Zatsef time. for solution for infection. 1 g fl. No. 5

Pharmacological properties

Pharmacodynamics

Ceftazidime — a bactericidal tsefalosporinovy antibiotic which mechanism of action is connected with disturbance of synthesis of walls of a bacterial cell. It is highly active concerning a wide range of gram-positive and gram-negative bacteria, including the strains resistant to gentamycin and other aminoglycosides. It is very resistant to action of the majority β-лактамаз, produced by both gram-positive, and gram-negative microorganisms. The ceftazidime shows high activity of invitro and works within the narrow range of MIK for the majority of causative agents of infections.

Ceftazidime is active

concerning the following microorganisms:

Gram-negative

Pseudomonas aeruginosa, Pseudomonasspp. (vklyuchayaps. pseudomallei), Escherichia coli, Klebsiellaspp. (including Klebsiella pneumoniae), Proteus mirabilis, Proteus vulgaris, Morganella morganii (Proteus morganii), Proteus rettgeri, Providenciaspp., Enterobacterspp., Citrobacterspp., Serratiaspp., Salmonellaspp., Shigellaspp., Yersinia enterocolitica, Pasteurella multocida, Acinetobacterspp., Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae (including ampitsillinrezistentny strains), Haemophilus parainfluenzae (including ampitsillinrezistentny strains).

Gram-positive

Staphylococcus aureus (strains sensitive to Methicillinum), Staphylococcus epidermidis (strains sensitive to Methicillinum), Micrococcusspp., Streptococcus pyogenes (β-hemolytic streptococci of group A), Streptococcusgruppy B (Strept. agalactiae), Streptococcus pneumoniae, Streptococcus mitis, Streptococcusspp. (excepting Streptococcus faecalis).

Anaerobic

Peptococcusspp., Peptostreptococcusspp., Streptococcusspp., Propionibacteriumspp., Clostridium perfringens, Fusobacteriumspp., Bacteroidesspp. (many strains of Bacteroides fragilis of a rezistentna to drug).

Ceftazidime does not affect with invitro resistant to Methicillinum staphylococcus, Streptococcus faecalis and many other enterococci, Listeria monocytogenes, Campylobacterspp. and Clostridium difficile.

Pharmacokinetics

After an injection of medicament in oil in a dose of 500 mg and 1 g is quickly reached by the C _max in blood plasma which averages 18 and 37 mg/l respectively. In 5 min. later in/in bolyusny administrations of medicament in a dose of 500 mg, 1 or 2 g in blood serum are reached concentration on average 46; 87 or 170 mg/l respectively. Therapeutic effective concentration in blood serum remain even in 8–12 h later in/in and introductions in oil. Linking with proteins of blood plasma makes about 10%. The concentration of a ceftazidime exceeding MIK for the majority of widespread pathogenic microorganisms is reached in such fabrics and environments of an organism as a bone tissue, heart tissues, bile, a phlegm, intraocular, synovial, pleural and peritoneal fluid. The ceftazidime quickly gets through a placenta and is excreted in ore milk. Drug badly gets through the intact GEB, in the absence of inflammation the concentration of medicament in central nervous system is low. However at inflammation of a meninx the concentration of a ceftazidime in central nervous system reaches 4–20 mg/l and above that corresponds to the level of its therapeutic concentration.

Ceftazidime is not metabolized by

in an organism. After parenteral administration high and resistant concentration of a ceftazidime in blood serum is reached. Its T _½ makes about 2 h. Drug is removed out of the changed look, in an active form with urine by glomerular filtration; about 80-90% of a dose are removed with urine during 24 h. At patients with a renal failure the elimination of a ceftazidime decreases that demands a medicament dose decline. Less than 1% of medicament are removed with bile that considerably limits amount of the medicament getting into intestines.

Indication

Ceftazidime is appointed for treatment mono - and the multi-infections caused by microorganisms, sensitive to it: heavy infections: sepsis, bacteremia, peritonitis, meningitis; infections at patients with reduced immunity; patients of intensive care units, for example with the infected burns; respiratory infections, including infections of lungs at patients with a mucoviscidosis; infections of ENT organs; infections of urinary tract; infections of skin and soft tissues; infections of a GIT, bilious ways and abdominal cavity; infections of bones and joints; the infections connected with haemo - both peritoneal dialysis and continuous out-patient peritoneal dialysis.

Prevention of infections: infections at surgeries on a prostate (transurethral resection).

Use

Dose of medicament depends on disease severity, sensitivity, localization and like an infection and also on age and a functional condition of kidneys of the patient.

