Ecofomural, 3 g

Pharmacotherapeutic group

Antibiotic

ATX code

J01XX01

Pharmacodynamics:

Ecofomural® (active ingredient: phosphomycin) is a broad-spectrum antibiotic derived from phosphonic acid.

Ecofomural® being a structural analogue of phosphoenol pyruvate inactivates the enzyme N-acetylglucosamino-3-o-enolpyruvil-transferase irreversibly blocks condensation of uridine diphosphate-N-acetylglucosamine with phosphoenol pyruvate inhibits the synthesis of UDF-N-acetylmuramic acid as a result of which the initial stage of bacterial cell wall peptidoglycan formation is suppressed and, as a consequence, microbial cell death occurs (bactericidal action). Inactivation of N-acetyl-glucosamine-3-o-enolpyruvil-transferase enzyme reduces the possibility of cross-resistance to antibiotics with a similar mechanism of action and creates conditions for synergism (in vitro experiments synergistic effect with amoxicillin cephalexin pepemidic acid was revealed).

Invitro to fosfomycin are sensitive Gram-positive (Staphylococcus saprophyticus Enterococcus faecalis) and Gram-negative (Escherichia coli Klebsiella pneumonia Citrobacler spp. Enterobacter spp. Proteus mirabilis) microorganisms.

Fosfomycin reduces adhesion of a number of bacteria on the epithelium of the urinary tract.

Pharmacokinetics:

Intake:

Phosphomycin is rapidly absorbed from the gastrointestinal tract when taken orally. In the body it dissociates into phosphomycin and trometamol. The latter has no antibacterial properties. Bioavailability of a single oral dose of 30 g is 34 to 65%. Maximum plasma concentration (Cmax) is observed 2-25 hours (Tmax) after oral administration and is 22-32 mg/l (Cmax). The plasma elimination half-life is 4 hours.

Distribution:

Phosphomycin does not bind to plasma proteins and is not metabolized in the body and accumulates in the urine. When a single dose of 30 g is taken orally, a high concentration of the antibiotic (1,053 to 4,415 mg/L) pa 99% bactericidal for most common pathogens of urinary tract infections is achieved in the urine. The minimum inhibitory concentration of phosphomycin for these pathogens is 128 mg/L and is maintained in the urine for 24-48 hours, which suggests a one-day course of treatment with a single administration of the drug.

90% of phosphomycin is excreted unchanged by the kidneys with high concentrations in the urine. About 10% of the administered dose of the drug is excreted unchanged in the intestine. In patients with moderately reduced renal function (creatinine clearance <80 ml/min) including age-related physiological reduction in renal function (elderly people) the half-life of phosphomycin is prolonged but the concentration in urine remains at therapeutic level.

Indications

Acute uncomplicated lower urinary tract infections (acute cystitis) in women 18 years and older, caused by fosfomycin-sensitive pathogens Escherichia coli, Enterococcus faecalis. Fosfomycin is not indicated for the treatment of pyelonephritis or perinephric abscess.

Active ingredient

Composition

Composition per sachet:

active ingredient: fosfomycin trometamol (in terms of 100% substance) – 5.629 g in terms of fosfomycin – 3.0 g;

excipients: lactulose – 1.500 g, sodium saccharinate – 0.016 g, strawberry flavoring – 0.070 g, maltitol – to the weight of 8.0 g.

How to take, the dosage

Ecofomural® is taken once on an empty stomach 2 to 3 hours before or after a meal, preferably before going to bed, after first emptying the bladder: adults and children over 12 years old in a daily dose of 30 g children from 5 to 12 years old in a daily dose of 20 g. The contents of the package is dissolved in ½ cup of water

The course of treatment is 1 day.

To prevent urinary tract infections during surgical interventions and diagnostic procedures, the above dose is taken twice – 3 hours before and 24 hours after the intervention.

Interaction

Metoclopramide. When concomitant use of fosfomycin and metoclopramide, which increases gastrointestinal motility, the concentration of fosfomycin in blood serum and its excretion in the urine are reduced. Other drugs that increase gastrointestinal motility may have a similar effect.

Probenecid. Probenecid should not be administered concomitantly with fosfomycin, because it has been proven to significantly reduce renal clearance and excretion of fosfomycin.

