Вицеф®

General characteristics. Structure:

Active ingredient: 0,5 g, 1,0 g and 2,0 g of a ceftazidime of pentahydrate (in terms of tsevtazidy).
Excipient: sodium carbonate.
 
Antibacterial drug from group of cephalosporins III of generation.

Pharmacological properties:

Pharmacodynamics. The ceftazidime is antibacterial drug from group of cephalosporins III of generation, possesses a wide range and works bakteritsidno, breaking the final stages of synthesis of a cell wall of bacteria due to irreversible linkng with transpeptidases (penicillin - the connecting proteins); it is steady against action of the majority beta лактамаз. Affects many strains steady against ampicillin and other cephalosporins.

It 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), Steptococcus pyogenes (group A a beta and hemolitic streptococcus), Streptococcus agalactiae (group B), Streptococcus pneumoniae; anaerobic bacteria: Bacteroides spp. (majority of strains of Bacteroides fragilis of a rezistentna).

In researches in vitro against the majority of strains is active: Acinetobacter spp., Haemophilus parainfluenzae, Morganella morganii, Neisseria gonorrhoeae, Providencia spp., Providencia rettgeri, Salmonella spp., Shigella spp., Staphylococcus epidermidis, Yersinia enterocolitica, Clostridium perfringens, excepting Clostridium difficile, Peptococcus spp., Peptostreptococcus spp.

The ceftazidime is inactive concerning steady against Staphylococcus spp Methicillinum., Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes, Campylobacter spp. and Clostridium difficile.

Pharmacokinetics. After intravenous (in/in) bolyusny introductions of 0,5 g and 1 g of a ceftazidime average values of the maximum serumal concentration - 42 mg/l and 90 mg/l, respectively. After intramuscular introduction of 0,5 g (in oil) or 1 g the maximum serumal concentration making, on average, 17 mg/ml and 39 mg/l, respectively, are reached in 1 hour after introduction. Therapeutic significant concentration in a blood plasma remain during 8-12 h.

Later in/in or introductions in oil the ceftazidime is quickly distributed in a human body. The concentration of an antibiotic exceeding MPK for sensitive microorganisms are reached in the majority of fabrics and liquids, including synovial, intraocular, pericardiac and peritoneal liquids, bile, a phlegm, I wet, a bone tissue, a myocardium, a gall bladder, skin and soft tissues; diffusion of drug increases at inflammatory processes.

Badly gets through not changed brain covers. At meningitis permeability through a blood-brain barrier increases, at the same time in cerebrospinal fluid the therapeutic concentration making 4-20 mg/l and above are reached. Passes through a placenta; in low concentration gets into breast milk. Reversibly contacts proteins of plasma (less than 10%). Extent of binding does not depend on concentration of an antibiotic. The ceftazidime does not force out bilirubin from complexes with proteins of plasma. The volume of distribution makes 0,21 - 0,28 l/kg.

It is removed by kidneys (90% of the entered dose in an invariable look within 24 hours) by glomerular filtering and canalicular secretion. Adults with normal function of kidneys have an elimination half-life from blood serum - 1,9 h.

At newborns, especially premature, the ceftazidime elimination half-life from serum can exceed by 3-4 times a similar indicator at adults. The elimination half-life from fabrics is more, than from blood serum.

At patients with a renal failure the elimination half-life increases that demands correction of doses and modes of introduction (if clearance of creatinine less than 50 ml/min.).

Less than 1% of drug are allocated with bile. Drug is not metabolized in a liver, the abnormal liver function is not reflected in drug pharmacokinetics. The dose at such patients remains usual.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to a ceftazidime:
- infections of the central nervous system (bacterial meningitis and abscess of a brain);
- infections of ENT organs (average otitis, malignant inflammation of an outside ear, mastoiditis, sinusitis, etc.);
- lower respiratory tract infections (bronchitis, the infected bronchiectasias, pneumonia, abscess of lungs, an empyema of a pleura, an infection of lungs at patients with a mucoviscidosis);
- infections of abdominal organs and biliary tract (cholangitis, cholecystitis, empyema of a gall bladder, retroperitoneal abscesses, peritonitis, diverticulitis);
- digestive tract infections (coloenteritis);
- infections of skin and soft tissues, wound and burn fevers;
- infections of bones and joints (osteomyelitis, septic arthritis);
- infections of kidneys and urinary tract (pyelonephritis, a pyelitis, kidney abscess, prostatitis, cystitis, an urethritis, infections of kidneys at patients with an urolithiasis);
- infectious and inflammatory diseases of bodies of a small pelvis at women (an endometritis, a pelviperitonitis, a salpingitis, a parametritis, pelvic cellulitis);
- sepsis;
- the infections connected by dialysis;
- prevention of infectious complications at prostate gland operations.