Use for adults

Daily dose for adults makes 1–6 g in 2–3 introductions in the way in / twisted injections in oil.

Infection of urinogenital bodies and less heavy infections: 500 mg — 1 g each 12 h

Majority of infections: 1 g each 8 h or 2 g — each 12 h

Especially heavy infections, especially at patients with an immunodeficiency, including patients with a neutropenia: on 2 g each 8–12 h or on 3 g — each 12 h

Mucoviscidosis in combination with a pyocyanic infection of lungs: from 100 to 150 mg/kg of body weight a day in 3 introductions.

daily dose can make

At adults with normal function of kidneys to 9 g

At use for prevention at surgeries on a prostate enter 1 g of medicament of anesthesia induction in time. The second dose is entered into the moment of removal of a catheter.

Use for babies and children is aged more senior than 2 months

Appoint in a dose 30–10 mg/kg/days in 2–3 receptions. Children with an immunodeficiency, a mucoviscidosis or meningitis are recommended to administer the medicament in a dose to 150 mg/kg/days (as much as possible — 6 g/days) in 3 introductions.

by

Use for children aged up to 2 months, including at newborns

Drug appoint in a dose 25–60 mg/kg/days in 2 receptions. At newborn T _½ a ceftazidime from blood serum can be by 3–4 times more long, than at adults.

Use for patients of advanced age

Taking into account decrease in clearance of a ceftazidime at patients of advanced age with acute infections the daily dose should not exceed 3 g, especially for patients 80 years are aged more senior.

Dosing at patients with a renal failure

Ceftazidime is allocated to

with kidneys out of the changed look therefore the medicament dose at patients with a renal failure has to be reduced. The initial dose has to make 1 g. Definition of a maintenance dose (tab. 1) it is necessary to carry out suchety glomerular filtration rates.

to

Table 1

by

Recommended maintenance doses of a ceftazidime in a renal failure

Clearance of creatinine, ml/min.	Approximate level of creatinine in blood serum, µmol/l (mg/dl)	Recommended single dose of a ceftazidime,	Interval between introductions, h
> 50	<150 (<1.7)	Correction of the mode of dosing it is not required
50-31	150-200 (1.7-2.3)	1.0	12
30-16	200-350 (2.3-4.0)	1.0	24
15-6	350-500 (4.0-5.6)	0.5	24
<5	> 500 (> 5.6)	0.5	48

At patients with heavy infections a single dose can be raised for 50% or to respectively increase the frequency of administration of drug. At these patients it is recommended to control ceftazidime level in blood serum which should not exceed 40 mg/l.

At children estimated clearance of creatinine should be skorrigirovat taking into account the surface area of a body or body weight.

Use for the patients who are on a hemodialysis

T _½ a ceftazidime of a hemodialysis makes in time 3–5 h of blood serum. After each session of a hemodialysis it is necessary to enter the supporting recommended ceftazidime dose (see the above-stated table).

Use for the patients who are on peritoneal dialysis

Ceftazidime can be applied at peritoneal dialysis in the usual mode and at long out-patient peritoneal dialysis. Krom in to introductions, solution of a ceftazidime it is possible to add to dialysis liquid (usually at the rate of 125–250 mg on 2 l of dialysis liquid).

recommended dose makes

At patients with a renal failure which carries out a long arteriovenous hemodialysis or high-speed haemo filtration in intensive care units 1g/days in the form of a single dose or in stages. With a low speed it is necessary to apply doses to haemo filtration, as well as in a renal failure.

recommendations a podozirovaniya are provided by

At patients to whom venovenozny haemo filtration and a venovenozny hemodialysis is carried out in tab. 2 and 3.

Table 2

Recommendation to a ceftazidime podozirovaniye for patients to whom long venovenozny haemo filtration

by

Residual function of kidneys is carried out (clearance of creatinine, ml/min.)	Maintenance dose (mg) of a vzavisimost of an otskorost of ultrafiltration, *
	5	16.7	33.3	50
0	250	250	500	500
5	250	250	500	500
10	250	500	500	750
15	250	500	500	750
20	500	500	500	750

* the Maintenance dose has to be entered by ml/min. each 12 h.

