Pharmacological properties

Pharmacodynamics

Tsefuroksim is the bactericidal tsefalosporinovy antibiotic having high activity concerning a wide range of gram-positive and gram-negative bacteria including the strains producing β-lactamelements. tsefuroksy it is resistant to action β-лактамаз and therefore, respectively, shows activity concerning many ampicillin - or amoksitsillinrezistentny strains. the main mechanism of bactericidal action — disturbance of synthesis of a wall of a bacterial cell.

Acquired resistance to an antibiotic differs in

in different regions and can change over time, and for separate strains can significantly differ. It is desirable to address local data on sensitivity to an antibiotic, especially at treatment of heavy infections.

Drug is highly active

against Staphylococcus aureus, including the strains resistant to penicillin (but not to the single strains resistant to Methicillinum), Staphylococcus epidermidis, Haemophilus influenza, Klebsiella spp., Enterobacter spp., Streptococcus pyogenes, Escherichia coli, Streptococcus mitis (viridians group), Clostridium spp., Proteus mitabilis, Proteus rettgeri, Salmonella typhi, Salmonella typhimurium and other strains of Salmonella, Shigella spp., Neisseria spp. (including the strains of N. gonorrhea producing β-lactamelements), Bordetella pertussis. Drug reveals moderate sensitivity against Proteus vulgaris, Morganella morganii (Proteus morganii) and Bacterides fragilis.

Microorganisms insensitive to a tsefuroksim: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Legionella spp., metitsillinrezistentny strains of Staphylococcus aureus and Staphylococcus epidermidis.

Strains which also were insensitive to a tsefuroksim: Streptococcus faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp. and Bacteroides fragilis.

In vitro tsefuroksy in a combination with aminoglikozidny antibiotics has at least additive effect, sometimes with signs of synergism.

Pharmacokinetics

C _max a tsefuroksim in blood plasma is noted in 30–45 min. after introduction in oil. T _½ tsefuroksima at in/in and introduction in oil makes about 70 min. Simultaneous introduction of a probenetsid slows down removal of a tsefuroksim and causes increase in its concentration in blood plasma.

Linking with proteins of blood plasma fluctuates from 33 to 50%.

medicament almost completely (85–90%) is removed by

During 24 h from the moment of introduction in not changed view with urine, the most part of medicament — in the first 6 h Tsefuroksim is not metabolized and removed by glomerular filtration and canalicular secretion.

Level of a tsefuroksim in blood plasma decreases when carrying out dialysis.

Concentration of a tsefuroksim exceeding the minimum inhibiting concentration for the majority of widespread pathogenic microorganisms is reached by

in a bone tissue, synovial and intraocular liquids. Tsefuroksim gets through GEB at inflammation of a meninx.

Indication

Treatment of the infections caused by microorganisms, sensitive to a tsefuroksim, or treatment of infections before definition of agent of infection.

Infectious diseases of airways: the acute and chronic bronchitis infected bronchiectasias, bacterial pneumonia, abscess of lungs, postoperative infections of bodies of a thorax.

Infectious diseases of a throat, nose: sinusitis, tonsillitis, pharyngitis.

Infectious diseases of urinary tract: acute and chronic pyelonephritis, cystitis, asymptomatic bacteriurias.

Infectious diseases of soft tissues: cellulitis, erizipeloid, wound fevers.

Infectious diseases of bones and joints: osteomyelitis, septic arthritises.

Infection in obstetrics and gynecology: infectious and inflammatory diseases of bodies of a basin.

Gonorrhoea, especially when penicillin is contraindicated.

Other infectious diseases, including a septicaemia and meningitis.

Prevention of emergence of infectious complications after thorax and abdominal cavity surgeries, on bodies of a basin, at vascular, cardiovascular and orthopedic surgical interventions.

In most cases monotherapy by Kimatsef is effective

, but if necessary medicament can be used in a combination with aminoglikozidny antibiotics or with metronidazole (orally, in suppositories or injektsionno).

in case of the available or expected mixed aerobic and mephitic gangrene (for example peritonitis, aspiration pneumonia, abscess of lungs, bodies of a basin and a brain) and a high probability of such infection (for example at a large intestine surgeries and in gynecologic surgery) acceptable is Kimatsef's use in a combination with metronidazole.

Kimatsef can appoint

At treatment of pneumonia and exacerbation of chronic bronchitis before oral administration of a tsefuroksim of an aksetil, when necessary.