Route of administration and doses:

Вицеф® it is entered parenterally - in/in and in oil.
At adults and children 12 years a usual single dose of Vitsefa® are more senior makes 1 g each 8-12 hours or on 2 g with an interval of 12 h.

Also following doses, frequency rate and ways of introduction which are defined by localization and disease severity are recommended:
- at uncomplicated infections of urinary tract - on 0,25 g each 12 hours in/in or in oil;
- at the complicated infections of urinary tract - on 0,5 g each 8 or 12 hours in/in or in oil;
- at uncomplicated pneumonia, infections of skin and soft tissues, infections of ENT organs - on 0,5-1 g each 8 hours in/in or in oil;
- at heavy intraabdominal or gynecologic infections - on 2 g each 8 hours in/in;
- at infections of bones and joints - on 2 g each 12 hours in/in;
- at bacterial meningitis - on 2 g each 8 hours in/in;
- at heavy, life-threatening infections and a febrile neutropenia - on 2 g each 8 hours in/in, or to 3 g are each 12 hours in/in (the maximum daily dose - 6 g);
- at the heavy pulmonary infection caused by Pseudomonas aeruginosa patients with a mucoviscidosis and normal function of kidneys - to 30-50 mg/kg have each 8 hours in / century.

For an antibiotikoprofilaktika of postoperative complications at prostate gland operations in 30 min. prior to operation enter into 1 g of Vitsefa®, during removal of an uric catheter it is recommended to enter 1 g of Vitsefa® repeatedly.

To children is more senior 1 month and up to 12 years usually enter 30-50 mg/kg each 8 hours.

For therapy of bacterial meningitis, and also treatment of infections at children with an immunodeficiency or a mucoviscidosis, the daily dose makes 150 mg/kg (but not higher than 6 g a day) which is divided into 3 introductions.

The newborn (to children up to 1 month) appoint 30 mg/kg each 12 hours in / century.

Dose adjustment and the introduction modes, proceeding from indicators of clearance of creatinine is required from patients with renal failures. Treatment begin with introduction 1 g of Vitsefa® as the first, load dose. Further the supporting mode is calculated how it is presented in the table:

KK, ml/min.	50-31	30-16	15-5	<5
Mode	1 g each 12 h	1 g each 24 h	0,5 g each 24 h	0,5 g each 48 h

Patients with infections of a heavy current against the background of a chronic renal failure can increase the single doses specified in the table (see above) by 50%, or to reduce intervals between introductions. Further, correction of the mode of dosing is carried out on the basis of the allocated microorganisms given to sensitivity, by weights of a condition of the patient and data of therapeutic monitoring of concentration of a ceftazidime in blood serum (residual concentration should not exceed 40 mg/l).

At a hemodialysis: a load dose - 1 g, then on 1 g after each procedure of a hemodialysis. At a continuous hemodialysis with use of the arteriovenous shunt and when carrying out high-speed haemo filtering - 1 g/days daily (for one or several introductions). When carrying out haemo filtering with a low speed ^{of Vitsef®} appoint in the doses recommended at a renal failure (see the table above).

At peritoneal dialysis enter 1 g (a load dose) in the beginning, then appoint 0,5 g each 24 hours. In addition to in/in or to introduction in oil, introduction ^{of Vitsefa®} as a part of dialysis solution at the rate of 0,25 g ^{of Vitsefa®} on 2 l of dialysis solution is possible.

