Tseftazidim-akos

General characteristics. Structure:

Active ingredient: 0,5 g, 1,0 g and 2,0 g of a ceftazidime of pentahydrate of sodium of a carbonate (in terms of a ceftazidime).

Pharmacological properties:

Antibiotic of group of cephalosporins III of generation of a broad spectrum of activity for parenteral administration. Works bakteritsidno, breaking synthesis of a cell wall of microorganisms. It is steady against action of the majority β-лактамаз. Affects many strains steady against ampicillin and other cephalosporins.

Drug is active concerning gram-negative microorganisms: Pseudomonas spp. (including Pseudomonas aeruginosa), Klebsiella spp. (including Klebsiella pneumoniae), Proteus mirabilis, Proteus vulgaris, Escherichia coli, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Pasteurella multocida, Neisseria meningitidis, Haemophilus influenzae (including the strains steady against ampicillin); gram-positive microorganisms: Staphylococcus aureus (which are producing and not producing a penicillinase the strains sensitive to Methicillinum), Streptococcus pyogenes (group A a beta and hemolitic streptococcus), Streptococcus agalactiae (group B), Streptococcus pneumoniae; anaerobic microorganisms: Bacteroides spp. (but many strains of Bacteroides fragilis of a rezistentna).

in vitro against the majority of strains of the following microorganisms is active (clinical value of this activity is unknown): Clostridium perfringens, Acinetobacter spp., Haemophilus parainfluenzae, Morganella morganii, Neisseria gonorrhoeae, Peptococcus spp., Peptostreptococcus spp., Providencia spp., including Providencia rettgeri, Salmonella spp., Shigella spp., Staphylococcus epidermidis, Yersinia enterocolitica.

It is not active concerning steady against Staphylococcus spp Methicillinum., Streptococcus faecalis, Enterococcus spp.; Listeria monocytogenes, Campylobacter spp. and Clostridium difficile.

 

Pharmacokinetics. Absorption

After administration of drug in oil in a dose of 0.5 g or 1 g of Cmax it is reached in 1 h and makes respectively 17 mkg/ml and 39 mkg/ml; later in/in bolyusny introductions in doses of 0.5 g, 1 g or 2 g of Cmax are made by respectively 42 mkg/ml, 69 mkg/ml and 170 mkg/ml.

Therapeutic effective serumal concentration after in oil and in/in introductions remain during 8-12 h.

Distribution

Linkng with proteins of a blood plasma - 10%.

The concentration of a ceftazidime exceeding MPK for the majority of widespread pathogenic microorganisms can be reached in a bone tissue, tissues of heart, bile, a phlegm, synovial fluid, intraocular, pleural and peritoneal liquids. Easily gets through a placental barrier and it is allocated with breast milk. In the absence of inflammatory process in meningeal covers the ceftazidime badly gets through GEB, concentration of drug in cerebrospinal fluid low. At meningitis in cerebrospinal fluid the therapeutic concentration of a ceftazidime making 4-20 mg/l and above are reached.

Metabolism and removal

The ceftazidime is not metabolized in an organism. T1/2 is about 2 h, at newborns - is 3-4 times more, than at adults. The ceftazidime is removed in not changed look by kidneys by glomerular filtering. About 80-90% of a dose are allocated with kidneys during 24 h. Less than 1% of drug are removed with bile.

Pharmacokinetics in special clinical cases

At a renal failure the speed of removal of a ceftazidime decreases. At a hemodialysis of T1/2 makes 3-5 h.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:

— heavy infections, including intrahospital (a septicaemia, bacteremia, peritonitis, meningitis, infections at patients with reduced immunity infected burns);

— infections of urinary tract (acute and chronic pyelonephritis, pyelitis, prostatitis, cystitis, urethritis / only bacterial/, kidney abscess);

— lower respiratory tract infections (acute and chronic bronchitis, the infected bronchiectasias, the pneumonia caused by gram-negative bacteria, abscess of lungs, an empyema of a pleura, an infection of lungs in patients with a mucoviscidosis);

— infections of skin and soft tissues (mastitis, wound fevers, skin ulcers, phlegmon, ugly face);

— infections of bones and joints (septic arthritis, osteomyelitis, bacterial bursitis);

— infections of a GIT, abdominal cavity and bilious ways (coloenteritis, retroperitoneal abscesses, diverticulitis, inflammation of bodies of a small pelvis, cholecystitis, cholangitis, empyema of a gall bladder);

— infections of bodies of a small pelvis and female generative organs;

— gonorrhea (especially at hypersensitivity to antibacterial drugs from group of penicillin);

— infections of an ear, throat, nose (average otitis, sinusitis, mastoiditis).

