UROFOSFABOL

Active material: Fosfomycin
When ATH: J01XX01
CCF: Antibiotic group of phosphonic acid derivatives
ICD-10 codes (testimony): A39, A41, G00, i33, J15, J20, J42, J85, J86, K65.0, K81.0, K83.0, L01, L02, L03, L08.0, M00, M86, N10, N11, N30, N34, N41, N70, N71, N72, N73.0, T79.3
When CSF: 06.14
Manufacturer: ABOLmed Ltd. (Russia)

Pharmaceutical form, composition and packaging

Powder for solution for i / v administration white or white with a yellowish tint.

Excipients: succinic acid (20 mg).

Glass Bottles capacity 20 ml (1) – packs cardboard.
Glass Bottles capacity 20 ml (5) – packings Valium planimetric (1) – packs cardboard.

Powder for solution for i / v administration white or white with a yellowish tint.

Excipients: succinic acid (40 mg).

Glass Bottles capacity 20 ml (1) – packs cardboard.

Powder for solution for i / v administration white or white with a yellowish tint.

Excipients: succinic acid (80 mg).

Glass Bottles capacity 60 ml (1) – packs cardboard.
Glass Bottles capacity 60 ml (5) – packings Valium planimetric (1) – packs cardboard.

Pharmacological action

Antibiotic group of phosphonic acid derivatives.

The bactericidal effect of fosfomycin is based on the disruption in the early stages of peptidoglycan synthesis of the bacterial cell wall. Penetrating into the microbial cell through the transport systems of D-glucose-6-phosphate, the drug irreversibly inhibits the enzyme uridine-diphospho-N-acetylglucosamine-3-0-enolpyruvate transferase (MurA), which is involved in the synthesis of uridine-diphospho-N-acetylmuramic acid from uridine- N-acetylglucosamine.

It is active against gram-positive aerobes: Staphylococcus aureus, Staphylococcus epidermidis (incl. some strains, resistant to metitillino), Staphylococcus spp., Streptococcus pyogenes, Streptococcus viridans, group C streptococci, F, G, Streptococcus pneumoniae, Enterococcus faecalis, Bacillus anthracis; Gram-negative aerobic: Aeromonas hydrophila, Citrobacter spp., Campylobacter jejuni, Escherichia coli, Enterobacter spp. (moderately sensitive), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca (moderately sensitive), Morganella morganii (most strains are moderately sensitive), Neisseria gonorrhoeae, Neisseria meningitidis, Proteus is wonderful, Proteus vulgaris, Rettgeri Providence (moderately sensitive), Pseudomonas aeruginosa, Serratia wilting, Salmonella spp., Shigella spp., Vibrio spp. (moderately sensitive), Yersinia enterocolitica; anaerobes: Actinomyces spp., Peptococcus spp., Peptostreptococcus spp., Fusobacterium spp., Veillonella spp.

C drug moderately sensitive Clostridium perfringens, Prevotella spp.

C drug resistant Legionella spp., Borrelia spp., Listeria monocytogenes, Mycobacterium spp., Bacteroides spp., most intracellular pathogens (Coxiella burnetii, Rickettsia spp., Chlamydia spp., Mycoplasma pneumoniae, Ureaplasma urealyticum).

Secondary resistance of microorganisms to Urofosfabol^® rarely develops. A valuable property of the drug is the absence of cross-resistance with other antibacterial agents.. Acts synergistically in combination with beta-lactam antibiotics, aminoglycosides and vancomycin.

Pharmacokinetics

Distribution

Through 15 min after intravenous administration of the drug in a dose 500 mg 1 g the concentration of fosfomycin in serum is 28 mg/l and 46 mg / l, respectively; through 1 h they are halved. When slow (during 30-40 m) infusion of large doses of the drug (4 g every 6 no) C_max is greater than 250 mg / l. In the intervals between injections, the content of fosfomycin in plasma is not less than 20 mg / l.

Plasma protein binding of fosfomycin is low – 1%.