Probenecid when administered to healthy volunteers receiving fosfomycin infusion significantly decreased renal clearance, probably by inhibiting tubular secretion, resulting in lower urinary concentrations of the drug.

Therapeutic evaluation of the effects of metoclopramide and probenecid on urinary fosfomycin levels after their combined use with fosfomycin in women with acute urinary tract infection has not been performed. Based on data obtained in healthy volunteers, urinary concentrations of phosphomycin cannot exceed the bactericidal concentration for a long enough period of time to lead to a microbiological cure. None of these drugs should be administered concomitantly with fosfomycin.

Cimetidine. Cimetidine does not affect the pharmacokinetics or urinary concentrations of phosphomycin when used together.

Eating. Food intake delays the absorption of phosphomycin, which leads to a decrease in plasma Cmax and urinary concentrations. Therefore, it is recommended that fosfomycin tromethamine be taken on an empty stomach or at least 2-3 h after a meal.

Special Instructions

Ecofomural® administration with meals leads to delayed absorption; therefore, it is recommended to take the drug 2-3 hours before or after meals.

Diarrhea may occur during or after treatment with fosfomycin in which case the diagnosis of pseudomembranous colitis should be excluded and appropriate treatment should be prescribed. Administration of drugs suppressing intestinal peristalsis is contraindicated.

Patients with diabetes should note that the drug contains maltitol. Insulin is required for metabolism of maltitol but due to its slow and poor absorption from the gastrointestinal tract maltitol has little effect on glucose concentration in plasma; therefore no dose adjustment of hypoglycemic preparations is required.

Due to maltitol content, Ecofomural® is not recommended for patients with hereditary fructose intolerance.

Contraindications

Side effects

In three U.S. studies, 1,233 patients received therapy with fosfomycin. The most frequent adverse reactions that occurred in >1% of patients, regardless of association with drug use, were diarrhea (10.4%), headache (10.3%), vaginitis (7.6%), nausea (5.2%), rhinitis (4.5%) back pain (3.0%), dysmenorrhea (2.6%), pharyngitis (2.5%), dizziness (2.3%), abdominal pain (2.2%), pain (2.2%), dyspepsia (1.8%), asthenia (1.7%) and rash (1.4%).

In addition, the following adverse reactions were observed with a frequency of less than 1%: Stool disorders, anorexia, constipation, dry mouth, dysuria, hearing loss, fever, flatulence, flu-like syndrome, hematuria, infections, insomnia, lymphadenopathy, menstrual disorders, migraine, myalgia, nervousness, paresthesia, itching, skin conditions (skin disorders) and vomiting.

In the U.S. study population, statistically significant laboratory changes reported without drug association included increased eosinophil counts, increased or decreased white blood cell counts, increased bilirubin, ALT and AST levels, ALP, decreased hematocrit, Hb levels, and increased and decreased platelet counts. The changes were usually transient, clinically insignificant, and occurred in less than 1% of patients.

In the same population, there have been studies of adverse adverse reactions that were considered associated with fosfomycin administration and occurred in more than 1% of patients receiving fosfomycin. They included diarrhea (9%), vaginitis (5.5%), nausea (4.1%), headache (3.9%), dizziness (1.3%), asthenia (1.1%), and dyspepsia (1.1%). The most frequently observed reaction, diarrhea, was considered mild and transient (passed without any intervention).

One case of unilateral optic neuritis has been reported and was considered probably associated with fosfomycin use.

In the post-registration period of fosfomycin use, there have been reports of vulvovaginitis, tachycardia, hearing impairment, urticaria and anaphylactic reactions, including anaphylactic shock and hypersensitivity. Cases of angioedema, aplastic anemia, asthma (exacerbation), cholestatic jaundice, general reduction in taste sensation, hepatic necrosis, metallic taste in the mouth, and vestibular disorders have also been reported. One case of toxic megacolon has been reported and was found to be unrelated to phosphomycin administration.

Overdose

The data on fosfomycin overdose with oral administration are limited.

Symptoms: in cases of overdose during parenteral use hypotension, somnolence, disorders of water-electrolyte balance, thrombocytopenia and hypoprothrombinemia have been reported.

Treatment: in case of overdose symptomatic and supportive therapy should be carried out. Excretion of fosfomycin with urine should be stimulated by adequate fluid intake.

Pregnancy use

Similarities