Uronormin-F powder for preparation of oral solution 3g sachets 8g, 2pcs

Composition

Active ingredient: Fosfomycin trometamol – 5,631 g in terms of fosfomycin-3,0 Gspomogatelnye substances: Sucrose-2,213 gAromatizator tangerine-0,070 gAromatizator orange-0,070 g Sodium saccharinate-0,016 g Mass of the package contents – 8,000 g

Pharmacological action

URONORMIN-F contains fosfomycin [mono (2-ammonium-2-hydroxymethyl-1,3-propanediol) (2R-cis)-(3-methyloxyranyl) phosphonate], a broad-spectrum antibacterial agent derived from phosphonic acid intended for the treatment of urinary tract infections.

The mechanism of action is associated with the suppression of the first stage of bacterial cell wall synthesis. Being a structural analog of phosphoenolpyruvate, it competitively and irreversibly inhibits the enzyme UDP-N-acetylglucosamienolpyruvyltransferase, which catalyzes the formation of UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine from phosphoenolpyruvate and UDP-N-acetyl-D-glucosamine. The drug is also able to reduce the adhesion of bacteria to the mucous membranes of the bladder, which can 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 strengthening of the action with antibiotics of other classes, for example, with beta-lactam antibiotics.

Fosfomycin is active against a wide range of gram-positive and gram-negative microorganisms commonly isolated from urinary tract infections, such as Escherichiacoli, Citrobacterspp., Klebsiellaspp., Proteusspp., Serratiaspp., Pseudomonasaeruginosa, Enterrococcus Faecalis.

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

Pharmacokinetics:  

Suction:

 When taken orally, fosfomycin is well absorbed from the intestine and reaches a bioavailability of about 50%. The maximum plasma concentration is observed 2-2.5 hours after oral use and is 22-32 mg/l. The plasma elimination half-life is 4 hours. Ingestion slows down absorption without affecting the concentration in the urine.

Distribution:

Fosfomycin is distributed in the kidneys, bladder walls, prostate, and seminal glands. A constant concentration of fosfomycin in the urine, exceeding the Minimum Bacteriostatic Concentration (MBsC), is reached 24-48 hours after oral use. Fosfomycin does not bind to plasma proteins and crosses the placental barrier. After a single use, fosfomycin is excreted in breast milk in small amounts.

Deduction:

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

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

Indications

Treatment of infectious and inflammatory diseases (caused by microorganisms sensitive to the drug) of the lower urinary tract, including acute bacterial cystitis, exacerbation of chronic recurrent bacterial cystitis, acute bacterial vesical syndrome, bacterial nonspecific urethritis, asymptomatic massive bacteriuria (during pregnancy), postoperative urinary tract infection. Prevention of urinary tract infection during surgical procedures and transurethral diagnostic examinations.

Use during pregnancy and lactation

During pregnancy, the drug is prescribed only when the potential benefit to the mother exceeds the potential risk to the fetus. Data from a limited number of pregnancies studied show no adverse effects on pregnancy, the fetus, or the health of the newborn. If it is necessary to prescribe the drug during breastfeeding, stop breastfeeding for the duration of treatment.

Contraindications

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

Side effects

The most common adverse reactions to a single dose of fosfomycin are gastrointestinal disorders, most often diarrhea. These reactions are short-lived and occur spontaneously.

The following are adverse side effects that have been reported with fosfomycin, in clinical trials, or in post-marketing surveillance.

