Phosphococci granules for oral solution 3 g sachet No. 1

Instructions for Phosphococ 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: sucrose, sodium saccharin, tangerine flavor, orange flavor.

Dosage form

Granules for oral solution.

Main physicochemical properties: white or almost white granules without lumps or particles.

Pharmacotherapeutic group

Antimicrobials for systemic use. Other antimicrobials. Fosfomycin. ATX code J01X X01.

Pharmacological properties

The drug 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.

The drug 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 can also reduce bacterial adhesion 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 zone of complete inhibition > 16 mm in diameter (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 a few bacteria can acquire 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 ESBL (extended-spectrum beta-lactamases), are susceptible to fosfomycin. Similarly, most types of methicillin-resistant Staphylococcus aureus are 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, the drug 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, tmax is 2–2.5 hours and 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 enters 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 during the first 48 hours in unchanged form.

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

Treatment of acute uncomplicated cystitis in women and girls aged 12 years and older. 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 the 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 motility reduces the absorption of fosfomycin, which leads to a decrease in the concentration of the drug in blood serum and urine.

When the drug is taken with food, fosfomycin levels in blood plasma and urine 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. There have been numerous reports of increased antivitamin K antagonist activity 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 due 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 have only been conducted in adult patients.

Application features

Hypersensitivity reactions.

Serious and sometimes fatal hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during treatment with fosfomycin (see sections 4.3 and 4.8). If such reactions occur, fosfomycin treatment should be discontinued immediately and appropriate emergency measures should be taken. Clostridioides difficile-associated diarrhoea.

Clostridioides difficile-associated colitis and pseudomembranous colitis have been reported with fosfomycin, and the severity of these cases can range from mild to life-threatening (see section 4.4). Therefore, it is important to consider this diagnosis in patients who develop diarrhoea during or after fosfomycin treatment. Discontinuation of fosfomycin and specific treatment for Clostridioides difficile should be considered. Medicinal products that inhibit peristalsis should not be used. Paediatric patients.

The safety and efficacy of fosfomycin in children under 12 years of age have not been established. Therefore, this medicinal product should not be used in this age group (see section 4.2).

Persistent infections and male patients.

In case of persistent infections, careful investigation and re-evaluation of the diagnosis is recommended, as this is often associated with complicated 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).

Kidney failure.

Fosfomycin urinary concentrations remain therapeutically effective for 48 hours if creatinine clearance is above 10 ml/min.

Important information about excipients.

The medicine contains sucrose. Patients with diabetes mellitus and those who must follow a diet should take into account that 1 sachet of the medicine contains 2.213 g of sucrose. The medicine FOSFOCOC should not be used in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrose-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 harmful effects with respect to pregnancy, embryonic, fetal 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 outweighs the potential risk to the fetus. Breastfeeding

Fosfomycin passes into 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

Fosfomycin may cause dizziness, which may affect the 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 should be 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 should be given 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.

Use in girls aged 12 years and older for the treatment of 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 by oral administration are limited. Symptoms.

Vestibular disorders, hearing impairment, 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. In case of overdose, the patient should be monitored (especially plasma/serum electrolyte levels). It is recommended to drink plenty of fluids to increase diuresis. Fosfomycin is effectively removed from the body by hemodialysis with a mean half-life of approximately 4 hours.

Adverse reactions

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

All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Reporting of suspected adverse reactions.

Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the 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 Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Expiration date

3 years.

Storage conditions

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

Packaging

8 g of granules in a sachet; 1 or 2 sachets in a cardboard pack.

Vacation category

According to the recipe.

Producer

Labiana Pharmaceuticals, SLU

Location of the manufacturer and address of its place of business

Calle Casanova, 27-31, Corbera De Llobregat, Barcelona, 08757, Spain/

C/Casanova, 27-31, Corbera de Llobregat, Barcelona, 08757, Spain.