Phosphocin granules for oral solution sachet 3 g No. 2

Instructions for use Phosphocin granules for oral solution sachet 3 g No. 2

Composition

active ingredient: fosfomycin;

1 sachet contains: fosfomycin (in the form of fosfomycin trometamol) - 3 g;

excipients: sucrose, sodium saccharin, tangerine and orange flavors.

Dosage form

Granules for oral solution.

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

Pharmacotherapeutic group

Antimicrobial agents for systemic use.

Other antimicrobial agents. Fosfomycin. ATX code J01X X01.

Pharmacological properties

Pharmacodynamics

Fosfocin 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.

Fosfocin 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 stages of bacterial cell wall synthesis. Fosfomycin may also reduce bacterial adhesion to the epithelium of the bladder mucosa, which may 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 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. 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, Phosphocin 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

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) can be maintained for up to 48 hours after administration. 40–50% of the dose is excreted in the urine during the first 48 hours as unchanged drug.

Kinetics in special patient groups

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 lower urinary tract infections caused by organisms susceptible to fosfomycin in males and females aged 12 years and older and adult 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

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

When the drug is taken with food, fosfomycin levels in blood plasma and urine decrease, so it is recommended to take Fosfomycin 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 such 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 with adults.

Application features

There is insufficient evidence of the effectiveness of Fosfocin in children, as the 3 g dosage is not intended for children under 12 years of age, therefore Fosfocin 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 develop, the use of fosfomycin should be discontinued, and re-administration of fosfomycin in such patients is unacceptable. They should be given adequate medical measures.

The use of antibiotics, including fosfomycin trometamol, may result in antibiotic-associated diarrhea. The severity may range from mild diarrhea to fatal colitis. The occurrence of severe, persistent, and/or bloody diarrhea during or after (even several weeks) completion of antibiotic therapy may be a symptom of Clostridium difficile-associated diarrhea (CDAD). Therefore, 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.

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

Ability to influence reaction speed when driving vehicles or other mechanisms

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

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 congenital malformations 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.

Breast-feeding

Phosphocin passes into breast milk even after a single dose, so its use should be discontinued during breastfeeding.

Method of administration and doses

Phosphocin should be taken orally on an empty stomach, preferably before bedtime, after emptying the bladder. Dissolve the contents of 1 sachet in 1 glass of water and drink 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.

The drug in this dosage (3 g) should be used as indicated in patients with a body weight of 50 kg or more.

Treatment

Adults and adolescents weighing 50 kg or more should take 1 sachet (3 g) of Phosphocin once a day.

Prevention

Adults with a body weight of 50 kg or more should take 1 sachet (3 g) of Phosphocin 3 hours before and 24 hours after the intervention.

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.

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 include gastrointestinal disturbances, mainly diarrhea. These phenomena are most often short-lived and resolve on their own.

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

The frequency of side effects is determined as follows:

very common (≥ 1/10); common (≥ 1/100 - <1/10); uncommon (≥ 1/1000 - <1/100); rare (≥ 1/100 - <1/1000); very rare (<1/10000); unknown (cannot be estimated from the available data).

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

Adverse reactions and their frequency of development

Reporting of adverse reactions

It is important to report adverse reactions after the registration of medicinal products. This allows for continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any adverse reactions through the national reporting system.

Expiration date

3 years.

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

Storage conditions

Does not require any special storage conditions. Keep out of the reach of children.

Packaging

Granules for oral solution, 3 g per sachet, 2 sachets per cardboard box.

Vacation category

According to the recipe.

Producer

Labiana Pharmaceuticals, S.L.U.

Location of the manufacturer and its business address

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