Uronormin-F, 2 g 6 g

URONORMIN-F contains phosphomycin [mono (2-ammonium-2-hydroxymethyl-1,3-propanediol)(2R-cis)-(3-methyloxyranil) phosphonate] – a broad spectrum antibacterial agent, a phosphonic acid derivative designed to treat urinary tract infections.

The mechanism of action is associated with inhibition of the first stage of synthesis of the bacterial cell wall. Being a structural analogue of phosphoenolpyruvate it competitively inhibits irreversibly the enzyme UDF-N-acetylglucosamienolpyruviltransferase which catalyzes the reaction of formation of UDF-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine from phosphoenolpyruvate and UDF-N-acetyl-D-glucosamine. The drug is also able to reduce bacterial adhesion to the bladder mucosa, which may play the role of a predisposing factor for recurrent infections.

The mechanism of action of the drug explains the absence of cross-resistance with other classes of antibiotics and the mutual reinforcement of action with antibiotics of other classes, such as beta-lactam antibiotics.

Phosphomycin is active against a wide range of Gram-positive and Gram-negative microorganisms commonly isolated in urinary tract infections, such as Escherichia coli, Citrobacterspp., Klebsiellaspp., Proteusspp., Serratiaspp., Pseudomonasaeruginosa, Enterrococcusfaecalis.

The emergence of resistance in the laboratory is explained by mutations in the glpT and uhp genes, which control L-alpha-glycerophosphate and glucose phosphate transport, respectively.

Pharmacokinetics:

Intake:

In oral administration phosphomycin is well absorbed from the intestine and achieves bioavailability of about 50%. Maximal concentration in plasma is observed 2-2.5 hours after oral administration and is 22-32 mg/l. The plasma elimination half-life is 4 hours. Intake with food slows absorption without affecting the concentration in the urine.

Distribution:

Phosphomycin is distributed in the kidneys, bladder wall, prostate and seminal glands. A steady urinary concentration of fosfomycin exceeding the Minimum Bacteriostatic Concentration (MBc) is reached 24-48 hours after oral administration. Fosfomycin does not bind to plasma proteins and crosses the placental barrier. After a single administration, fosfomycin is excreted into breast milk in small amounts.

Fosfomycin is excreted unchanged, mainly by the kidneys, through glomerular filtration (40-50 % of the dose taken is found in the urine), with a half-life of about 4 hours, and, to a lesser extent, with the feces (18-28 % of the dose). The occurrence of a second peak serum concentration 6 and 10 hours after drug administration suggests that the drug is subject to intestinal hepatic recirculation.

Pharmacokinetic properties of fosfomycin are independent of age and pregnancy. The drug cumulates in patients with renal insufficiency; a linear relationship between pharmacokinetic parameters of fosfomycin and glomerular filtration rate has been established.

Indications

Urinary tract infections, PainThe treatment of infectious and inflammatory diseases (caused by drug-sensitive microorganisms) of the lower urinary tract, including Acute bacterial cystitis, exacerbation of chronic recurrent bacterial cystitis, acute bacterial urovesical syndrome, bacterial nonspecific urethritis, asymptomatic massive bacteriuria (in pregnancy), postoperative urinary tract infection.

Prevention of urinary tract infection during surgical interventions and transurethral diagnostic examinations.

Active ingredient

Fosfomycin

Composition

1 package contains:
Active ingredient:
Fosfomycin trometamol – 3.754 g
in terms of fosfomycin – 2.0 g
Excipients:
Saccharose -2,100 g
Mandarin flavoring – 0,070 g
Orange flavoring – 0,060 g
Sodium saccharinate -0,016 g
Package contents weight 6,000 g

How to take, the dosage

Inside.

The powder is dissolved in 1/2 cup of water (50-75 ml) or other beverage, stirred until completely dissolved, taken immediately after dissolution. Uronormin-F is taken once a day orally on an empty stomach 1 hour before or 2-3 hours after a meal, preferably before going to bed, after first emptying the bladder.

Adults and children 12-18 years old take 1 sachet (3 g) once a day.
In order to prevent urinary tract infection during surgical and transurethral diagnostic procedures fosfomycin is taken twice in 3 g: 3 hours before and 24 hours after the intervention.

In children from 5 to 12 years of age: 1 sachet (2 g) once a day. For prevention of urinary tract infection during surgical interventions and transurethral diagnostic procedures fosfomycin is taken 2 g 2 times: 3 hours before the intervention and 24 hours after the intervention.

In more severe cases (elderly patients, recurrent infections), another 1 bag is taken 24 hours later.

In patients with mild to moderate renal insufficiency, no dose adjustment is required.

In patients with severe renal failure or those undergoing hemodialysis, use of the drug is contraindicated. No dose adjustment is required in patients with hepatic impairment.

Interaction

When concomitant use with fosfomycin, metoclopramide reduces the concentration of fosfomycin in serum and urine.

