Tseftazidim-Dzhodas

General characteristics. Structure:

Active ingredient: 1 g of a tseftazidin in the form of a ceftazidime pentahydrate.

Excipient: sodium carbonate.

Pharmacological properties:

Pharmacodynamics. The ceftazidime is a tsefalosporinovy antibiotic of the III generation for parenteral use. Works bakteritsidno (breaks synthesis of a cell wall of microorganisms). Possesses a broad spectrum of activity. It is steady against action of the majority beta лактамаз. Affects many strains steady against ampicillin, etc. to cephalosporins.

Drug is active concerning gram-negative microorganisms: Pseudomonas spp., (the ceftazidime has the highest activity among generation cephalosporins III concerning Pseudomonas aeruginosa), Klebsiella spp., including Klebsiella pneumoniae, Proteus mirabilis (including indolpositive), Proteus vulgaris and other Proteus spp., Escherichia coli, Enterobacter spp., including Enterobacter aerogenes, Enterobacter cloacae, Citrobacter spp., including Citrobacter diversus, Citrobacter freundii, Pasteurella multocida, Neisseria meningitides, Haemophillus influenzae (including the strains steady against ampicillin).

Drug is active concerning 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.

Drug is active concerning anaerobic bacteria: Bacteroides spp. (the majority of strains of Bacterioides fragilis - a rezistentna).

Drug is not active concerning metitsillinustoychivy strains of Staphylococcus spp., Streptococcus faecalis., Enterococcus spp. Listeria monocytogenes., Campilobacter spp., Clostridium difficile.

Drug is active in vitro against the majority of strains of the following microorganisms: Clostridium perfringens, not including Clostridium difficile, Acinetobacter spp., Haemophilus parainfluenzae, Morganella morganii, Neisseria gonorrhoeae, Peptococcus spp., Peptostreptococcus spp., Providencia rettgeri, Salmonella spp., Shigella spp., Staphylococcus epidermidis, Yersinia enterocolitica.

Pharmacokinetics. After introduction drug is quickly distributed in a human body and reaches therapeutic concentration in the majority of fabrics and liquids, including synovial, pericardiac and peritoneal fluid, and also in bile, a phlegm and urine. Distribution also happens in bones, a myocardium, a gall bladder, skin and soft tissues. Badly gets through the unimpaired blood-brain barrier, but the therapeutic level reached by drug in cerebrospinal fluid is sufficient for treatment of meningitis (4-20 mg/l and above). Easily gets through a placenta and it is allocated with breast milk.

Communication with proteins of plasma - less than 10%. The maximum concentration at intramuscular introduction of 0,5 g or 1 g in an hour (time of achievement of the maximum concentration in plasma) respectively makes 17 mkg/ml and 39 mkg/ml, at intravenous administration of 0,5 g, 1 g or 2 g respectively 42 mkg/ml and 69 mkg/ml and 170 mg/l.

Time of achievement of the maximum concentration at intramuscular introduction - 1 h, at intravenous administration - by the end of infusion. Concentration of drug, equal 4 mkg/ml remains during 6 - 8 h. Therapeutic concentration in a blood plasma remains during 8 - 12 h later in/in and introductions in oil.

Elimination half-life at normal renal function - 1,9 h; at newborns - is 3-4 times more long; at a hemodialysis - 3-5 h.

Drug is not metabolized in a liver, the abnormal liver function is not reflected in a pharmacodynamics and pharmacokinetics of drug. The dose at such patients remains usual.

It is removed in not changed look by kidneys to 80-90% (70% of the entered dose are removed in the first 4 h) within a day by glomerular filtering; with bile – less than 1%. At a renal failure the dose decline is recommended.

Indications to use:

• The infectious and inflammatory diseases caused by microorganisms, sensitive to drug.
• Heavy infections: peritonitis, sepsis (septicaemia), heavy it is purulent - septic states, meningitis.
• Lower respiratory tract infections: pneumonia, lung abscess, the pleura empyema infected a bronchietasia, bronchitis.
• Infections of ENT organs: average otitis, mastoiditis, sinusitis, etc.
• Infections of urinary tract: pyelonephritis, pyelitis, prostatitis, cystitis, urethritis, kidney abscess.
• Infections of bones and joints: septic arthritis, osteomyelitis, bacterial bursitis.
• Infections of skin and soft tissues: the wound fevers infected burns, phlegmon, an ugly face, mastitis.
• Infections of digestive tract, abdominal cavity and bilious ways: retroperitoneal abscesses, cholangitis,
empyema of a gall bladder, cholecystitis, peritonitis, diverticulitis, coloenteritis.
• Infections of female generative organs: endometritis.
• Gonorrhea (especially at hypersensitivity to antibiotics of a penicillinic row).

