spectrum of antibacterial action, is effective in vitro against bacteria that most often cause respiratory tract infections: gram-positive ( Streptococcus pneumoniae , Corynebacterium diphtheriae , Staphylococcus spp ., Streptococcus pyogenes, Str. faecalis, Listeria spp., Clostridium spp. ) and gram-negative ( Haemophilus influenzae, Neisseria, Salmonella, Escherichia coli, Shigella spp., Bordetella pertussis , Yersinia pestis, Brucella spp., Bacteroides spp .). The mechanism of action of thiamphenicol is bactericidal (suppresses the synthesis of cell wall peptoglycans). Acetylcysteine, by breaking the disulfide bonds of mucoproteins, quickly and effectively dilutes sputum and pus, reduces their viscosity and promotes discharge. Acetylcysteine ​​facilitates the penetration of the antibiotic thiamphenicol into lung tissue and inhibits the adhesion of bacteria to the epithelium of the respiratory tract. Thiamphenicol glycinate acetylcysteinate is rapidly distributed in the body and accumulates in the tissues of the respiratory tract in high therapeutic concentrations. The maximum concentration in the blood plasma is achieved 15 minutes after intramuscular administration; the half-life from the blood plasma is 1 hour with intravenous administration of thiamphenicol glycinate acetylcysteinate. Plasma protein binding is 50–60%. Metabolized in the liver, excreted in the urine, small amounts in bile and feces.

Thiamphenicol

Stylab / Catalog / Antibacterial drugs / Thiamphenicol

STYLAB offers test systems for the analysis of thiamphenicol in meat and other animal tissues, as well as in milk and milk powder using the ELISA method.

Thiamphenicol is a broad-spectrum antibiotic from the amphenicol group. Chemically, it is a derivative of chloramphenicol , in which the nitro group is replaced by a sulfo group. Thiamphenicol is active against steptococci, clostridia , Klebsiella, Neisseria, Shigella and many other bacteria, especially anaerobic ones. The mechanism of its action is due to the ability to inhibit protein synthesis in bacteria, which leads to stopping their reproduction. Thus, thiamphenicol exhibits a bacteriostatic and, in high concentrations, a bactericidal effect. In medicine, this antibiotic is prescribed for inhalation and rinsing cavities for respiratory diseases, and is also used to treat some sexually transmitted diseases. In veterinary medicine, thiamphenicol is used to treat respiratory and gastrointestinal infections in calves, pigs and poultry. In the Russian Federation, preparations containing this antibiotic are not registered for veterinary use.

In studies on rats, following oral administration, the highest concentrations of thiamphenicol are created in the liver and kidneys, as well as in the thyroid and pancreas, lungs, spleen and thymus. A similar distribution is observed in cows. With a single intravenous administration in rats, the half-life of thiamphenicol is about 50 minutes. In sheep, with four injections every 8 hours, it was approximately 1.5 hours. From mammals, thiamphenicol is mainly excreted unchanged by the kidneys and, to a lesser extent, in feces. However, a metabolite of this antibiotic, thiamphenicol gluconurate, is also released in pigs and rats. Thiamphenicol is poorly soluble in water, but soluble in fats. This determines its ability to penetrate into milk and accumulate in adipose tissue.

Thiamphenicol irritates the skin and mucous membranes upon contact with them, including when this substance is inhaled. Its use may cause allergic skin reactions in sensitive people. The LD50 of thiamphenicol for humans and other mammals is low: for example, for rats when administered orally, it exceeds 5 g/kg body weight. When administered intravenously, the toxicity of thiamphenicol is higher: LD50 for rats was 339 mg/kg body weight. In case of an overdose of thiamphenicol, nausea and vomiting are noted.

Unlike chloramphenicol, thiamphenicol does not cause aplastic anemia in humans. In an experiment on rats, when exposed to this antibiotic for 13 weeks at a dosage of 20.8 mg/kg body weight, the animals noted a decrease in body weight, a decrease in the content of erythrocytes and hemoglobin in the blood, a decrease in hematopoiesis in the bone marrow, and an increase in the relative weight of the liver and kidneys , a decrease in the relative mass of the thymus and, in males, testicular damage and decreased spermatogenesis. A similar effect, with the exception of damage to the testicles, was observed in experiments on dogs. The effect of thiamphenicol is reversible: 2 months after the end of the study, no deviations of the studied parameters from the norm were observed in the animals.

