Urophosfabol - instructions for use, dose, side effects, contraindications

The bactericidal action of phosphomycin is based on a violation (in the early stages) of the synthesis of peptidoglycan of the bacterial cell wall. Penetrating into a microbial cell by transport systems D-glucose-b-phosphate, the preparation irreversibly inhibits the enzyme uridine triphosphate-N-Acetylglucosaminenol pyruvyl transferase, which catalyzes the formation of uridine triphosphate-N-acetyl-3-O- (1 -carboxvinyl) -D-Glucosamine from phosphoenolpyruvate and uridin triphosphate-N-acetyl-D- glucosamine.

Fosfomycin is active (as in vitro, and in the conditions of clinical practice in the treatment of a number of infections) against gram-positive aerobes - Staphylococcus aureus, Staphylococcus epidermidis (including strains resistant to methicillin), Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Gram-negative aerobes - Escherichia coli, Citrobacter spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Providencia (Proteus) rettgeri, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa, Neisseria meningitidis, Neisseria gonorrhoeae, Salmonella spp., Shigella spp, Campylobacter spp, and Yersinia enterocolitica. Most strains Klebsiella spp and Providencia spp. moderately sensitive to the drug.

Stable Bacteroides spp., Brucella spp., Corynebacterium spp., Mycoplasma spp., Chlamydia spp., Treponema spp., Borrelia spp. and Mycobacterium spp.

The secondary resistance of microorganisms to phosphomycin is rare. A valuable property of the drug is the lack of cross-resistance with other antibacterial agents. When combined with beta-lactams, fluoroquinolones, glycopeptides or aminoglycosides, a marked synergism of the antimicrobial effect is observed with respect to a wide range of Gram-positive and Gram-negative aerobic bacteria.

Pharmacokinetics:H15 minutes after intravenous (iv) administration of 1 g of phosphomycin, the concentration of antibiotic in serum is 46 mg / l; in an hour it is reduced by half.With a slow (within 30-40 minutes) IV infusion of large doses of the drug (4 g every 6 hours), maximum concentrations of at least 250 mg / l; in the intervals between administrations, the phosphomycin content in the plasma does not drop below 20 mg / l. In children with a slow (within 60 min) IV infusion at the rate of 25 mg / kg and 50 mg / kg, after 30 minutes the serum concentrations are 55.5 mg / l and 118.8 mg / l; in an hour - 34.2 mg / l and 89.7 mg / l, respectively.

The degree of binding of phosphomycin to plasma proteins is low - 1% of the administered dose.

Due to its low molecular weight, phosphomycin well distributed in many organs and tissues of the body. Bactericidal concentrations are determined in lung tissue, pleural fluid, peritoneal fluid, bile, subcutaneous fat, muscles, bones, synovial fluid, eye tissues, endocardial valvular valves; quickly penetrates the blood-brain barrier. The concentration of the drug in the cerebrospinal fluid increases significantly with inflammation of the meninges. Penetrates and accumulates in phagocytes (neutrophils and macrophages). Penetrates through the placenta. In small concentrations penetrates into breast milk.

The half-life (T1 / 2) is, on average, 1.5-2 hours in adults and 0.69 to 1.04 hours, depending on the dose, in children. The main pathway of excretion of phosphomycin is renal (90-100% of the administered dose during the day). The drug is excreted by the kidneys unchanged, with high concentrations of antibiotic in the urine. A small part of the administered dose is excreted by the intestine, however, this way of elimination does not have a significant significance. Phosphomycin can be easily removed from the plasma during hemodialysis.

Indications:ANDInfectious-inflammatory diseases caused by drug-susceptible pathogens:

infections of soft tissues, including in patients with impaired peripheral circulation (diabetes mellitus, arterial diseases of the lower extremities), infections of burn wounds;
infection of bones and joints;
infections of the lower respiratory tract, including pneumonia and infections in patients with cystic fibrosis;
intra-abdominal infections: acute cholecystitis, cholangitis, peritonitis;
infectious and inflammatory diseases of the pelvic organs: salpingitis, endometritis, pelvicperitonitis;
urinary tract infection, including acute and exacerbation of chronic pyelonephritis.

In the following diseases, the use of combinations of Urophosfabol® with antibiotics of other groups is recommended:

infections of the central nervous system: bacterial meningitis, including postoperative;
bacterial endocarditis;
sepsis.

Contraindications:

Individual hypersensitivity to phosphomycin, succinic acid.

Carefully:

Allergic reactions to drugs in history; heart and kidney failure; elderly age (when administered in large doses); arterial hypertension.

Pregnancy and lactation:

The use of Urophosfabol® in pregnant women is possible in cases where the intended benefit to the mother exceeds the potential risk to the fetus, and should be carried out under the supervision of a doctor.

Phosphomycin in very small concentrations penetrates into breast milk. When prescribing Urophosfabol® during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenously.

Adults:

- The average single dose of Urophosfabol® is 2-4 g, which is administered every 6-8 hours.

In patients with renal insufficiency and patients on hemodialysis,a correction of the regimens of administration of Urophosphabol® is required (see table):

Clearance creatinine	40-20 ml / min	20-10 ml / min	<10 ml / min
Clearance creatinine
Dose / regimen	2-4 g every 12 hours	2-4 g every 24 hours	2-4 g every 48
		hours	hours

Patients on hemodialysis are given 2-4 g after each dialysis procedure.