Vitsef's introduction should be continued within 2 days after disappearance of symptoms of an infection. In hard cases and the complicated infections long courses of treatment can be required.

^Вицеф® enter intravenously (struyno, kapelno) and intramusculary.
Dissolution ^{of Vitsefa®} is followed by insignificant exothermic reaction at which carbon dioxide is released and in a bottle positive pressure is created. Vials of carbon dioxide can be present at ready solution that does not influence efficiency of drug. Easy yellowing of solution also does not influence efficiency.

Intramuscular introduction. For introduction in oil the sterile ^{powder Vitsefa®} is dissolved in sterile water for injections or 0,5-1% hydrochloride lidocaine solution (in the absence of instructions on intolerance of local anesthetics of amide type).

The following minimum quantities of solvent add directly to a bottle with dry powder of an antibiotic:

 

in the bottle containing 0,5 g of Vitsefa®	1,5 ml
in the bottle containing 1,0 g of Vitsefa®	3,0 ml

The received solution, approximate concentration of a ceftazidime in which 260 mg/ml, enter deeply intramusculary into body parts with the expressed muscular layer (an upper outside quadrant of a buttock or the lateral surface of a hip). It is recommended to carry out the test for aspiration to avoid undesirable administration of solution in a blood vessel.

Intravenous administration. For in/in jet introductions ^{of Vitsef®} dissolve in sterile water for injections. The following amounts of solvent add directly to a bottle with dry powder of an antibiotic:

 

	in the bottle containing 0,5 g of Vitsefa®	5,0 ml
	in the bottle containing 1,0 g of Vitsefa®	10 ml
	in the bottle containing 2,0 g of Vitsefa®	20 ml

The received solution, approximate concentration of a ceftazidime in which 90 mg/ml, enter in/in slowly, within 3-5 min.; introduction through a special node or port for system injections for in/in infusions is possible if the patient receives liquids, compatible to ^Vitsefom®, parenterally. 
For in/in drop introductions of Vitsef® dissolve, as for in/in jet introductions (see above). The received solution is added to the bottle containing 50-100 ml of the compatible infusional environment. Enter through system for in/in infusions within not less than 30 minutes. Вицеф® it is compatible from 5% solution of a dextrose, 0,9% solution of sodium of chloride, 10% the dextrose solution, aqueous solution containing 0,225% of sodium of chloride and 5% of a dextrose; the aqueous solution containing 0,45% of sodium of chloride and 5% of a dextrose; the aqueous solution containing 0,9% of sodium of chloride and 5% of a dextrose; Ringer's solution; laktirovanny solution of Ringer; 1/6 M lactate sodium solution; 10% solution of invert sugar; Normozol-M solution from 5% glucose.

Features of use:

At intramuscular introduction patients with intolerance of local anesthetics of amide type cannot use as solvent 0,5% or 1% lidocaine solution.

When developing diarrhea during treatment of Vitsefom® it is necessary to show vigilance in view of possible development of pseudomembranous colitis. If the diagnosis an antibiotic - the associated diarrhea or pseudomembranous colitis is established, it is necessary to stop immediately introduction of Vitsefa® and to appoint the corresponding treatment.

As well as in case of use of other antibiotics, use of Vitsefa® can lead to colonization of insensitive microflora and development of superinfection.

When determining glucose in urine by Benedict or Felinga's method, and also with use of Klinitesta® false positive results can seldom be observed.

Researches about influence of a ceftazidime on performance of potentially dangerous types of activity requiring special attention and speed of reactions were not conducted.

Considering possible development of dizziness, at use of a ceftazidime it is necessary to be careful during the driving of vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Allergic reactions: in 2% and less - makulopapulezny rash, an itch, fever; very seldom - a Quincke's disease, a polymorphic erythema, Stephens-Johnson's syndrome and a toxic epidermal necrolysis.

From the alimentary system: in 2% and less - diarrhea, nausea, vomiting, an abdominal pain, colitis, a cholestasia; very seldom - jaundice, the pseudomembranous colitis connected with Clostridium difficile.