Use

before therapy using a tsefuroksim needs to exclude existence at the patient of intolerance of drug, having taken skin samples. the sensitivity to a kimatsef differs in different regions and can change over time. if necessary it is necessary to address local data on a sensitivity a reason for an antibiotic.

are only intended to

Injection of Kimatsef for in/in or introductions in oil.

As tsefuroksy is issued also in the form of a tsefuroksim of an aksetil for oral administration, it is possible to pass consistently from parenteral therapy by Kimatsef to peroral when it is clinically reasonable.

General recommendations

Adult. In many infections 3 times in day in oil or in / there are enough 750 mg century. In heavier infections the dose is raised to 1.5 g by 3 times a day in / century. In case of need the frequency of introduction can be increased to 4 times a day (an introduction interval — 6 h), the general dose in day raise up to 3–6 g. In case of need in some infections it is possible to carry out treatment according to such scheme: 750 mg or 1.5 g 2 times a day (in/in or in oil) with the subsequent oral administration of a tsefuroksim.

Children. 30–100 mg/kg/days divided into 3–4 injections. For the majority of infections an optimum dose are 60 mg/kg/days

At newborns apply 30–100 mg/kg/days divided into 2–3 injections. It is necessary to consider that T _½ a tsefuroksima in the first weeks of life can be in 3–5 times more, than at adults.

Gonorrhoea. 1.5 g by 1 injection or on 750 mg in the form of 2 injections in oil in both buttocks.

Meningitis. Kimatsef apply as cure of monotherapy for bacterial meningitis if it is caused by sensitive strains.

Adult: 3 g in/in each 8 h

Children: 200–240 mg/kg/days in/in divided into 3 or 4 doses. Such dose can be reduced to 100 mg/kg/days in in the ambassador of 3 days of use or at clinical improvement.

For newborns the initial dose has to make 100 mg/kg/days in / century. The dose decline to 50 mg/kg/days in case of clinical improvement is possible.

Prevention. The usual dose makes 1.5 g in/in in a stage of induction of anesthesia at abdominal, pelvic and orthopedic operations. This dose can be added with introduction in oil of 750 mg of medicament in 8 and 16 h

At heart surgeries, lungs, a gullet and vessels a usual dose makes 1.5 g in/in which is entered at a stage of induction of anesthesia and then complement with introduction in oil 750 mg 3 times a day during the following 24–48 h

At full replacement of a joint of 1.5 g of powder of a tsefuroksim mix with one package of methylmethacrylate cement-polymer before addition of liquid monomer.

Consecutive therapy

Pneumonia: 1.5 g of Kimatsef 2–3 times a day (in oil or in / c) during 48–72 h, then it is necessary to pass to oral administration 500 mg of a tsefuroksim 2 times a day for 7–10 days.

Exacerbation of chronic bronchitis: 750 mg of Kimatsef 2–3 times a day (in oil or in / c) during 48–72 h, then it is necessary to pass to oral administration 500 mg of a tsefuroksim 2 times a day for 7 days.

Duration of both parenteral, and oral therapy is defined by weight of an infection and a clinical condition of the patient.

Renal failure. Tsefuroksim is allocated with kidneys. Therefore, as well as at use of other similar antibiotics, patients with impaired renal function are recommended to reduce Kimatsef's dose for compensation of slower excretion of drug. There is no need to reduce a standard dose (750 mg-1.5 of 3 times a day) if the level of clearance of creatinine is 20 ml/min. The dose of 750 mg 2 times a day, in more hard cases (clearance of creatinine of 10 ml/min.) — 750 mg of 1 times a day is recommended to adults with the profound renal failure (clearance of creatinine of 10-20 ml/min.).

At a hemodialysis needs to enter 750 mg in/in or dialysis, in oil at the end of each session. In addition to parenteral administration tsefuroksy it is possible to add to peritoneal dialysis liquid (usually 250 mg on each 2 l of dialysis liquid). For the patients who are on a program hemodialysis or high-line haemo filtration in intensive care units, the recommended dose makes 750 mg 2 times a day. Patients at whom carry out low-line haemo filtration should adhere to the scheme of dosing, as for treatment in a renal failure.

Feature of administration of drug. For introduction in oil it is necessary to add 3 ml of water for injections to 750 mg of Kimatsef. To stir up carefully before formation of opaque suspension.