Low molecular weight, fosfomycin is well distributed in many organs and tissues of the body. Bactericidal concentrations are determined in lung tissue, pleural fluid, perytonealnoy fluid, bile, subcutaneous fat, muscle, bones, synovial fluid, eye tissues, heart valve endocardium. Quickly penetrates the BBB. The concentration of the drug in the cerebrospinal fluid increases significantly with inflammation of the meninges. Penetrates and accumulates in phagocytic cells (neutrophils and macrophages). Passes through the placenta. In small concentrations excreted in breast milk.

Deduction

T_1/2 is, average, 1.5-2 h in adults and from 0.69 to 1.04 no, dose dependent, – children. The main route of elimination of fosfomycin – kidney (90-100% from the administered dose during the day). The active form of the drug is excreted in the urine.. A small part of the administered antibiotic is excreted in the bile, however, this elimination pathway is not essential. Fosfomycin can be easily removed from plasma by hemodialysis.

Pharmacokinetics in special clinical situations

In children with slow (during 60 m) intravenous infusion based on 25 mg / kg 50 mg / kg through 30 min serum concentrations are 55.5 mg/l and 118.8 mg / l; through 1 no – 34.2 mg/l and 89.7 mg/l, respectively.

Testimony

-CNS infections: bacterial meningitis (primary and secondary, incl. postoperative), ventriculitis;

- soft tissue infections, incl. in patients with peripheral circulatory disorders (diabetes, lower limb artery disease), burn wound infection;

- Bone and joint infections: acute and chronic hematogenous osteomyelitis in children and adults, post-traumatic and postoperative osteomyelitis, infectious arthritis;

- Infections of the lower respiratory tract: bacterial pneumonia, requiring hospital treatment, especially in cases of pneumococcal discharge, resistant to penicillin, as well as gram-negative pathogens from the Enterobacteriaceae family; pulmonary infections in patients with cystic fibrosis;

- Infections of the abdominal cavity: Acute cholecystitis, kholangit, secondary peritonitis;

- infectious and inflammatory diseases of the pelvic organs in women: salpingitis, endometritis, pelvioperitonit;

- Urinary tract infections: acute pyelonephritis with moderate and severe course, complicated and exacerbated chronic urinary tract infections (pyelonephritis against the background of urolithiasis, infectious complications of hydronephrosis, postoperative infections in urology);

- Bacterial endocarditis.

Indications for the use of combinations of Urofosfabol^® with antibiotics of other groups are severe infections, incl. mixed flora, as well as with the failure of previous therapy:

- Septicemia, caused by enterobacteria (Klebsiella spp., Proteus spp., Enterobacter spp., Mercerizing sawmills) и Pseudomonas aeruginosa – combination with cephalosporins, penicillins (active against Pseudomonas aeruginosa), aminoglycosides or fluoroquinolones;

- Bacterial meningitis – combination with cephalosporins, ampicillin or rifampicin;

— severe infections, caused by methicillin-susceptible strains of Staphylococcus aureus, Staphylococcus epidermidis или Enterococcus spp. – combinations with oxacillin or ampicillin;

- Infections, caused by methicillin-resistant strains of Staphylococcus aureus or Staphylococcus epidemidis – combinations with glycopeptides;

- intra-abdominal and pelvic infections in women – combination with antibiotics, active against anaerobes (metronidazol) or with aminoglycosides;

- infections in patients with blood diseases and neutropenia – combinations with cefoperazone / sulbactam, IV generation cephalosporins or carbapenems;

- Infections, caused by multidrug-resistant strains of Pseudomonas aeruginosa – combinations with IV generation cephalosporins, aztreonam or carbapenems.

Dosage regimen

The drug is introduced into / in.

Average dose of Urophosphabol^® in Adult is 2-4 g, which introduce every 6-8 no.

In children, from the neonatal period, Urophosphobol^® administered at the rate of 200-400 mg / kg body weight / day. The daily dose is divided into 3 introduction; the intervals between injections are 8 no.

In patients with renal insufficiency and patients, hemodialysis, correction of the modes of administration of Urofosfabol is required^®.