For children:

- Beginning with the period of newborns, enter at the rate of 200-400 mg / kg of body weight per day. The daily dose is divided into 3 injections; intervals between administrations are 8 hours. The duration of the course of treatment with Urofosfabol® and the dosing regimen are set individually, depending on the localization of the process and the severity of the disease.

Method of preparation of solutions and introduction

for direct intravenous injection, 2 g of the drug dissolve in 20 ml of water for injection; Administer slowly for 5 minutes (the recommended dosing regimen is 2 g every 6-8 hours);
for rapid intravenous infusion, 4 g of the drug is pre-dissolved in water for injection (for every 2 g 10 ml of water for injection); add the resulting solution to 100-200 ml of compatible infusion medium; Enter for 0.5-1 hour (the recommended dosing regimen is 4 g every 6-8 hours);
for intravenous drip introduction 4 g (in some clinical cases - 8 g) of the drug previously dissolved in water for injection (for every 2 g 10 ml of water for injection); Add the resulting solution to 200-500 ml of compatible infusion fluid; Enter for 1 to 3 hours (recommended mode - 4 g every 6-8 hours).

When dissolving Urophosfabol®, an exothermic reaction is possible.

Compatible fluids for infusion:

0.9% solution of sodium chloride (saline),
5% dextrose solution,
Ringer's solution,
Ringer's solution of lactate,
1.4% sodium hydrogen carbonate solution

Side effects:

The following undesirable effects are presented according to the organ systems in accordance with the following gradation frequency of their occurrence: very frequent - more than 1/10 (more than 10%); frequent - more than 1/100 but less than 1/10 (more than 1%, but less than 10%); infrequent - more than 1/1000 but less than 1/100 (more than 0.1%, but less than 1%); rare - more than 1/10000 but less than 1/1000 (more than 0.01%, but less than 0.1%); very rare - less than 1/10000 (less than 0.01%); Unknown (based on available data can not be estimated):

Allergic reactions: rarely - a rash, acute hypersensitivity reactions (including anaphylactic shock).

From the skin and subcutaneous tissue: infrequent rash; the frequency is unknown - angioedema, itching, urticaria.

From the digestive system: infrequently - a change in taste, a decrease in appetite, nausea, vomiting, diarrhea.

From the liver and biliary tract: infrequently - a transient increase in the activity of liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase); frequency is not known - cholestatic hepatitis, jaundice.

From the nervous system: infrequently - headache, dizziness; very rarely - transient visual impairment; frequency unknown - increased fatigue, paresthesia, confusion, convulsions (with the rapid administration of large doses).

On the part of the respiratory system: infrequently - shortness of breath; frequency unknown - bronchospasm.

Local reactions: infrequently - thrombophlebitis.

Changes in laboratory performance: infrequently hypernatremia, hypokalemia.

On the part of the blood system: very rarely - aplastic anemia; frequency is unknown - eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, pancytopenia and agranulocytosis.

From the side of the cardiovascular system: the frequency is unknown - tachycardia.

Overdose:

There are no reports of an overdose of phosphomycin. The likely manifestations of acute overdose are symptoms of hypernatremia (weakness, neuromuscular agitation, drowsiness, confusion).

Treatment: symptomatic and supportive therapy, compensatory fluid administration and forced diuresis; in severe cases - hemodialysis.

Interaction:

In combinations with penicillins, cephalosporins, carbapenems, aminoglycosides, glycopeptides and fluoroquinolones phosphomycin shows a pronounced synergistic effect; this property of the drug is used in the treatment of severe infections, as well as infections caused by multiresistant pathogens (methicillin-resistant staphylococci, enterococci, enterobacteria, Pseudomonas aeruginosa and etc.). It is pharmaceutically compatible with penicillin, carbenicillin, chloramphenicol and streptomycin. Do not mix the solution of Urophosfabol® with solutions of other antibiotics

Special instructions:

Necessary precautions.

Because Urophosfabol® contains 14.5 mEq of sodium per gram of the drug, electrolyte disturbances are possible.Care must be taken when choosing a dose in elderly patients who need to reduce sodium intake due to cardiac or renal insufficiency, hypertension, etc.

Before the introduction of the drug Urophosfabol®, it is necessary to clarify the patient's allergic anamnesis in order to assess the risk of developing anaphylaxis.

Precautions regarding the administration of the drug.

To prevent the development of phlebitis or pain at the injection site, direct intravenous administration recommends the use of large amounts of a solvent, and the rate of administration should be as slow as possible; it is preferable to inject high doses intravenously with drip.

Other precautions.

In the case of long-term treatment with this drug, it is recommended to periodically monitor liver and kidney function (including blood biochemical analysis: electrolyte content, urea nitrogen, bilirubin, hepatic enzyme activity), as well as general blood test.

Effect on the ability to drive transp. cf. and fur:

There are no data indicating a negative effect of phosphomycin on the ability to drive vehicles and to engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. However, patients experiencing dizziness should refrain from driving vehicles and working with potentially dangerous mechanisms.

Form release / dosage:

Powder for solution for intravenous injection, 2.0 g.

Packaging:By 2.0 g of active substance into glass bottles with a capacity of 20 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps or crimped caps combined (aluminum with safety plastic caps).

1 The vial of the preparation together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 of the year. Do not use after the expiration date stated on the package

Terms of leave from pharmacies:On prescription

Registration number:LS-002661

Date of registration:29.03.2012

The owner of the registration certificate:PREBAND PFC, LLCPREBAND PFC, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp29.10.2015

Illustrated instructions

Instructions

Urophosfabol® (Urofosfabol)