In studies on rats, thiamphenicol did not exhibit embryotoxic properties. However, at doses of 40 mg/kg body weight, this antibiotic was toxic to pregnant rabbits. Under the influence of thiamphenicol, a decrease in body weight was also observed in rabbit embryos. It is therefore assumed that this substance may be embryotoxic. Thiamphenicol did not exhibit mutagenic or genotoxic properties in studies in both bacteria and cell cultures. It did not demonstrate carcinogenic properties, however, there is insufficient data to make definitive conclusions regarding the carcinogenicity of thiamphenicol.

In the Russian Federation and the EAEU countries, the content of thiamphenicol in food raw materials and finished products is limited by TR CU 034/2013 “On the safety of meat and meat products.” According to it, products obtained from all types of animals should not contain more than 0.05 mg/kg of the amount of thiamphenicol and its conjugates.

STYLAB offers test systems for the analysis of thiamphenicol in meat, milk and milk powder using the ELISA method. They allow you to quickly screen large numbers of samples and do not require expensive equipment.

Literature

1. Thiamphenicol glycinate acetylcysteinate. Register of medicines in Russia.
2. Thiamphenicol. PubChem
3. Committee For Veterinary Medical Products. Thiamphemicol. (Extension to pigs and extrapolation to all food producing species). Summary Report (6). EMEA/CVMP/162614/2006-FINAL May 2006

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Indications for use of the drug Thiamphenicol glycinate acetylcysteinate

Infectious and inflammatory diseases of the respiratory tract, caused by sensitive microorganisms and accompanied by the accumulation of viscous secretions. Otolaryngology: catarrhal otitis, sinusitis, laryngotracheitis, prevention and treatment of obstructive and infectious complications of tracheostomy, preparation for bronchoscopy, bronchoaspiration. Therapy: acute and chronic bronchitis, prolonged pneumonia, lung abscess, emphysema, bronchiectasis, cystic fibrosis. Surgery: prevention and treatment of bronchopulmonary complications after thoracic surgery (bronchopneumonia, atelectasis). Phthisiology: bronchitis associated with pulmonary tuberculosis, retention of discharge due to insufficient drainage of cavernous lesions. Pediatrics: bronchitis and pneumonia, especially those that cannot be treated with other antibiotics, bronchiolitis, whooping cough, cystic fibrosis.

Fluimucil - antibiotic IT powder for infl + solvent N 3

Active substance: thiamphenicol, glycinate acetylcysteinate (thiamphenicol, glycinate acetylcysteinate)

Rec.INN Mod. WHO registered, modified name

Dosage form

The drug is available with a prescription Fluimucil®-Antibiotic IT

Lyophilisate for the preparation of solution for injection and inhalation

Release form, packaging and composition of the drug Fluimucil®-Antibiotic IT

Lyophilisate for the preparation of solution for injection and inhalation 1 fl.

thiamphenicol glycinate acetylcysteinate 810 mg,

 including thiamphenicol 500 mg

Excipients: disodium edetate.

Solvent: water for injection (4 ml).

810 mg - bottles (3) complete with solvent (amp. 3 pcs.) - plastic trays (1) - cardboard packs.

Clinical and pharmacological group: Antibiotic in combination with a mucolytic and antioxidant

Pharmacotherapeutic group: Combined antibiotic (antibiotic + mucolytic)

pharmachologic effect

Thiamphenicol glycinate acetylcysteinate is a complex compound that combines the antibiotic thiamphenicol and the mucolytic acetylcysteine. After absorption of thiaminephenicol, glycinate acetylcysteinate is split into acetylcysteine ​​and thiamphenicol.

Thiamphenicol is a derivative of chloramphenicol, the mechanism of action is associated with inhibition of bacterial cell protein synthesis. Thiamphenicol has a wide spectrum of antibacterial action and is effective in vitro against bacteria that most often cause respiratory tract infections: gram-positive (Streptococcus pneumoniae, Corynebacterium diphtheriae, Staphylococcus spp., Streptococcus pyogenes, Listeria spp., Clostridium spp.) and gram-negative (Haemophilus influenzae, Neisseria spp., Salmonella spp., Escherichia coli, Shigella spp., Bordetella pertussis, Yersinia pestis, Brucella spp., Bacteroides spp.).

