Урофосфабол®

General characteristics. Structure:

Active ingredient: 1,4 g or 4,0 g of a fosfomitsin of dinatrium (in recalculation in фосфомицин).
Excipient: succinic acid.
 
Antibiotic of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Bactericidal action of a fosfomitsin is based on disturbance (at early stages) synthesis of a peptidoglikan of a cell wall of bacteria. Getting into a microbic cell on systems of transport of D - glucose-6-phosphate, drug it is irreversible inhibits УДФ-N-ацетилглюкозамиенолпирувилтрансферазу enzyme which catalyzes reaction of education UDF-N-atsetil-3-O-(1 carboxyvinyl) - a D-glycosamine from a fosfoyenolpiruvat and an UDF-N-atsetil-D-glyukozamina.

Fosfomitsin is active concerning gram-positive aerobes - Staphylococcus aureus, Staphylococcus epidermidis (including some strains steady against Methicillinum), Staphylococcus spp., Streptococcus pyogenes, Streptococcus spp. viridans groups, streptococci of the groups C, F, G, Streptococcus pneumoniae, Enterococcus faecalis, Bacillus anthracis; gram-negative aerobes - Aeromonas hydrophila, Citrobacter spp., Campylobacter jejuni, Escherichia coli, Enterobacter spp. (are moderately sensitive), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca (are moderately sensitive), Morganella morganii (the majority of strains are moderately sensitive), Neisseria gonorrhoeae, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri (are moderately sensitive), Pseudomonas aeruginosa, Serratia marcescens, Salmonella spp., Shigella spp., Vibrio spp. (are moderately sensitive), Yersinia enterocolitica; and also some anaerobe bacterias - Actinomyces spp., Peptococcus spp., Peptostreptococcus spp., Fusobacterium spp., Veillonella spp., Clostridium perfringens and Prevotella spp are moderately sensitive.

Enterococcus faecium, Acinetobacter spp are steady., Legionella spp., Borrelia spp., Listeria monocytogenes, Mycobacterium spp., Bacteroides spp., majority of intracellular activators (Coxiella burnetii, Rickettsia spp., Chlamydia spp., Mycoplasma pneumoniae, Ureaplasma urealyticum).

Secondary resistance of microorganisms to Urofosfabolu® develops seldom. Valuable property of drug is lack of cross resistance with other antibacterial agents. At a combination to beta lactams, ftorkhinolona, glycopeptides or aminoglycosides the expressed synergism of antimicrobic action concerning a wide range of gram-positive and gram-negative aerobic bacteria is noted.

Pharmacokinetics. In 15 min. after intravenous administration of 1 g of a fosfomitsin concentration of an antibiotic in blood serum makes 46 mg/l; in an hour it decreases twice. At slow (within 30-40 min.) infusions of high doses of drug (to 4 g there are each 6 hours) the maximum concentration not less than 250 mg/l; in intervals between introductions the maintenance of a fosfomitsin in plasma does not fall lower than 20 mg/l. At children at slow (within 60 min.) intravenous infusion at the rate of 25 mg/kg and 50 mg/kg, in 30 min. serumal concentration make 55,5 mg/l and 118,8 mg/l; in an hour - 34,2 mg/l and 89,7 mg/l, respectively.

Extent of linkng of a fosfomitsin with proteins of a blood plasma low - 1% of the entered dose.

Thanks to low molecular weight, фосфомицин it is well distributed in many bodies and body tissues. Bactericidal concentration are defined in tissue of a lung, pleural liquid, peritoneal liquid, bile, podkozhnozhirovy cellulose, muscles, bones, synovial fluid, eye tissues, an endocardium of valves of heart; quickly gets through a blood-brain barrier.

Concentration of drug considerably increases in cerebrospinal fluid at an inflammation of a meninx. Gets and collects in phagocytes (neutrophils and macrophages). Gets through a placenta. In small concentration gets into breast milk.

The elimination half-life (Т½) makes, on average, 1,5-2 hours at adults and from 0,69 to 1,04 hours, depending on a dose, at children. The main way of excretion of a fosfomitsin - renal (90-100% of the entered dose within a day); with urine the active form of drug is removed. A small part of the entered antibiotic is excreted through intestines, however, this way of elimination has no essential value. Fosfomitsin can be easily removed from plasma at a hemodialysis.

Indications to use:

The infectious and inflammatory diseases caused by activators, sensitive to drug:
- infections of soft tissues, including at patients with disturbances of peripheric circulation (a diabetes mellitus, diseases of arteries of the lower extremities), infections of burn wounds;
- infections of bones and joints;
- lower respiratory tract infections, including pneumonia and infections at patients with a mucoviscidosis;
- intraabdominal infections: acute cholecystitis, cholangitis, peritonitis;
- infectious and inflammatory diseases of bodies of a small pelvis: salpingitis, endometritis, pelviperitonitis;
- infections of urinary tract, including acute and exacerbation of chronic pyelonephritis

At the following diseases use of combinations of Urofosfabola® with antibiotics of other groups is recommended:
- infections of the central nervous system: bacterial meningitis, including postoperative;
- bacterial endocarditis;
- sepsis.

Route of administration and doses:

The average dose ^{of Urofosfabola®} at adults makes 2-4 g which is entered by each 6-8 hours.

At children, since the period of a neonatality, ^{Urofosfabol®} enter at the rate of 200-400 mg/kg of body weight a day. The daily dose is divided into 3 introductions; intervals between introductions make 8 hours.