From a nervous system: in 1% and less - dizziness, a headache; paresthesias; very seldom - convulsive attacks. It was reported about cases of neurologic complications, such as a tremor, a myoclonia, spasms, encephalopathy and a coma at patients with a renal failure for which the dose of a ceftazidime was not respectively reduced.

From bodies of a hemopoiesis: in 2% and less - an eosinophilia, a thrombocytosis; very seldom - a tranzitorny leukopenia, a neutropenia, thrombocytopenia, a lymphocytosis, hemolitic anemia and an agranulocytosis.

From an urinary system: very seldom - intersticial nephrite, a renal failure, a renal failure.

From laboratory indicators: in 2% and less - tranzitorny increase in activity of "hepatic" transaminases (nuclear heating plant, ALT), an alkaline phosphatase, LDG, false positive forward reaction of Koombs without hemolysis; less, than in 1% - a tranzitorny giperkreatininemiya, increase in level of urea and/or creatinine of plasma.

Local reactions: in 2% and less - pain and/or an inflammation in the place in/in an injection; at introduction in oil - morbidity and consolidation in an injection site.
Others: less, than in 1% - fever, candidiasis of an oral cavity and a mycotic vulvovaginitis.

Interaction with other medicines:

At co-administration of Vitsefa® with aminoglycosides sinergidny and additive effects are observed.

In solution pharmaceutical it is incompatible with aminoglycosides (a considerable mutual inactivation: at simultaneous use) and Vancomycinum (forms a deposit depending on concentration). At simultaneous use it is not necessary to mix them in one syringe or one infusional environment; at introduction in oil to enter into different body parts; at intravenous administration it is recommended to enter separately, observing a certain sequence with a time interval between injections (infusions), or to use separate in/in catheters.

It is impossible to use Natrii hydrocarbonas solution as solvent.

At simultaneous use of cephalosporins with loopback diuretics and aminoglycosides the risk of nephrotoxicity increases.

Chloramphenicol and beta лактамные antibiotics, including a ceftazidime, work antagonistically therefore it is necessary to avoid their simultaneous use.

The ceftazidime solution in concentration of 4 mg/ml prepared with use of 5% of solution of a dextrose or 0,9% of solution of sodium of chloride we will combine 3 mg/ml with solution of a tsefuroksim of sodium; solution of heparin of 10 ME/ml and 50 ME/ml, chloride 10 potassium solution ¼Ø¬/l and 40 ¼Ø¬/l.

When mixing Vitsefa® solution in concentration of 20 mg/ml and metronidazole of 5 mg/ml both components keep the activity.

In concentration from 0,05 to 0,25 mg/ml the ceftazidime is compatible to solution for peritoneal dialysis (lactate).

Contraindications:

Hypersensitivity to a ceftazidime, other cephalosporins and penicillin.

With care appoint at instructions in the anamnesis to colitis; a sprue (the risk of decrease in prothrombin activity is increased); the neonatality period, a renal failure, in a combination with loopback diuretics and aminoglycosides.

There are no data confirming embriotoksichesky or teratogenic action of a ceftazidime, however during pregnancy (the I trimester) is used only according to strict indications, at confidence that the potential advantage of use for mother exceeds possible risk for a fruit.
The ceftazidime in small concentration gets into breast milk therefore in need of use in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

The overdose of a ceftazidime was observed at patients with a renal failure.
Symptoms: increase in convulsive activity, the "flitting" tremor, encephalopathy, neuromuscular irritability, a coma.
Treatment: symptomatic and maintenance therapy. In case of heavy overdose concentration of drug in blood can be reduced by means of a hemodialysis.

Storage conditions:

List B. In dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C.
Freshly cooked solution of drug is good for use within 18 hours at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

0,5 g and 1,0 g of active agent in bottles glass with a capacity of 10 ml;

2,0 g of active agent in bottles glass with a capacity of 20 ml.

Solvent - "Water for injections" in glass ampoules of 5 ml.

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

1 bottle with drug and 1 ampoule with solvent is packed into a blister strip packaging. One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug pack into blister strip packagings. One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug complete with 5 ampoules of solvent pack into blister strip packagings. One blister strip packaging with drug, one blister strip packaging with solvent and the application instruction is put in a pack cardboard.