Acetylcysteine, by breaking the disulfide bonds of mucoproteins, quickly and effectively dilutes sputum and pus, reduces their viscosity and promotes discharge. Acetylcysteine ​​facilitates the penetration of the antibiotic thiamphenicol into lung tissue and inhibits the adhesion of bacteria to the epithelium of the respiratory tract.

Pharmacokinetics

Thiamphenicol is rapidly distributed in the body, accumulates in the tissues of the respiratory tract in therapeutic concentrations (tissue/plasma concentration ratio is about 1). Cmax in plasma is achieved 1 hour after intramuscular administration. T1/2 is about 3 hours, Vd is 40-68 l. Plasma protein binding - up to 20%. It is excreted by the kidneys through glomerular filtration; 24 hours after administration, the amount of unchanged thiamphenicol in the urine is 50-70% of the administered dose. Penetrates through the placental barrier.

Acetylcysteine ​​is quickly distributed in the body after use, T1/2 is 2 hours. In the liver it is deacetylated to cysteine. In the blood, a mobile equilibrium of free acetylcysteine ​​and its metabolites (cysteine, cystine, diacetylcysteine) is observed, free and bound to plasma proteins. Acetylcysteine ​​penetrates into the intercellular space and is predominantly distributed in the liver, kidneys, lungs, and bronchial secretions. It is excreted by the kidneys in the form of inactive metabolites (inorganic sulfates, diacetylcysteine), a small part is excreted unchanged through the intestines. Penetrates through the placental barrier.

Indications of the active substances of the drug Fluimucil®-Antibiotic IT

diseases of the upper respiratory tract and ENT organs: exudative otitis media, sinusitis, laryngotracheitis;

diseases of the lower respiratory tract: acute and chronic bronchitis, prolonged pneumonia, lung abscess, emphysema, bronchiectasis, cystic fibrosis, bronchiolitis, whooping cough;

prevention and treatment of bronchopulmonary complications after thoracic surgery (bronchopneumonia, atelectasis);

prevention and treatment of obstructive and infectious complications of tracheostomy, preparation for bronchoscopy, bronchoaspiration;

with concomitant nonspecific forms of respiratory infections to improve drainage, including cavernous lesions, with mycobacterial infections.

Dosage regimen

The method of administration and dosage regimen of a particular drug depend on its release form and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular drug with the indications for use and dosage regimen should be strictly observed.

Injected intramuscularly and used for inhalations, applications, and cavity rinsing.

Inhalation: adults - 250 mg 1-2 times/day; children - 125 mg 1-2 times/day.

Endotracheal: through a bronchoscope, endotracheal tube, tracheostomy - 1-2 ml of solution (for adults, dissolve in 4 ml of water for injection - 500 mg of dry matter, for children - 250 mg).

Locally: for administration into the paranasal sinuses, as well as for washing cavities after surgical interventions in the area of ​​the nose and mastoid process, 1-2 ml of solution (for adults, dissolved in 4 ml of water for injection - 500 mg of dry matter, for children - 250 mg ).

For diseases of the nasopharynx and ear, instill 2-4 drops into each nasal passage or external auditory canal.

Intramuscularly: adults - 500 mg 2-3 times a day; children under 3 years old - 125 mg 2 times a day; 3-7 years - 250 mg 2 times a day; 7-12 years - 250 mg 3 times a day.

For premature and newborn babies up to 2 weeks, the average dose is 25 mg/kg/day.

If necessary, the dose can be increased by 2 times (in the first 2-3 days of treatment in particularly severe cases). Do not increase the dose in premature and newborn children, as well as in patients over 65 years of age.

The course of treatment is no more than 10 days.

Side effect

Possible: allergic reactions.

With intramuscular injection, a slight burning sensation at the injection site is possible, rarely - reticulocytopenia, anemia, leukopenia, neutropenia, thrombocytopenia.