Simultaneous use of antacids or calcium salts leads to decreased concentration of phosphomycin in plasma and urine. Drugs that increase motor activity (motility) of the gastrointestinal tract may cause a similar effect (decrease in plasma and urinary concentrations of phosphomycin).

Possible specific problems associated with changes in the international normalized ratio (INR). Numerous cases of increased antivitamin K antagonist activity have been reported in patients receiving antibiotics.

In the presence of risk factors such as severe infection, inflammation, age or poor general health, changes in INR may be due to either an infectious disease or a consequence of its treatment. Such changes are considered more common with the following classes of antibiotics: fluoroquinolones, macrolides, cyclines, cotrimoxazole and some cephalosporins.

Special Instructions

During treatment with fosfomycin hypersensitivity reactions may occur, including anaphylaxis and anaphylactic shock, which are life-threatening. In such cases it is necessary to exclude repeated administration of fosfomycin and conduct adequate treatment.

The use of almost all antibacterial agents, including fosfomycin, may lead to antibiotic-associated diarrhea. Its severity can range from mild diarrhea to fatal colitis.

Diarrhea, particularly severe, persistent and/or bloody diarrhea seen during or after treatment with phosphomycin (including for several weeks after treatment), may be a symptom of pseudomembranous colitis caused by Clostridium difficile.

If the diagnosis of pseudomembranous colitis is suspected or confirmed, treatment should be started immediately. Drugs that inhibit intestinal peristalsis are contraindicated in this clinical situation.

Application in renal failure: Fosfomycin concentration in urine is maintained for 48 hours after the usual dose, if creatinine clearance is higher than 10 ml/min. The drug is contraindicated in patients undergoing hemodialysis.

Patients with diabetes mellitus should note that 1 bag of the drug with a dosage of 2 g or 3 g of phosphomycin contains 2.100 g or 2.213 g of sucrose, respectively.

Patients with rare hereditary diseases, such as fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency are contraindicated with this drug.

Influence on the ability to drive vehicles, mechanisms

Patients should be warned about the possibility of developing dizziness, and in case of dizziness should refrain from performing the specified activities.

Contraindications

– Hypersensitivity to phosphomycin and other components of the drug;
– severe renal insufficiency (creatinine clearance <10 ml/min);
– Children under 5 years of age (for the dosage of 2 g), children under 12 years of age (for the dosage of 3 g);
– hemodialysis;
– sugar/isomaltase deficiency;
– fructose intolerance;
– glucose-galactose malabsorption.

Side effects

The most common adverse reactions to a single dose of fosfomycin are gastrointestinal disorders, most commonly diarrhea. These reactions are transient and go away spontaneously.

The following are adverse adverse reactions that have been reported with fosfomycin in clinical trials or post-registration surveillance.

The frequency of reactions is listed as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); infrequent (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); unknown – the frequency of adverse reactions cannot be estimated from available data.

In each group, adverse reactions are presented in descending order of severity.

Infectious and parasitic diseases:
Infrequent: vulvovaginitis
Rarely: superinfection

Immune system disorders:
Unknown: Anaphylactic reactions, including anaphylactic shock, hypersensitivity

Nervous system disorders:
Infrequent: headache, dizziness
Rarely: paresthesias

Heart disorders:
Very rare: tachycardia

Respiratory system, thoracic and mediastinal organs disorders:
Unknown: asthma, bronchospasm, shortness of breath

Gastrointestinal tract disorders:
Infrequent: diarrhea, nausea, dyspepsia
Rarely: Abdominal pain, vomiting
Unknown: antibiotic-associated colitis, decreased appetite

Skin and subcutaneous tissue disorders:
Rare: rash, urticaria, itching
Unknown: Angioneurotic edema

General disorders and disorders at the injection site:
Rarely: fatigue

Vascular disorders:
Unknown: decreased blood pressure, petechiae

Hepatic and biliary tract disorders:
Unknown: transient increase in the activity of alkaline phosphatase and “hepatic” transaminases

Blood and lymphatic system disorders:
Rarely: aplastic anemia
Unknown: eosinophilia, thrombocytosis (petechiae).

Overdose

There are limited data regarding oral overdose of fosfomycin. In patients who took an excessive dose of the drug the following reactions were observed: vestibular dysfunction, hearing disorders, “metallic” taste in the mouth, as well as a general decrease in taste perception.
Treatment in overdose is symptomatic and supportive.
In case of overdose fluid intake to increase diuresis is recommended.

Pregnancy use

In pregnancy, the drug is prescribed only when the potential benefit to the mother outweighs the potential risk to the fetus. Data from a limited number of pregnancies studied show no adverse effects on pregnancy, fetus or the health of the newborn.

If it is necessary to prescribe the drug during breastfeeding, breastfeeding should be stopped for the duration of treatment.

Similarities

Monural, Ecofomural, Fosfomycin, Uronormin-F