Euromycin granules for oral solution 3 g sachet 8 g No. 1

Instructions for use: Euromycin granules for oral solution 3 g, sachet 8 g No. 1

Composition

active ingredient: fosfomycin;

1 sachet contains 5.631 g of fosfomycin trometamol, which is equivalent to 3.0 g of fosfomycin;

excipients: lemon flavoring, sodium saccharin (E 954), sucrose.

Dosage form

Granules for oral solution.

Main physicochemical properties: white granular powder. After dissolution, a characteristic citrus aroma is felt.

Pharmacotherapeutic group

Antimicrobials for systemic use. Other antimicrobials. Fosfomycin.

ATX code J01X X01.

Pharmacological properties

Euromycin contains the active ingredient fosfomycin in the form of fosfomycin trometamol salt. Fosfomycin is a bactericidal antibiotic (a derivative of phosphonic acid). It inhibits the synthesis of the bacterial cell wall by blocking one of the first steps in peptidoglycan synthesis.

Pharmacodynamics.

Euromycin contains fosfomycin [mono (2-amino-2-hydroxymethyl-1,3-propanediol) (2R-cis)-(3-methyloxiranyl) phosphonate], an antibiotic derived from phosphonic acid and used to treat urinary tract infections.

Fosfomycin affects the first stage of bacterial cell wall synthesis.

The structure of fosfomycin is similar to that of phosphoenolpyruvate. That is why it inactivates the enzyme enolpyruvyl transferase, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with phosphoenolpyruvate, one of the first stages of bacterial cell wall synthesis. Fosfomycin also reduces the adhesion of bacteria to the epithelium of the bladder mucosa, which can be a provocative factor in the development of recurrent infections.

Table 1 presents the in vitro activity of fosfomycin trometamol against clinically isolated microorganisms. The minimum inhibitory concentration (MIC) was determined by the disk diffusion method using 200 μg fosfomycin trometamol disks. Microorganisms with a zone of complete inhibition > 16 mm in diameter (on Mueller-Hinton medium) were classified as susceptible (corresponding to 200 μg/mL).

Table 1

Resistance / cross-resistance

Fosfomycin remains effective against the most common bacteria found in urinary tract infections.

Only some bacteria can develop resistance. The resistance rate of E. coli, which causes uncomplicated urinary tract infections, is extremely low.

Most multidrug-resistant E. coli and other enterobacteria that produce extended-spectrum beta-lactamases (ESBLs) are susceptible to fosfomycin, as are most types of methicillin-resistant Staphylococcus aureus.

No cases of cross-resistance with other antibacterial agents have been reported to date. Cross-resistance is unlikely because fosfomycin differs from any other antibiotic in chemical structure and has a unique mechanism of action.

Clinical efficacy

Fosfomycin has a broad spectrum of antibacterial activity, including against most gram-positive and gram-negative microorganisms that cause urinary tract infections, as well as against strains that produce penicillinase.

In vivo resistance has been observed against Enterobacter spp., Klebsiella spp., Enterococci, Proteus mirabilis, Staph. aureus and Staph. saprophyticus.

In addition, Euromycin reduces the adhesion of bacteria to the epithelium of the bladder mucosa, which can be a provocative factor in the development of recurrent infections.

Pharmacokinetics.

Absorption

After oral administration, approximately 50% of fosfomycin trometamol is rapidly absorbed. After administration of 50 mg/kg body weight, tmax is 2–2.5 hours and Cmax is 20–30 μg/ml.

Distribution

The binding of fosfomycin to plasma proteins is very low (less than 5%). The volume of distribution is 1.5–2.4 l/kg body weight.

Fosfomycin crosses the placental barrier and is excreted in breast milk.

Metabolism

Fosfomycin is not metabolized.

Selection

The plasma half-life is about 4 hours. After a single dose of 3 g of fosfomycin trometamol, urinary concentrations of 1800–3000 μg/ml are reached after 2–4 hours. Therapeutically effective concentrations (200–300 μg/ml) are maintained for up to 48 hours after administration. 40–50% of the dose is excreted in the urine in unchanged form during the first 48 hours.

In patients with renal insufficiency, drug elimination is slowed down in accordance with the degree of functional impairment, while the plasma half-life is increased (t1/2 up to 50 hours at creatinine clearance of 10 ml/min).

Indication

For the treatment of acute uncomplicated cystitis in women and girls aged 12 years and older.

For the prevention of infections in adult men undergoing transrectal prostate biopsy.

Official recommendations on the appropriate use of antibacterial agents should be considered.

Contraindication

Hypersensitivity to fosfomycin and other components of the drug, severe renal failure (creatinine clearance

Interaction with other medicinal products and other types of interactions

Concomitant administration with metoclopramide and other drugs that increase gastrointestinal (GI) motility reduces the absorption of Euromycin, which leads to a decrease in the concentration of fosfomycin in serum and urine.

If the drug is taken with food, plasma and urine fosfomycin levels are reduced. Therefore, it is recommended to take the drug on an empty stomach or 2–3 hours after eating or taking other medications.