With inhalation administration - reflex cough, local irritation of the respiratory tract, stomatitis, rhinitis, nausea. Bronchospasm is possible, in which case bronchodilators are prescribed.

Contraindications for use

anemia;

leukopenia;

thrombocytopenia;

hypersensitivity to one of the components of the drug.

With caution: with liver failure and chronic renal failure; in children of the first two years of life due to age-related characteristics of kidney function.

Use during pregnancy and breastfeeding

During pregnancy, the drug is prescribed only when the potential benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped during treatment.

Use for liver dysfunction

With caution in case of liver failure.

Use for renal impairment

With caution in chronic renal failure.

Use in children

With caution in children of the first two years of life due to age-related characteristics of kidney function.

Use in elderly patients

Do not increase the dose in patients over 65 years of age.

special instructions

During treatment, peripheral blood patterns should be monitored. If the number of leukocytes (less than 4 thousand/μl) and granulocytes (by more than 40%) decreases, the drug is discontinued.

The solution should not come into contact with metal and rubber surfaces.

Drug interactions

The simultaneous administration of antitussives may increase sputum stagnation due to suppression of the cough reflex.

It is not recommended to mix with other aerosol medications.

The algorithm for managing a patient with sinusitis/rhinosinusitis is described in specialized monographs, textbooks, and consent documents.

One of the main issues in the management of a patient with sinusitis/rhinosinusitis is the appropriateness of prescribing an antibacterial drug. Antibacterial therapy is indicated for moderate or severe forms of acute sinusitis, taking into account the suspected pathogen or their combination, and for mild forms - only in the case of recurrent upper respiratory tract infection and clinical symptoms lasting more than 5-7 days, as well as in the presence of severe concomitant somatic pathology and in immunocompromised patients. It is also recommended to prescribe local (topical) antibacterial therapy, both in combination with the systemic use of antibiotics, and as an alternative method of treating acute sinusitis (for any severity of sinusitis).

The purpose of the study, carried out at the clinical sites of the Department of Otorhinolaryngology, Pediatric Faculty, Federal State Autonomous Educational Institution of Higher Education, Russian National Research Medical University named after. N.I. Pirogov, the effectiveness of the inhalation method of administration of the complex drug thiamphenicol glycinate acetylcysteinate was assessed in comparison with an orally prescribed systemic antibiotic in the complex treatment of children with acute uncomplicated rhinosinusitis in an outpatient setting. The composition of the study drug includes thiamphenicol, which is active against the most significant bacterial pathogens in the etiology of sinusitis (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus), including those resistant/multiresistant to natural and semi-synthetic penicillins and N-acetylcysteine, which has a mucolytic effect .

We observed 61 patients (33 boys and 28 girls) aged from 3 to 9 years who contacted an otorhinolaryngologist on an outpatient basis with complaints of nasal congestion/discharge (more than 7 days and less than 12 weeks) and the presence of clinical and radiological signs of sinusitis. Patients of the main group (Group 1) received thiamphenicol glycinate acetylcysteinate (0.125 mg per inhalation 2 times a day), and patients of the 2nd group (comparison group) received amoxicillin clavulanate in an age-specific dosage.

According to the results of the study, there were no statistically significant differences between the groups in assessing the therapeutic effect of the drugs and in the duration of the course of treatment.

However, in group 1, the total number of medications taken ranged from 2 to 3, in group 2 – from 3 to 4 (p <0.001). Patients of group 2 took a topical decongestant, a solution of sea water for intranasal use and, unlike patients of group 1, a mucoactive drug (or a complex drug with a mucoactive effect).

Thus, the authors conclude that the use of inhaled thiamphenicol glycinate cysteinate is as effective as amoxicillin clavulanate in the treatment of children with acute uncomplicated rhinosinusitis.

The advantage of prescribing thiamphenicol glycinate acetylcysteinate in the complex treatment of uncomplicated rhinosinusitis in children can be considered a reduction in the need to take additional medications (p <0.001).

Source: Bogomilski M.R., Radtsig E.Yu., Pivneva N.D., Kuyanova V.E. The effectiveness of the drug thiamphenicol glycinate acetylcysteinate in the inhalation treatment of children with rhinosinusitis. Ros Vestn Perinatol and Pediatrician 2021; 66:(1): 73–79.