Urofoscin granules for oral solution 3 g sachet No. 1

Instructions Urofoscin granules for oral solution 3 g sachet No. 1

Composition

active ingredient: fosfomycin;

1 sachet contains 5.631 g of fosfomycin trometamol, which is equivalent to 3 g of fosfomycin;

excipients: orange flavoring, tangerine flavoring, saccharin, sucrose.

Dosage form

Granules for oral solution.

Main physicochemical properties: white or almost white granular powder with a characteristic smell of tangerine flavoring.

Pharmacotherapeutic group

Antimicrobials for systemic use. Other antimicrobials.

ATX code J01X X01.

Pharmacological properties

Urofoscin contains the active substance fosfomycin in the form of fosfomycin trometamol salt. Fosfomycin is a bactericidal antibiotic (phosphonic acid derivative). It inhibits the synthesis of the bacterial cell wall, blocking one of the first stages of peptidoglycan synthesis.

Pharmacodynamics.

Urofoscin 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. Therefore, it inactivates the enzyme enolpyruvyl transferase, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with phosphoenolpyruvate, one of the first steps in the synthesis of the bacterial cell wall. Fosfomycin can also reduce the adhesion of bacteria to the epithelium of the bladder mucosa, which can be a provoking factor in the development of recurrent infections.

The table below 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 diameter of the zone of complete inhibition >16 mm (on Mueller-Hinton medium) were classified as susceptible (corresponding to 200 μg/mL).

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 very low.

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

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 most gram-positive and gram-negative microorganisms that cause urinary tract infections, as well as penicillinase-producing strains.

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

In addition, Urofoscin reduces the adhesion of bacteria to the epithelium of the bladder mucosa, which can be a provoking 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, the time to maximum concentration (tmax) is 2–2.5 hours and the maximum concentration (Crnax) 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 approximately 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 unchanged in the urine within 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 (t1/2) is increased (up to 50 hours at a creatinine clearance of 10 ml/min).

Indication

Treatment of acute uncomplicated lower urinary tract infections caused by fosfomycin-susceptible microorganisms in men, girls aged 12 years and older and women. Prophylaxis during diagnostic procedures and surgical interventions in adult patients.

Contraindication

Hypersensitivity to the components of the drug, severe renal failure (creatinine clearance <10 ml/min), children under 12 years of age, undergoing hemodialysis.

Interaction with other medicinal products and other types of interactions

Concomitant administration with metoclopramide and other drugs that increase gastrointestinal motility reduces the absorption of Urofoscin, which leads to a decrease in the concentration of Urofoscin in blood serum and urine.

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 to 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 Urofoscin in children. Since the 3 g dosage is not intended for children under 12 years of age, the drug 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 these reactions develop, fosfomycin should be discontinued and re-administration of fosfomycin to these patients is unacceptable. Adequate therapeutic measures should be taken.

Simultaneous food intake slows down the absorption of fosfomycin. Therefore, it is advisable to use the drug on an empty stomach or 2-3 hours after eating.

The use of antibiotics, including fosfomycin trometamol, can lead to the occurrence of antibiotic-associated diarrhea. The severity can vary from mild diarrhea to colitis with fatal outcome. The occurrence of severe, persistent and/or bloody diarrhea during or after (including several weeks) the end of antibiotic treatment may be a symptom of Clostridium difficile-associated diarrhea (CDAD). 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 this case, 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.

Urofoscin contains sucrose. Diabetics and those who need to follow a diet should take into account that 1 packet of Urofoscin contains 2.213 g of sucrose. Urofoscin should not be used in patients with fructose intolerance, glucose-galactose malabsorption 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.

Breastfeeding period

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

Ability to influence reaction speed when driving vehicles or other mechanisms

Urofoscin may cause dizziness, which may affect the ability to drive or operate machinery.

Method of administration and doses

Urofoscin is taken orally on an empty stomach, preferably before bedtime, after emptying the bladder. The contents of the packet are dissolved in 1 glass of water and the prepared solution is drunk immediately.

Simultaneous food intake slows down the absorption of fosfomycin. Therefore, it is advisable to use the drug on an empty stomach or 2–3 hours after a meal.

Treatment Adults and adolescents with a body weight of 50 kg or more – 1 packet of Urofoscin 3 g once a day. Prevention

Adults with a body weight of 50 kg or more – 1 packet of Urofoscin 3 g 3 hours before and 24 hours after the intervention.

Children

Possible use for the treatment of acute uncomplicated lower urinary tract infections in girls aged 12 years and older.

There is insufficient data on the therapeutic use of the drug in boys aged 12 years and older, nor is there sufficient data on the prophylactic use of the drug in both boys and girls.

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.

Side effects

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

The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 - <1/10); uncommon (≥1/1000 - <1/100); rare (≥1/10000 - <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Reporting of adverse reactions

Reporting of suspected adverse reactions after the authorisation of a medicinal product is important. It allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.

Expiration date

1.5 years.

Storage conditions

Store in original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Packaging

8 g in sachets. 1 sachet in a cardboard box.

Vacation category

According to the recipe.

Producer

PJSC "Kyivmedpreparat".

Address

Ukraine, 01032, Kyiv, Saksaganskoho St., 139.