Table 3

Recommendation to a ceftazidime podozirovaniye for patients to whom the long venovenozny hemodialysis

by by

Residual function of kidneys is carried out (clearance of creatinine, ml/min.)	Maintenance dose (mg) depending on the speed of ultrafiltration, ml/min. *
	1.0 l/h			2.0 l/h
	Speed of ultrafiltration, l/h			Speed of ultrafiltration, l/h
	0.5	1.0	2.0	0.5	1.0	2.0
0	500	500	500	500	500	750
5	500	500	750	500	500	750
10	500	500	750	500	750	1000
15	500	750	750	750	750	1000
20	750	750	1000	750	750	1000

* the Maintenance dose has to be entered each 12 h

Preparation and administration of solution of medicament

Zatsef enter in / twisted by a deep injection in oil. The recommended sites for introduction in oil are the upper external quadrant of a big gluteus or a lateral part of a hip.

Solutions of a ceftazidime can be entered directly into a vein or into a system for in/in infusions if the patient receives solutions parenterally (tab. 4).

Table 4

Instruction for preparation of solutions of a ceftazidime

Entered dose and a method of administration		Necessary amount of solvent, ml	Approximate concentration of drug, mg/ml
1 g	In oil	3	260
	In/in bolyusno	10	90
	In/in by drop infusion	50 *	20

* Dissolution it is necessary to carry out in two steps (see further).

Zatsef is compatible

to the majority of widely applied solutions for in/in introductions. However it is not necessary to apply as solvent Natrii hydrocarbonas to injections (see INTERACTIONS).

Colour of solution varies

from light yellow to amber depending on concentration, solvent and storage conditions. At observance of recommendations the effect of medicament does not depend on variations of its coloring.

Ceftazidime in concentration from 1–40 mg/ml is compatible

to such solutions: 0.9% chloride sodium solution; 6/Mr-r lactate sodium; Gartman's solution; 5% glucose solution; 0.225% chloride sodium solution in 5% glucose solution; 0.45% chloride sodium solution in 5% eglyukoza solution; 0.9% chloride sodium solution in 5% glucose solution; 0.18% chloride sodium solution in 4% glucose solution; 10% glucose solution; 10% solution of a dextran 40 in 0.9% chloride sodium solution; 10% solution of a dextran 40 in 5% r-reglyukozy; 6% solution of a dextran 70 in 0.9% chloride sodium solution; 6% solution of a dextran 70 in 5% r-reglyukozy.

Ceftazidime in concentration of 0.05-0.25 mg/ml is compatible

to liquid for intraperitoneal dialysis (lactate).

Ceftazidime for introduction in oil is dissolved in 0.5% or 1% r-relidokaina.

Efficiency of both medicaments remains when mixing a ceftazidime in a dose of 4 mg/ml with such substances: a hydrocortisone (a sodium hydrocortisone phosphate) 1mg/ml in 0.9% solution of sodium of chloride or 0.5% glucose solution; tsefuroksy (tsefuroksy sodium) 3 mg/ml in 0.9% chloride sodium solution; kloksatsillin (kloksatsillin sodium) 4mg/ml in 0.9% chloride sodium solution; ME/ml heparin 10 or 5 ME/ml in 0.9% chloride sodium solution; potassium chloride 10 mekv/l or 40 mekv/lv 0.9% chloride sodium solution.

For preparation of solution for in oil or in in a bolyusny injection should stick the hypodermic needle through a cover of a bottle and to enter the recommended solvent volume; to take out the hypodermic needle and to stir up a bottle of a dopolucheniye of transparent solution; to turn a bottle, at completely entered piston of the syringe to insert a needle into a bottle; to aspirate all solution in the syringe, at the same time the needle has to be in solution all the time.

For preparation of solution for should stick the hypodermic needle through a cover of a bottle in in infusions and to enter 10 ml of solvent; to take out the hypodermic needle and to stir up a bottle of a dopolucheniye of transparent solution; to insert an air tubule through a cover into a bottle for increase in pressure; without taking out an air tubule, to add 40 more ml of solvent; to take out an air tubule, to stir up a bottle and to adjust a system for infusions regularly. To provide sterility of drug, it is very important not to insert an air tubule through a cover before medicament dissolution.

Contraindication

hypersensitivity to a ceftazidime to pentahydrate or other components of drug, other β-laktamny antibiotics.

Side effects

Note

seldom.

Local: phlebitis or thrombophlebitis at in in introduction; pain and/or inflammation together injections in oil.

Reaction of hypersensitivity: makulopapulezny rashes or urticaria, fever, an itching, it is very rare — a Quincke's disease and an anaphylaxis (including a bronchospasm and/or arterial hypotension). Can note a polymorphic erythema, Stephens's syndrome — Johnson and a toxic epidermal necrolysis.

from a GIT: diarrhea, nausea, vomiting, an abdominal pain, it is very rare — candidosis stomatitis and colitis. As well as at use of other cephalosporins, colitis can be connected by cClostridium difficile and proceed sweat to Yip of pseudomembranous colitis.

from an urinogenital system: candidiasis, vaginitis.

from a gepatobiliarny system and a pancreas: very seldom — jaundice.

from central nervous system: headache, dizziness, paresthesias and disturbance of taste. It was reported about cases of neurologic complications, such as tremor, myoclonus, spasms, encephalopathy and coma at patients with a renal failure at which the dose of a ceftazidime was not respectively reduced.

