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-6-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. andMycobacterium 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:

15 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:

Infectious-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 fosfomycin.

Carefully:

Allergic reactions to drugs in history; severe liver disease; heart and kidney failure; in elderly patients; with 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 specialist.

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

Dosing and Administration:

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

In children, beginning with the period of the newborn ™, Urophosfabol® is administered at a 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.

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

Clearance

creatinine

40-20 ml / min

20-10 ml / min

<10 ml / min

Dose / regimen

2-4 g every 12 hours

2-4 g every 24 hours

2-4 g every 48 hours

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

Method of preparation of solutions and introduction

- for direct intravenous injection of 2 g Urophosfabol® dissolve in 20 ml of water for injection (10 ml of solvent per 1 g of Urophosfabol®); Administer slowly for 5 minutes (the recommended dosing regimen is 2 g every 6-8 hours);for rapid IV infusion 4 g Urophosfabol® dissolve in 20 ml of water for injection; the resulting solution is added to 100-200 ml of compatible inf.theenvironment; Administer within 4-1 hours (the recommended dosing regimen is 4 g every 6-8 hours);
for long-term drip administration 4 g (in some clinical cases - 8 g) Urophosfabol® dissolve in 20 ml of water for injection; The resulting solution is added to 200-500 ml of a compatible infusion fluid and administered for 1 -3 hours (recommended mode is 4 g every 6-8 hours).

When dissolving Urophosfabol®, an exothermic reaction is possible.

Compatible perfusion fluids:

0.9% solution of sodium chloride (saline)
5% glucose solution
Ringer's solution
Ringer's solution with lactate

Side effects:

For phosphomycin, a minimum toxicity is characteristic; therapy is usually well tolerated, undesirable drug reactions are rare.

Allergic reactions: urticaria, chills or fever, rash, itching, cough, bronchospasm, very rarely - anaphylactic shock (<1%).

From the liver and biliary tract: a violation of liver function in the form of a progressive increase in the activity of alanine aminotransferase, aspartame aminotransferase, alkaline phosphatase, lactate dehydrogenase and serum bilirubin concentration, very rarely jaundice.

From the digestive system: diarrhea, rarely - stomatitis, nausea, vomiting, abdominal pain, anorexia.

On the part of the blood system: granulocytopenia, eosinophilia, leukopenia, very rarely - anemia, thrombocytopenia, pancytopenia and agranulocytosis (<1%).

From the side of the urinary system, rarely - renal dysfunction, increased urea concentration in the blood, proteinuria, imbalance of electrolytes (sodium and potassium).

From the nervous system: dizziness, very rarely - convulsions (when administered in high doses).

Local Reactions: tenderness along the vein into which the injections are made, rarely - phlebitis.

Other: rarely - headache, thirst, fever, malaise, peripheral edema, a feeling of discomfort in the chest, a feeling of squeezing in the chest, heart palpitations

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 bylimeeastcentth pathogens (methicillin-resistant staphylococci, enterococci, Pseudomonas aeruginosa and etc.).

In solutions it is compatible with penicillin, carbenicillin, chloramphenicol and streptomycin. In view of the possible pharmaceutical incompatibility, do not mix 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 should be taken when choosing a dose when administering the drug to elderly patients who need to reduce sodium intake due to cardiac or renal insufficiency, hypertension, etc.

Care must be taken when choosing a dose in elderly patients, because they usually have a reduced kidney function.

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; high doses of Urophosfabol® are recommended to be administered intravenously drip whenever possible.

Other precautions.

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

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.

Form release / dosage:

Powder for the preparation of a solution for intravenous administration of 1.0 g and 4.0 g

Packaging:

1 g or 4 g of active substance into glass bottles with a capacity of 10 ml and 20 ml respectively.

1 bottle of the drug, together with the instruction for use, is placed in the

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:

4 years. Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003299 / 01

Date of registration:06.03.2009

The owner of the registration certificate:ABOLMED, LLC ABOLMED, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp29.10.2015

Illustrated instructions

Instructions

Urophosfabol® (Urofosfabol)