The frequency of reactions is indicated as follows: very common (≥ 1/10); common (≥ 1/100 – < 1/10); infrequent (≥ 1/1 000 – < 1/100); rare (≥ 1/10 000 – < 1/1 000); very rare (

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

Infectious and parasitic diseases: Infrequently: Vulvovaginitred: superinfection

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

Nervous system disorders: Infrequent: headache, dizzyingco: paresthesia

Cardiac disorders: Very rare: tachycardia

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

Disorders of the gastrointestinal tract: Infrequently: diarrhea, nausea, dyspepsia Rare: abdominal pain, vomiting Unknown: antibiotic-associated colitis, decreased appetite

Skin and subcutaneous tissue disorders: Rare: rash, urticaria, pruritismnotable: angioedema

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

Vascular disorders: Unknown: reduced blood pressure, petechiae

Liver and biliary tract disorders: Unknown: short-term increase in the activity of alkaline phosphatase and “hepatic” transaminases

Disorders of the blood and lymphatic system: Rare: aplastic anaemiareferences: eosinophilia, thrombocytosis (petechiae).

Interaction

When combined with fosfomycin, metoclopramide reduces the concentration of fosfomycin in the blood serum and urine.

Concomitant use of antacids or calcium salts leads to a decrease in the concentration of fosfomycin in blood plasma and urine. Drugs that increase the motor activity (motility) of the gastrointestinal tract can cause a similar effect (a decrease in the concentration of fosfomycin in blood plasma and urine).

There may be specific problems associated with changing the international normalized ratio (INR). Numerous cases of increased activity of antivitamin K antagonists have been reported in patients receiving antibiotics.

If there are risk factors such as severe infection, inflammation, age, or poor overall health, the change in INR may be due to both the infectious disease and its treatment. Such changes are considered more characteristic of the following classes of antibiotics: fluoroquinolones, macrolides, cyclins, cotrimoxazole, and some cephalosporins.

How to take, course of use and dosage

Inside.

The powder is dissolved in 1/2 cup of water (50-75 ml) or another drink, mixed until completely dissolved, taken immediately after dissolution. Uronormin-F is used once a day orally on an empty stomach 1 hour before or 2-3 hours after a meal, preferably before bedtime, after emptying the bladder.

Adults and children from 12 to 18 years: 1 pack (3 g) 1 time a day once. In order to prevent urinary tract infection during surgery, transurethral diagnostic procedures, fosfomycin is taken 2 times 3 g: 3 hours before the intervention and 24 hours after the intervention.

Children from 5 to 12 years: 1 packet (2 g) 1 time a day once. In order to prevent urinary tract infection during surgery, transurethral diagnostic procedures, fosfomycin is taken 2 times 2 g: 3 hours before the intervention and 24 hours after the intervention.

In more severe cases (elderly patients, recurrent infections), take another 1 packet after 24 hours.

No dose adjustment is required in patients with mild to moderate renal insufficiency.

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

Overdose

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

Special instructions

Hypersensitivity reactions, including anaphylaxis and life-threatening anaphylactic shock, may occur during treatment with fosfomycin. In such cases, it is necessary to exclude repeated use of fosfomycin and conduct adequate treatment.

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

Diarrhoea, especially severe, persistent and / or mixed with blood, observed during or after treatment with fosfomycin (including for several weeks after treatment), may be a symptom of pseudomembranous colitis caused by Clostridium difficile.

If pseudomembranous colitis is suspected or confirmed, treatment should be initiated immediately. Drugs that suppress intestinal motility are contraindicated in this clinical situation.

Use in renal insufficiency: the concentration of fosfomycin in the urine persists for 48 hours after the usual dose, if the creatinine clearance is higher than 10 ml / min. The drug is contraindicated in patients undergoing hemodialysis.

Patients with diabetes should take into account that in 1 package of the drug with a dosage of 2 g or 3 g of fosfomycin contains 2,100 g or 2,213 g of sucrose, respectively.

Patients with rare hereditary problems such as fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency should not take this medicine.

Effects on the ability to drive vehicles and mechanisms Patients should be warned about the possibility of developing dizziness, and if dizziness occurs, they should refrain from performing these activities.

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Active ingredient

Fosfomycin

Conditions of release from pharmacies

By prescription

Dosage form

solution for oral use

Purpose

Pregnant women as prescribed by a doctor, Adults as prescribed by a doctor, Children as prescribed by a doctor, Children over 12 years of age

Indications

Urethritis, Urinary Tract Infections