Change of laboratory indicators (passing): an eosinophilia, positive reaction of Koombs (can influence blood typing), it is very rare — hemolytic anemia, a thrombocytosis and increase in level of one or several liver enzymes (AlAT, AsAT, LDG, gamma glutariltranspeptidaza, SF). Perhaps tranzitorny increase in level of urea of blood, urea nitrogen of blood and/or creatinine in blood serum. The leukopenia, a neutropenia, an agranulocytosis, thrombocytopenia or mfotsitoz are very seldom possible.

Special instructions should establish to

Prior to treatment by

existence at the patient in the anamnesis of reactions of hypersensitivity to a ceftazidime, cephalosporins, penicillin or other medicines.

needs to appoint by

With extra care a ceftazidime to patients who in the anamnesis had an allergic reaction to penicillin or other β-laktamny antibiotics. In case of allergic reaction to a ceftazidime it is necessary to stop medicament use immediately. Heavy reactions of hypersensitivity can demand use of epinephrine, a hydrocortisone, antihistaminic medicaments and other means of emergency aid.

Simultaneous treatment by high doses of cephalosporins and nephrotoxic drugs, such as aminoglycosides or highly active diuretics (for example furosemide), can adversely influence function of kidneys. At observance of the recommended dosing it is the phenomenon it is improbable. Is not present germinated about adverse influence a ceftazidime on function in usual therapeutic doses.

Ceftazidime is allocated to

with kidneys therefore the dose should be reduced depending on extent of damage of kidneys. In the absence of adequate dose adjustment the development of neurologic complications is possible.

As well as at use of other antibiotics of a broad spectrum of activity, long treatment by Zatsef can lead to the overgrowth of microorganisms, insensitive to it (for example mushrooms rodacandida, enterococci); in this case there can be a need for the termination of treatment or acceptance of other necessary measures. It is very important to control a condition of the patient constantly.

As well as at use of other cephalosporins and penicillin of a broad spectrum of activity, some earlier sensitive shtammyenterobacterspp. iserratiaspp. there can be resistant treatments a ceftazidime in time. It is in this situation recommended to conduct a research of sensitivity of microorganisms periodically.

Ceftazidime does not affect results of definition of a glucosuria by enzymatic methods, nevertheless insignificant influence on results of the analysis can be noted at use of methods of restoration of copper (Benedikta, Felinga, use Klinitesta).

Ceftazidime does not affect results of definition of creatinine alkaline pikratnym by method.

Period of pregnancy and feeding by a breast

is not present

Experimental data about embriotoksichesky and teratogenic actions of a ceftazidime, however it it is necessary to appoint with care for the first time months of pregnancy and to children of chest age.

Ceftazidime in small amounts is allocated to

with breast milk therefore it is necessary to appoint it with care during feeding by a breast.

Children

use Drug at children. With care it is necessary to use medicament for treatment of newborns.

Ability to influence speed of response at control of vehicles and work with other mechanisms

was not studied by

.

Interaction

Simultaneous use of medicament in high doses with nephrotoxic medicaments can have negative effect on function of kidneys.

invitro Chloramphenicol is an antagonist of a ceftazidime and other cephalosporins. The clinical value of this phenomenon is unknown, nevertheless, if simultaneous use of Zatsef with chloramphenicol is offered, it is necessary to consider a possibility of antagonistic action.

Incompatibility. Zatsef is less stable in Natrii hydrocarbonas solution for injections, than in other solutions for in / vv maintaining therefore the last is not recommended to be used as solvent.

Ceftazidime and aminoglycosides should not be mixed a water infusional system or the syringe.

At addition of Vancomycinum to solution of a ceftazidime the formation of a deposit therefore it is recommended to wash out the infusional systems of willows / in catheters between use of these two medicaments is possible

.

Overdose

Overdose can lead

to development of neurologic complications — encephalopathies, spasms, a coma. Symptomatic treatment. Concentration of a ceftazidime in blood serum can be reduced by carrying out a hemodialysis or peritoneal dialysis.

Storage conditions

B the dry, protected a reflected light place at a temperature are not present above 25 °C.