Route of administration and doses:

The drug Tseftazidim-AKOS is used only parenterally: in/in (struyno or kapelno) or in oil. The dose of drug is established individually, taking into account weight of a course of a disease, localization of an infection, a look and sensitivity of the activator, age and function of kidneys.

The drug is administered in/in (struyno or kapelno) or an upper outside quadrant of a big gluteus, deeply in oil in area, or to the area of a lateral part of a hip. Solution of a ceftazidime can be entered directly into a vein or into a tube of infusional system.

The usual dose for adults and children is more senior than 12 years makes 1 in oil or in/in each 8-12 h.

At uncomplicated infections of urinary tract - in oil or in/in on 250 mg each 12 h.

At the complicated infections of urinary tract - in oil or in/in on 0.5-1 g each 8-12 h.

At uncomplicated pneumonia, infections of skin and soft tissues - in oil or in/in on 0.5-1 g each 8 h.

At the mucoviscidosis, respiratory infections caused by Pseudomonas spp. - in/in in a dose of 100-150 mg/kg/, frequency rate of introduction - 3 (use of a dose to 9 g / did not cause complications in such patients).

At infections of bones and joints - in/in on 2 g each 12 h.

At heavy infections, including intrahospital - in/in on 2 g each 8 h.

At extremely heavy or zhizneugrozhayushchy infections - in/in on 2 g each 8 h.

To patients of advanced age the maximum daily dose should not exceed 3 g.

Patients with a renal failure need a dose decline since the ceftazidime is removed by kidneys in not changed look. The initial dose makes 1 g. The maintenance dose is selected depending on the speed of glomerular filtering.
 
         Clearance of creatinine                                           Dose
> 50 ml/min. (> 0.83 ml/sec.)                    the Usual dose for adults
                                                                      and 12 years are more senior than children
35-50 ml/min.
(0.52-0.83 ml/sec.)                                         on 1 g each 12 h
16-30 ml/min.
(0.27-0.5 ml/sec.)                                           on 1 g each 24 h
6-15 ml/min.
(0.1-0.25 ml/sec.)                                        on 500 mg each 24 h
<5 ml/min. (<0.08 ml/sec.)                          on 500 mg each 48 h
The patients who are
 on a hemodialysis                                 on 1 g after each session of a hemodialysis
The patients who are
on peritoneal dialysis                         on 500 mg each 24 h

Patients with heavy infections can increase a maintenance dose by 50% or to increase the frequency of administration of drug. In this case it is necessary to control ceftazidime level in blood serum, serumal concentration of a ceftazidime at the same time should not exceed 40 mg/l.

For children the clearance of creatinine is calculated according to the ideal mass or surface area of a body.

Drug T1/2 during a hemodialysis makes 3-5 h. The corresponding dose of drug should be repeated after every period of dialysis.

At peritoneal dialysis the ceftazidime can be included in dialysis solution in a dose from 125 mg to 250 mg on 2 l of dialysis solution.

At the patients with a renal failure who are on a continuous hemodialysis with use of the arteriovenous shunt and at the patients who are on haemo filtering of high speed in intensive care unit, the recommended doses - 1 g / daily (in 1 or several introductions).

At the patients who are on haemo filtering of low speed appoint the doses recommended at a renal failure.

To children aged up to 2 months appoint 25-60 mg/kg/days (in 2 introductions).

To children from 2 months to 12 years appoint 30-100 mg/kg/days (in 2-3 introductions).

To children with reduced immunity, a mucoviscidosis and meningitis - 150 mg/kg/days (in 3 introductions).

The maximum daily dose of a ceftazidime for children makes 6 g.

Treatment duration

Treatment duration a ceftazidime makes 7-14 days. At the infections caused by Pseudomonas aeruginosa (pneumonia, a mucoviscidosis, meningitis), the course of treatment can be increased up to 21 days.

Rules of preparation of solutions

At dissolution of powder carbon dioxide (carbon dioxide) is emitted. After administration of solvent the bottle needs to be stirred up that transparent solution turned out. At the received ready solution of drug there can be small vials of carbon dioxide (carbon dioxide).

The received solution can have color from light yellow to dark yellow. If all recommended rules of cultivation of drug are followed, then its efficiency does not depend on a shade.