For in/in introductions to dissolve 750 mg of Kimatsef in not less than 6 ml of water for injections, 1.5 g — in 15 ml. For infusions which last no more than 30 min. 1.5 g of a tsefuroksim can be dissolved in 50–100 ml of water for injections. The received solutions can be entered directly into a vein or into a dropper tube at infusional therapy.

Children. Apply at children from the first days of life.

Contraindication

Hypersensitivity to a tsefuroksim or other components of drug. hypersensitivity to tsefalosporinovy antibiotics. existence in the anamnesis of heavy hypersensitivity (for example anaphylactic reactions) to other β-laktamny antibiotics (penicillin, monobaktama and karbapenema).

Side effects

Side effects single (1/10,000) also have easy and reversible temper. the frequency of their emergence specified below is approximate as for the majority of reactions there are no sufficient data for detailed calculation. besides, the frequency of cases of side effects varies depending on indications.

Criteria for evaluation of frequency of emergence of side effects: very often (≥1/10); often (≥1/100 and 1/10); infrequently (≥1/1000 and 1/100); seldom (≥1/10,000 and 1/1000); very seldom (1/10,000).

Infection and invasion: seldom — the overgrowth of insensitive microorganisms, for example Candida.

from the system of blood and lymphatic system: often — a neutropenia, an eosinophilia; infrequently — a leukopenia, decrease in level of hemoglobin, positive test of Koombs; seldom — thrombocytopenia; very seldom — hemolytic anemia.

Cephalosporins have property to be absorbed on a surface of a membrane of erythrocytes and to interact with antibodies, causing positive test of Koombs that can influence blood typing and is very rare lead to development of hemolytic anemia.

from the immune system: the reactions of hypersensitivity including: infrequently — skin rash, a small tortoiseshell and an itching; seldom — medicamentous fever; very seldom — interstitial nephrite, an anaphylaxis, a skin vasculitis.

from a GIT: infrequently — discomfort in a GIT; very seldom — pseudomembranous colitis (see. Special INSTRUCTIONS).

Gepatobiliarny reactions: often — tranzitorny increase in level of liver enzymes; infrequently — tranzitorny increase in level of bilirubin.

Tranzitorny increase in level of hepatic enzymes or bilirubin arose mainly at patients with the existing liver pathology, but there are no data on toxic influence of medicament on a liver.

from skin and hypodermic fabrics: very seldom — a polymorphic erythema, Stephens's syndrome — Johnson and a toxic epidermal necrolysis.

from an urinary system: very seldom — increase in level of creatinine in blood plasma, urea nitrogen in blood and decrease in level of clearance of creatinine.

General disturbances and reactions in the injection site: often — the reactions in the injection site including pain and thrombophlebitis.

Developing of pain in the place in oil of introduction is more probable

at use of medicament in higher doses, however it should not be the cause of the termination of treatment.

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Special instructions

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As well as at use of other β-laktamny antibiotics, it was reported about heavy and sometimes lethal reactions of hypersensitivity. in case of heavy reactions of hypersensitivity treatment tsefuroksimy it is necessary to stop and take the appropriate urgent measures immediately.

should be determined by

Before an initiation of treatment at the patient existence in the anamnesis of heavy reactions of hypersensitivity to a tsefuroksim, tsefalosporinovy antibiotics or other β-laktamny antibiotics. With care appoint to patients at whom noted reactions of hypersensitivity to other β-laktamny antibiotics.

should appoint Tsefalosporinovy antibiotics in high doses by

with care the patient receiving treatment by strong diuretics, such as furosemide or aminoglikozidny antibiotics as it was reported about cases of undesirable influence on function of kidneys at such combination of drugs. Function of kidneys needs to be monitorirovat at these patients as patients of advanced age and also at persons with a renal failure (see USE).

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As well as at other schemes of treatment of meningitis, at several patients of children's age who received therapy tsefuroksimy registered cases of a hearing loss of average and heavy degree.

As well as at treatment by other antibiotics, in 18–36 h after an injection of a tsefuroksim in SMZh. However the clinical value of this phenomenon is unknown.

As well as at use of other antibiotics, prolonged use of a tsefuroksim can lead to the overgrowth of insensitive microorganisms (such as Candida, Enterococci, Clostridium difficile) that can demand the treatment termination.

