Espa-focin®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESPA-FOCIN® (ESPA-FOCIN®)

Composition:

Active substance: fosfomycin;

1 sachet contains 5631.0 mg of fosfomycin trometamol, equivalent to 3000 mg of fosfomycin;

Excipients: sucrose.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white or almost white granular powder, free from extraneous particles.

Pharmacotherapeutic group. Antimicrobial agents for systemic use.

ATC Code J01XX01.

Pharmacological properties.

Pharmacodynamics.

Fosfomycin trometamol is a broad-spectrum antibiotic, a derivative of phosphonic acid. Its mechanism of action is related to inhibition of the first stage of bacterial cell wall synthesis. The specific mechanism of enolpyruvyl transferase inhibition prevents development of cross-resistance with other antibiotics.

It is effective against Gram-positive and Gram-negative microbial strains, including penicillinase-producing strains, and major causative agents of urinary tract infections: E. coli, Proteus, Klebsiella, Enterobacter, Staphylococcus, Streptococcus, and other resistant strains.

Pharmacokinetics.

ESPА-FOTSIN® is well absorbed in the gastrointestinal tract. Maximum plasma concentration (20–30 mcg/mL) is reached within 2–2.5 hours after administration. Therapeutic concentrations in urine are maintained for up to 48 hours.

Clinical characteristics.

Indications.

Treatment of acute uncomplicated lower urinary tract infections caused by microorganisms sensitive to fosfomycin in adult patients and in girls aged 12 years and older. Prevention of infectious diseases during diagnostic procedures and surgical interventions in adult patients.

Contraindications.

Hypersensitivity to the components of the drug, severe renal impairment (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 reduces absorption of fosfomycin, resulting in decreased fosfomycin concentrations in blood serum and urine.

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

Specific issues regarding fluctuations in INR (International Normalized Ratio). Numerous cases of increased antagonistic activity of vitamin K antagonists have been reported in patients taking antibiotics. Risk factors include: severe infections or inflammation, advanced age, and poor general health status. In such cases, it is difficult to determine whether the change in INR is related to the infectious disease itself or caused by drug intake. However, certain classes of antibiotics are more frequently associated with INR fluctuations, particularly: fluoroquinolones, macrolides, tetracyclines, co-trimoxazole, and some cephalosporins.

Interaction studies have been conducted only in adults.

Special precautions for use

There is insufficient evidence of efficacy of fosfomycin in children, as the 3 g dose is not intended for use in children under 12 years of age; therefore, the drug should not be administered to this age group.

The use of broad-spectrum antibiotics, including fosfomycin trometamol, may lead to the development of antibiotic-associated colitis (including pseudomembranous colitis). Therefore, this diagnosis should be considered in patients who develop severe diarrhea during or after treatment with fosfomycin trometamol. The severity may range from mild diarrhea to colitis with fatal outcome. The occurrence of severe, persistent and/or bloody diarrhea during or after (including several weeks after) completion of antibiotic therapy may indicate Clostridium difficile-associated diarrhea (CDAD). If this diagnosis is confirmed, appropriate treatment must be initiated immediately. In such cases, drugs that inhibit intestinal peristalsis are contraindicated.

Patients with diabetes mellitus and those requiring dietary restrictions should be aware that each sachet of ESPA-FOSIN® contains 2.369 g of sucrose. The drug should also not be administered to patients with hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Transient increases in hepatic transaminase activity are possible.

Clinical symptoms usually resolve by the 2nd or 3rd day of treatment. Occasionally, certain symptoms may persist, which do not necessarily indicate absence of therapeutic effect but may be due to inflammatory processes.

Fosfomycin may cause hypersensitivity reactions, including anaphylaxis and anaphylactic shock, which may be life-threatening (see section "Adverse reactions").

If such reactions occur, fosfomycin should be discontinued immediately, and re-administration of fosfomycin to these patients is not permitted. Appropriate therapeutic measures should be initiated.

Renal impairment: Therapeutic concentrations of fosfomycin in urine are maintained for up to 48 hours if creatinine clearance is above 10 mL/min.

Use during pregnancy or breastfeeding

Fosfomycin may be used during pregnancy only if clearly needed, when the expected benefit to the mother outweighs the potential risk to the fetus.

Available data indicate that fosfomycin trometamol has neither teratogenic nor fetotoxic effects. Reproductive toxicity was not observed in animal studies.

The drug should not be used during breastfeeding. Studies on use during breastfeeding have not been conducted.

Ability to affect reaction speed when driving or operating machinery

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

Dosage and Administration.

Take orally on an empty stomach. Dissolve the contents of the sachet in 125 ml
(1/2 glass) of cold water, stir until completely dissolved, and drink. Dosages are determined individually by a physician.

The usual single dose for adults (including elderly patients) and girls aged 12 years and older during the acute phase of illness is 3 g of fosfomycin (1 sachet) as a single dose.

For prophylaxis of urinary tract infections during surgical procedures and transurethral diagnostic procedures, administer 3 g of fosfomycin (1 sachet) 3 hours before the procedure and 3 g of fosfomycin (1 sachet) 24 hours after the procedure.

Children.

The drug may be used for the treatment of acute uncomplicated lower urinary tract infections in girls aged 12 years and older.

There is insufficient data on the use of the drug for therapeutic purposes in boys aged 12 years and older, as well as insufficient data on its use for prophylactic purposes in both boys and girls.

Overdose.

Data on fosfomycin overdose following oral administration are limited.

Symptoms: vestibular disturbances, hearing impairment, metallic taste in the mouth, and general reduction in taste perception.

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

Treatment: symptomatic and supportive therapy. Increased fluid intake is recommended to enhance diuresis.

Adverse reactions.

The most common adverse reactions associated with a single dose of fosfomycin trometamol are gastrointestinal disturbances, primarily diarrhea. These events are usually transient and resolve spontaneously.

The frequency of adverse effects 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 (<1/100000);

unknown (cannot be estimated from the available data).

Within each frequency category, adverse reactions are listed in order of decreasing frequency.

Shelf life. 2 years. The prepared solution must not be stored.

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

Packaging. 8 g of powder (3000 mg of active substance) in a sachet (paper-aluminum-polyethylene), 1 sachet in a cardboard pack.

Prescription status. Prescription only.

Manufacturer.

Lindopharm GmbH.

Manufacturer's address.

Neustrasse 82, 40721 Hilden, Germany.

Marketing Authorization Holder.

Esparma GmbH, Germany.

Address of the Marketing Authorization Holder.

Bielefelder Strasse 1, 39171 Sulzetal, Germany.