Patients, hemodialysis, administered by 2-4 d after each dialysis procedure.

Rules for the preparation of solutions and administration

To intravenous jet injection 2 g Urophosphabol^® dissolved in 20 ml water for injection (10 ml of solvent per 1 g product). Inject slowly over 5 m (recommended dosage regimen – 2 g every 6-8 no).

To rapid intravenous infusion 4 g Urophosphabol^® dissolved in 20 ml water for injection; the resulting solution is added to 100-250 ml compatible infusion medium. Injected within 0.5-1 no (recommended dosage regimen – 4 g every 6-8 no).

To long-term drip 4 g (in some clinical cases – 8 g) Urophosphabol^® dissolved in 20 ml water for injection. The resulting solution is added to 250-500 ml of compatible fluid for infusion and administered within 1-3 no (recommended mode – 4 g every 6-8 no).

When Urophosphabol is dissolved^® possible exothermic reaction.

Compatible infusion liquids: 0.9% sodium chloride solution (saline solution), 5% Dextrose (Glucose), Ringer, Ringer lactated.

Side effect

Fosfomycin has minimal toxicity. Therapy is usually well tolerated, adverse drug reactions are rare.

Liver and biliary tract: dysfunction of the liver in the form of a passing increase in ALT activity, IS, Alkaline phosphatase, serum lactate dehydrogenase and bilirubin; rarely – jaundice.

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

From the nervous system: dizziness, headache; rarely – convulsions (when administered in high doses).

From the hematopoietic system: granulocytopenia, eozinofilija, leukopenia; rarely – anemia, thrombocytopenia, pancytopenia and agranulocytosis (<1%).

Cardio-vascular system: peripheral edema, feeling of chest discomfort, a feeling of tightness in the chest, cardiopalmus,

From the urinary system: rarely – impairment of renal function, increased concentration of urea in the blood, proteinuria.

Local reactions: soreness and infiltration at the site of intramuscular injection, pain along the vein; rarely – phlebitis.

Allergic reactions: hives, chills or fever, rash, itch, cough, bronchospasm; rarely – anaphylactic shock (<1%).

Other: rarely – thirst, fever, malaise, electrolyte imbalance (sodium and potassium).

Contraindications

- hypersensitivity to fosfomycin.

C caution the drug should be prescribed in case of a predisposition to allergic diseases, liver diseases, cardiac and renal failure, hypertension, elderly patients.

Pregnancy and lactation

Urophosphabol use^® in pregnant women is possible in cases, when the intended benefits to the mother outweighs the potential risk to the fetus, and should be administered under the supervision of a specialist.

Fosfomycin in very low concentrations is excreted in breast milk. When prescribing Urofosfabol^® lactation should be careful.

Cautions

Since Urofosfabol^® It contains 14.5 mEq sodium per 1 g product, electrolyte disturbances are possible. Care must be taken when choosing a dose when administering the drug to elderly patients., who need to reduce their sodium intake due to heart or kidney failure, hypertension.

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

To prevent the development of phlebitis or soreness at the injection site, for intravenous administration, it is recommended to use large amounts of solvent, and the rate of introduction should be as slow as possible.

Urophosphobol^® in high doses it is recommended to inject intravenously drip.

In the case of long-term treatment, it is recommended to periodically monitor liver and kidney function., as well as general and biochemical blood tests.

Overdose

Data on overdose are not provided.

Drug Interactions

In combination with penicillins, cephalosporins, carbapenems, aminoglikozidami, glycopeptides and fluoroquinolones fosfomycin exhibits a pronounced synergistic effect. This property of the drug is used in the treatment of infections., caused by multidrug-resistant pathogens (methicillin-resistant staphylococci, enterococci, enterobacteria, Pseudomonas aeruginosa).

Pharmaceutical interaction

Compatible with penicillin in solutions, karbenicillinom, chloramphenicol and streptomycin. Due to possible pharmaceutical incompatibility, do not mix Urophosphabol solution^® with solutions of other antibiotics.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 2 year.