Specific problems with INR (international normalized ratio) fluctuations. Numerous cases of increased antivitamin K antagonist activity have been reported in patients taking antibiotics. Risk factors include: serious infections or inflammation, advanced age, and poor general health. In these cases, it is difficult to determine whether the INR change is related to the infectious disease or caused by the drug. However, there are certain classes of antibiotics that are more commonly associated with INR fluctuations, including: fluoroquinolones, macrolides, cyclines, cotrimoxazole, and some cephalosporins.

Interaction studies were conducted only in adults.

Application features

There is insufficient evidence of the effectiveness of Euromycin in children. Since the 3 g dosage is not intended for children under 12 years of age, Euromycin should not be used in this age group.

The use of fosfomycin may lead to the development of hypersensitivity reactions, including anaphylaxis and anaphylactic shock, which can be life-threatening (see section "Adverse reactions").

If such reactions occur, fosfomycin should be discontinued and fosfomycin should not be reintroduced in these patients. Appropriate treatment should be instituted.

The use of antibiotics, including fosfomycin trometamol, can cause diarrhea. The severity can range from mild diarrhea to fatal colitis. Severe, persistent and/or bloody diarrhea during or after antibiotic treatment (including after several weeks) may be a symptom of diarrhea caused by Clostridium difficile. Therefore, the possibility of this diagnosis should be considered in patients who develop severe diarrhea during or after taking fosfomycin trometamol. If the diagnosis is suspected or confirmed, appropriate treatment should be initiated immediately. In such cases, drugs that inhibit peristalsis are contraindicated.

Renal insufficiency: Fosfomycin urinary concentrations remain therapeutically effective for 48 hours if creatinine clearance is above 10 mL/min.

Persistent infections and male patients: In case of persistent infections, careful examination and re-evaluation of the diagnosis is recommended, as this is often associated with complications of urinary tract infections or the prevalence of resistant pathogens (e.g. Staphylococcus saprophyticus, see section 5.1). In general, urinary tract infections in male patients should be considered as complicated urinary tract infections for which this medicinal product is not indicated (see section 4.1).

Euromycin contains sucrose. Diabetics and those who must follow a diet should take into account that 1 sachet of Euromycin contains 2.213 g of sucrose. Euromycin should not be used in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency.

Use during pregnancy or breastfeeding

Pregnancy

The use of single doses for the treatment of urinary tract infections in pregnant women is not considered appropriate.

Animal studies do not indicate direct or indirect toxic effects with respect to pregnancy, embryonic development, fetal development and/or postnatal development.

There are only limited data on the safety of fosfomycin in pregnant women. These data do not indicate the development of birth defects or fetal/neonatal toxicity of fosfomycin.

During pregnancy, the use of the drug is possible if necessary, when the expected effect of therapy for the pregnant woman exceeds the potential risk to the fetus.

Lactation

Euromycin is excreted in breast milk even after a single dose. During breastfeeding, the use of the drug should be discontinued.

The ability to influence the reaction speed when driving vehicles or other mechanisms.

Euromycin may cause dizziness, which may affect your ability to drive or operate machinery.

Method of administration and doses

Treatment of acute uncomplicated cystitis

Adult women and girls aged 12 years and over with a body weight of 50 kg are prescribed 1 sachet of the drug (3 g) once a day.

Prevention of infections in adult men undergoing transrectal prostate biopsy

Men weighing 50 kg or more are prescribed 1 sachet (3 g) 3 hours before and 24 hours after the intervention.

Method of application

For oral use.

For the treatment of acute uncomplicated cystitis in women and girls aged 12 years and older, it should be taken on an empty stomach (approximately 2–3 hours before or 2–3 hours after a meal), preferably at bedtime and after emptying the bladder.

Dissolve the contents of the sachet in 1 glass of water and drink the prepared solution immediately.

Children.

It is used in girls aged 12 and over to treat acute uncomplicated cystitis.

The safety and effectiveness of fosfomycin in children under 12 years of age have not been established.

Overdose

Data on overdose of fosfomycin when administered orally are limited.

Symptoms: vestibular disorders, hearing loss, metallic taste in the mouth, and a general decrease in taste perception.

Cases of hypotension, severe drowsiness, electrolyte disturbances, thrombocytopenia, and hypoprothrombinemia have been reported with parenteral administration of fosfomycin.

Treatment: symptomatic and supportive therapy. It is recommended to drink plenty of fluids to increase diuresis.

Adverse reactions

The most common adverse reactions with a single dose of fosfomycin trometamol are gastrointestinal disturbances, mainly diarrhea. These phenomena are most often short-lived and resolve spontaneously.

The table lists adverse reactions that have been reported in clinical trials or known from post-marketing experience.

The frequency of side effects is determined as follows:

very common (≥ 1/10);

common (≥ 1/100 —

uncommon (≥ 1/1000 -

rarely (≥ 1/100 —

very rarely (

unknown (cannot be determined from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2

Reporting of suspected adverse reactions

Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the link: https://aisf.dec.gov.ua.

Expiration date

3 years.

Do not use after the expiration date.

Storage conditions

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

Keep out of reach of children.

Packaging

8 g of the drug (3 g of active ingredient) in a sachet. 1 or 2 sachets in a cardboard pack.

Vacation category

According to the recipe.

Producer

Public Joint Stock Company "Chempharmaceutical Plant "Chervona Zirka".

Location of the manufacturer and address of its place of business

61010, Ukraine, Kharkiv region, Kharkiv city, Hordienkivska street, building 1.