Primary cultivation
Dose                                       Volume                                                                Volume
                                          rastoritel                                                       of a rastoritel
                                      for introduction in oil                                                 for in/in introductions
500                mg 1.5 ml of water for injections                                                      of 5 ml
                  or 0.5% or 1% of solution of lidocaine of a hydrochloride         of water for injections
1 g or 2               g 3 ml of water for injections                                                  of 10 ml
                 or 0.5% or 1% of solution of lidocaine of a hydrochloride          of water for injections

Secondary cultivation

For in/in drop introductions in addition dissolve the drug Tseftazidim-AKOS solution received in the above described way in 50-100 ml of one of the following solvents intended for in/in introductions (0.9% chloride sodium solution, Ringer's solution, 5% or 10% solution of a dextrose (glucose), 5% solution of a dextrose (glucose) from 0.9% chloride sodium solution. For secondary cultivation it is necessary to use only freshly cooked solution.

Features of use:

The patients having allergic reactions to penicillin in the anamnesis can have hypersensitivity to tsefalosporinovy antibiotics.

During treatment it is impossible to use ethanol.

At use of drug and in 2-3 weeks after the termination of treatment development of the diarrhea caused by Clostridium difficile is possible. In mild cases there are enough cancellations of treatment and use of ion-exchange resins (Colestyraminum, колестипол), in hard cases compensation of loss of liquid, electrolytes and protein, purpose of Vancomycinum, bacitracin or metronidazole is shown. It is impossible to apply the medicines braking an intestines peristaltics.

Influence on ability to driving of motor transport and to control of mechanisms

During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions because of risk of developing of dizziness.

Side effects:

Allergic reactions: small tortoiseshell, fever or fever, rash, itch, bronchospasm, eosinophilia, Stephens-Johnson's syndrome, toxic epidermal necrolysis (Lyell's disease), Quincke's disease, acute anaphylaxis.

From the alimentary system: nausea, vomiting, diarrhea, meteorism, abdominal pain, dysbacteriosis, increase in activity of hepatic transaminases, ShchF, hyperbilirubinemia, stomatitis, glossitis, pseudomembranous coloenteritis, orofaringealny candidiasis, cholestasia.

From system of a hemopoiesis: eosinophilia, leukopenia, neutropenia, agranulocytosis, granulocytopenia, thrombocytopenia, hemolitic anemia, lymphocytosis, hemorrhages.

From a reproductive system: mycotic vulvovaginitis.

From an urinary system: renal failure, toxic nephropathy.

From TsNS: a headache, dizziness, paresthesias, dizziness, convulsive attacks, encephalopathy, "the flitting tremor".

Laboratory indicators: giperkreatininemiya, increase in concentration of urea, false positive reaction of urine to glucose, false positive forward reaction of Koombs, increase in a prothrombin time.

Local reactions: at in introduction - phlebitis; at introduction in oil - morbidity, burning, consolidation in the place of an injection.

Others: nasal bleedings, superinfection.

Interaction with other medicines:

Synergism of antibacterial action at simultaneous use with aminoglycosides is noted.

"Loopback" diuretics, aminoglycosides, Vancomycinum, clindamycin reduce clearance of a ceftazidime therefore the risk of nephrotoxic action increases.

Bacteriostatic antibiotics (including chloramphenicol) reduce effect of drug.

Pharmaceutical interaction

It is impossible to use Natrii hydrocarbonas solution as solvent (carbon dioxide is formed, it can demand production of gas outside).

Pharmaceutical it is incompatible with aminoglycosides (a considerable mutual inactivation: at simultaneous use these drugs should be administered in different body parts) and Vancomycinum (forms a deposit depending on concentration; if necessary to administer two drugs through one tube, between their use systems for in/in introductions should be washed out).

Pharmaceutical we will combine with the following solutions: at concentration from 1 to 40 mg/ml – sodium chloride of 0.9%, sodium a lactate, Hartman's solution, dextrose (glucose) of 5%, sodium chloride of 0.225% and dextrose (glucose) of 5%, sodium chloride of 0.45% and dextrose (glucose) of 5%, sodium chloride of 0.9% and dextrose (glucose) of 5%, sodium chloride of 0.18% and dextrose (glucose) of 4%, dextrose (glucose) of 10%, a dextran 40 (10%) in solution of sodium of chloride of 0.9%, a dextran 40 (10%) in solution of a dextrose (glucose) of 5%, a dextran 70 (6%) in solution of sodium of chloride of 0.9%, a dextran 70 (6%) in solution of a dextrose (glucose) of 5%.

At concentration from 0.05 to 0.25 mg/ml the ceftazidime is compatible to solution for intraperitoneal dialysis (lactate).