Correction of the modes of introduction is required from patients with a renal failure and the patients who are on a hemodialysis
^{Урофосфабола®} (see the table):

Clearance of creatinine	40-20 ml/min.	20-10 ml/min.	<10 ml/min.
Dose/mode	To 2-4 g there are each 12 hours	To 2-4 g there are each 24 hours	To 2-4 g there are each 48 hours

The patient who is on a hemodialysis enter 2-4 g after each procedure of dialysis.

Way of preparation of solutions and introduction.

1. for direct introduction of 2 g ^{of Urofosfabola®} in/in jet to dissolve in 20 ml of water for injections (10 ml of solvent on 1 g ^{of Urofosfabola®}); to enter slowly within 5 min. (the recommended dosing mode - to 2 g is each 6-8 hours); 
2. for bystry in/in infusion of 4 g ^{of Urofosfabola®} to dissolve in 20 ml of water for injections; to add the turned-out solution to 100-200 ml of the compatible infusional environment; to enter during ½-1 hour (the recommended dosing mode - to 4 g is each 6-8 hours);
3. for long drop introduction of 4 g (in some clinical cases - 8 g) to dissolve ^{Urofosfabola®} in 20 ml of water for injections; to add the received solution to 200-500 ml of compatible liquid for infusions and to enter within 1-3 hours (the recommended mode - to 4 g is each 6-8 hours).

At dissolution ^{of Urofosfabola®} exothermic reaction is possible.
Compatible perfused liquids:
- 0,9% chloride sodium solution (normal saline solution)
- 5% glucose solution
- Ringer's solution
- Ringer's solution with a lactate

Features of use:

Necessary precautionary measures. As Urofosfabol® contains 14,5 мЭкв sodium on 1 g of drug, electrolytic disturbances are possible. It is necessary to be careful at the choice of a dose for administration of drug by the elderly patient which need reduction of consumption of sodium owing to a heart or renal failure, arterial hypertension, etc.
The precautionary measures concerning administration of drug.

For the prevention of development of phlebitis or morbidity in an injection site, at direct intravenous administration it is recommended to use large amounts of solvent, and rate of administering has to be slower; high doses of Urofosfabola® are recommended to be entered intravenously kapelno always when it is possible.

Other precautionary measures. In case of prolonged treatment this medicine recommends to control function of a liver and kidneys periodically (including according to biochemical analysis of blood: to content of electrolytes, urea nitrogen, bilirubin, activity of liver enzymes), and also indicators of the general blood test.

Side effects:

For a fosfomitsin the minimum toxicity is inherent; therapy is usually well transferred, undesirable medicinal reactions are observed seldom.

Allergic reactions: a small tortoiseshell, a fever or fever, rash, an itch, cough, a bronchospasm, it is very rare - an acute anaphylaxis (<1%).

From a liver and biliary tract: the abnormal liver function in the form of the taking place increase in activity of alaninaminotranspherase, an aspartaminotransferaza, an alkaline phosphatase, a lactate dehydrogenase and concentration of bilirubin in blood serum, is very rare - jaundice.

From the alimentary system: diarrhea, it is rare - stomatitis, nausea, vomiting, an abdominal pain, anorexia.
From system of blood: a granulocytopenia, an eosinophilia, a leukopenia, it is very rare - anemia, thrombocytopenia, a pancytopenia and an agranulocytosis (<1%).

From an urinary system: seldom - a renal failure, increase in concentration of urea in blood, a proteinuria, an imbalance of electrolytes (sodium and potassium).

From a nervous system: dizziness, is very rare - spasms (at introduction in high doses).

Local reactions: morbidity on the course of a vein in which make injections it is rare - phlebitis.

Others: seldom - a headache, thirst, fever, an indisposition, peripheral hypostases, a sensation of discomfort in breasts, feeling of squeezing in a thorax, a cardiopalmus.

Interaction with other medicines:

In combinations with penicillin, cephalosporins, karbapenema, aminoglycosides, glycopeptides and ftorkhinolona фосфомицин shows the expressed sinergidny effect; this property of drug is used at therapy of heavy infections, and also the infections caused by polyresistant activators (metitsillinustoychivy stafilokokka, enterococci, enterobakteriya, Pseudomonas aeruginosa, etc.).

In solutions it is compatible to penicillin, karbenitsilliny, chloramphenicol and streptomycin. In view of possible pharmaceutical incompatibility it is not necessary to mix Urofosfabola® solution with solutions of other antibiotics.

Contraindications:

Individual hypersensitivity to a fosfomitsin.

With care: allergic reactions to medicines in the anamnesis; serious illness of a liver; heart and renal failure; at elderly patients; at arterial hypertension.

Use ^{of Urofosfabola®} for pregnant women perhaps in cases when the estimated advantage for mother exceeds potential risk for a fruit, and has to be carried out under observation of the specialist.

Fosfomitsin in very small concentration gets into breast milk. At purpose ^{of Urofosfabola®} in the period of a lactation it is necessary to stop breastfeeding.

Overdose:

There are no messages on overdose of a fosfomitsin. Probable manifestations of acute overdose - hypernatremia symptoms (weakness, neuromuscular arousing, drowsiness, confusion of consciousness).
Treatment: symptomatic and maintenance therapy, compensation administration of liquid and artificial diuresis; in hard cases - a hemodialysis.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous administration of 1,0 g and 4,0 g.

On 1 g or 4 g of active agent in bottles glass, with a capacity of 10 ml and 20 ml respectively.

1 bottle with drug together with the application instruction is placed in a pack from a cardboard.