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At use of antibiotics it was reported about cases of pseudomembranous colitis of varying severity: from easy to life-threatening. Therefore it is important to consider establishment of this diagnosis at patients who had a diarrhea in time or after use of an antibiotic. In case of long and considerable diarrhea or if the patient has abdominal spasms, treatment it is necessary to stop and perform further examination immediately.

time of transition to oral administration of a tsefuroksim is defined

At Kimatsef's use in the mode of consecutive therapy by weight of an infection, a clinical condition of the patient and sensitivity of a microorganism. In the absence of clinical improvement during 72 h it is necessary to continue parenteral administration of drug. Before use of oral medicament it is necessary to study the instruction for use of this drug.

Use during pregnancy and feeding by a breast. Data on embriotoksichesky and teratogenic action of a tsefuroksim are not received, however, as well as at use of other medicines, it is necessary to appoint it with care in the first months of pregnancy.

Tsefuroksim gets into breast milk therefore it is necessary to stop feeding by a breast during medicament use.

Ability to influence speed of response at control of vehicles or other mechanisms. There are no messages about influence of medicament on speed of response at control of vehicles or other mechanisms.

Interaction

As well as other antibiotics, tsefuroksy can influence intestinal microflora that leads to decrease in a reabsorption of estrogen and decrease in efficiency of the combined oral contraceptives.

At the patients accepting Kimatsef for determination of level of glucose in blood is recommended to use a glyukozooksidazny or hexokinase technique. Tsefuroksim does not affect results of definition of a glucosuria by fermental methods.

Tsefuroksim in insignificant degree can affect results of use of the techniques based on copper restoration (Benedikta, Fellinga, Klinitest), however it does not result in false positive results, as at use of some other cephalosporins.

Tsefuroksim does not affect result of determination of level of creatinine by means of alkaline picrate.

Incompatibility. It is impossible to mix tsefuroksy in one syringe with aminoglikozidny antibiotics. pH of 2.74% of solution of sodium bicarbonate for injections significantly affects color of solution therefore it is not recommended to apply to cultivation of a tsefuroksim. However in case of need, if the patient receives sodium bicarbonate solution in the way in to infusions, tsefuroksy it is possible to enter directly into a dropper tube.

1.5 g of a tsefuroksim, dissolved in 15 ml of water for injections, it is possible to use together with a metronidazole injection (500 mg / 100 ml), both medicaments keep the activity during 24 h at a temperature below 25 °C.

are compatible

1.5 g of a tsefuroksim to 1 g (in 15 ml of solvent) or from 5 g (in 50 ml of solvent) an azlotsillina during 24 h at a temperature of 4 °C and 6 h — at a temperature of 25 °C.

Tsefuroksim (5 mg/ml) can be stored for 24 h at a temperature of 25 °C of 5% or 10% solution of a ksilitol for injections.

Tsefuroksim is compatible

to the solutions containing up to 1% of lidocaine of a hydrochloride.

Tsefuroksim is compatible

to the majority of the all-applied solutions for in/in injections. It keeps the properties during 24 h at the room temperature in such solutions: 0.9% sodium chloride solution for injections; 5% glucose solution for injections; 0.18% sodium chloride solution from 4% glucose solution for injections; 5% glucose solution from 0.9% sodium chloride solution for injections; 5% glucose solution from 0.45% sodium chloride solution for injections; 5% glucose solution from 0.225% sodium chloride solution for injections; 10% glucose solution for injections; 10% solution of the inverted glucose in water for injections; Ringera solution; Ringera-laktata solution; M/6 lactate sodium solution; Hartman's solution.

Stability of a tsefuroksim in 0.9% sodium chloride solution for injections from 5% solution of glucose does not change in the presence of a phosphate sodium hydrocortisone.

Tsefuroksim is also compatible

during 24 h at the room temperature at cultivation in solution for infusions:

• with heparin (10 or 50 PIECES/ml) in 0.9% sodium chloride solution for injections;
• with potassium chloride solution (10 or 40 mekv/l) in 0.9% sodium chloride solution for injections.

Overdose

Overdose of tsefalosporinovy antibiotics can lead

to development of symptoms of irritation of a brain, spasms can be a consequence of what. concentration of a tsefuroksim in blood plasma can be reduced by a hemodialysis or peritoneal dialysis.

Storage conditions

In original packing at a temperature not above 25 °C. after cultivation for in/in or injections in oil medicament can be stored up to 48 h in the fridge (4 °C) or up to 5 h — at a temperature up to 25 °C.