For introduction in oil the ceftazidime can be divorced with solution of lidocaine of a hydrochloride of 0.5% or 1%. Both components keep activity if the ceftazidime is added to the following solutions (concentration of a ceftazidime of 4 mg/ml): a hydrocortisone, (a sodium hydrocortisone phosphate) 1 mg/ml in solution of sodium of chloride of 0.9% or solution of a dextrose (glucose) of 5%, tsefuroksy (tsefuroksy sodium) 3 mg/ml in solution of sodium of chloride of 0.9%, клоксациллин (клоксациллин sodium) 4 mg/ml in solution of sodium of chloride of 0.9%, heparin of 10 ME/ml in solution of sodium of chloride of 0.9%, potassium chloride 10 ¼Ý¬ó/l or 40 ¼Ý¬ó/l in solution of sodium of chloride of 0.9%.

At ceftazidime solution mixing (500 mg in 1.5 ml of water for injections) and metronidazole (500 mg / 100 ml) both components keep the activity.

Contraindications:

— hypersensitivity to drug components;

— hypersensitivity to cephalosporins and penicillin.

With care: a renal failure, colitis in the anamnesis, a sprue (the risk of decrease in prothrombin activity, especially at persons with the expressed renal and/or liver failure is increased), simultaneous introduction with "loopback" diuretic and aminoglycoside, and also the newborn.

 

Use of drug TSEFTAZIDIM-AKOS at pregnancy and feeding by a breast
At pregnancy drug is used only if the estimated advantage for mother exceeds potential risk for a fruit and the child. At use of drug in the period of a lactation feeding by a breast should be stopped.

 

Use at abnormal liver functions
With care it is necessary to appoint drug at patients with an abnormal liver function.

 

Use at renal failures
Patients with a renal failure need a dose decline since the ceftazidime is removed by kidneys in an invariable look. The initial dose makes 1 g. The maintenance dose is selected depending on the speed of glomerular filtering.

                   KK                                                                         Dose
> 50 ml/min. (> 0.83 ml/sec.)                              the Usual dose for adults and children
                                                                                          12 years are more senior
35-50 ml/min. (0.52-0.83 ml/sec.)                                 on 1 g each 12 h
16-30 ml/min. (0.27-0.5 ml/sec.)                                   on 1 g each 24 h
6-15 ml/min. (0.1-0.25 ml/sec.)                                   on 500 mg each 24 h
<5 ml/min. (<0.08 ml/sec.)                                          on 500 mg each 48 h
The patients who are on a hemodialysis      on 1 g after each session of a hemodialysis
The patients who are on
peritoneal dialysis                                          on 500 mg each 24 h

Patients with heavy infections can increase a maintenance dose by 50% or to increase the frequency of administration of drug. In this case it is necessary to control ceftazidime level in blood serum, serumal concentration of a ceftazidime at the same time should not exceed 40 mg/l.

For children the clearance of creatinine is calculated according to the ideal mass or surface area of a body.

Drug T1/2 during a hemodialysis makes 3-5 h. The corresponding dose of drug should be repeated after every period of dialysis.

At peritoneal dialysis the ceftazidime can be included in dialysis solution in a dose from 125 mg to 250 mg on 2 l of dialysis solution. At the patients with a renal failure who are on a continuous hemodialysis with use of the arteriovenous shunt and at the patients who are on haemo filtering of high speed in intensive care unit, the recommended doses - 1 g / daily (for one or several introductions).

At the patients who are on haemo filtering of low speed appoint the doses recommended прн a renal failure.

 

Use for elderly patients

To patients of advanced age the maximum daily dose should not exceed 3 g.

 

Use for children

To children aged up to 2 months appoint 25-60 mg/kg/days (in 2 introductions).

To children from 2 months to 12 years appoint 30-100 mg/kg/days (in 2-3 introductions).

To children with reduced immunity, a mucoviscidosis and meningitis - 150 mg/kg/days (in 3 introductions).

The maximum daily dose for children makes 6 g.

Overdose:

Symptoms: pain, an inflammation, phlebitis in the place of an injection, dizziness, paresthesias, a headache, spasms at patients with a renal failure, a giperkreatininemiya, a hyperbilirubinemia, a thrombocytosis, thrombocytopenia, an eosinophilia, a leukopenia, lengthening of a prothrombin time.

Treatment: carry out symptomatic therapy, in case of a renal failure - peritoneal dialysis or a hemodialysis.

Storage conditions:

Drug should be stored in the unavailable to children, dry, protected from light place at a temperature not above 25 °C. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Bottles with a capacity of 10 ml (1) - packs cardboard.
Bottles with a capacity of 10 ml (50) - boxes cardboard.
Bottles with a capacity of 20 ml (1) - packs cardboard.
Bottles with a capacity of 20 ml (50) - boxes cardboard.