Route of administration and doses:

Drug is appointed intravenously or intramusculary. The dose of drug is established individually, taking into account weight of a course of a disease, localization of an infection and sensitivity of the activator, age and body weight, function of kidneys.

The usual dose for adults and children is more senior than 12 years. At extremely heavy infections: intravenously on 2 g each 8 h.

At a mucoviscidosis, infections of the lungs caused by Pseudomonas spp.: from 100 to 150 mg/kg/days, frequency rate of introduction - 3 times in days.

At the complicated infections of urinary tract: on 500 mg - 1 g each 8-12 h.

At uncomplicated pneumonia and infections of skin: on 500 mg - 1 g each 8 h.

At infections of bones and joints: intravenously on 2 g each 12 h.

After an initial dose of 1 g, adult with a renal failure (including patients to whom carry out dialysis), the dose decline can be required, as shown below.

Clearance of creatinine: 35 - 50 ml/min. - a dose: on 1 g each 12 h; 15 - 30 ml/min. - on 1 g each 24 h; 5 - 15 ml/min. - on 500 mg each 24 h; <5 ml/min. - on 500 mg each 48 h; patients to whom carry out a hemodialysis - on 1 g after each session of a hemodialysis; patients to whom carry out peritoneal dialysis - on 500 mg each 24 h.

These indicators approximate. At such patients it is recommended to control drug level in serum which should not exceed 40 mg/l.

The drug elimination half-life during a hemodialysis makes 3 - 5 h. The corresponding dose of drug should be repeated after each session of dialysis.

At peritoneal dialysis drug can be included in dialysis liquid in a dose from 125 mg to 250 mg on 2 l of dialysis liquid.

Usual dose for children. Children aged up to 2 months: intravenous infusion, 30 mg/kg/days, frequency rate of introduction of 2 times/days. Children from 2 months to 12 years: intravenous infusion, 30 - 50 mg/kg/days, frequency rate of introduction of 3 times/days. To children with reduced immunity, a mucoviscidosis, meningitis each 12 h appoint a dose to 150 mg/kg/days. The maximum daily dose for adults and children should not exceed 6 g.

Preparation of solutions.    

1. "Primary" cultivation: 0,25 g + 1 ml of water for injections at intramuscular introduction or 2,5 ml of water for injections at intravenous administration; 0,5 g + 1,5 ml of water for injections at intramuscular introduction or 5 ml of water for injections at intravenous administration; 1,0 g + 3 ml of water for injections at intramuscular introduction or 10 ml of water for injections at intravenous administration.

2. "Secondary" cultivation: for intravenous drop administration the drug solution received in the above described way is in addition dissolved in 50 - 100 ml of one of the following solvents intended for intravenous administration: • 0,9% chloride sodium solution; • Ringer's solution; • 5%, 10% solution of glucose (dextrose); • 5% solution of glucose (dextrose) from 0,9% chloride sodium solution.

To use only freshly cooked solution!

Features of use:

Use at pregnancy and in the period of a lactation. Use at pregnancy is possible only when the estimated advantage for mother exceeds potential risk for a fruit. In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

At 3-7% of patients with an allergy to penicillin in the anamnesis cross hypersensitivity to cephalosporins is noted.

The ceftazidime can interfere with synthesis of vitamin K owing to suppression of an indestinal flora that can cause decrease in level of blood-coagulation factors, dependent on vitamin K, and in rare instances lead to a gipotrombinemiya and bleeding. Purpose of vitamin K quickly eliminates a gipotrombinemiya. At the elderly and weakened patients, at patients with an abnormal liver function and at persons with defective food the risk of development of bleedings is highest.

At some patients pseudomembranous colitis can develop in time or after use of a ceftazidime. In mild cases there is enough drug withdrawal, and in heavier - recovery of water-salt and proteinaceous balance is recommended. If these measures do not help, appoint metronidazole, bacitracin or Vancomycinum.

Positive reaction of Koombs and false positive reaction of urine to glucose is possible.

During treatment it is impossible to use ethanol.

Side effects:

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

From the alimentary system: nausea, vomiting, diarrhea or a lock, a meteorism, an abdominal pain, dysbacteriosis, an abnormal liver function (tranzitorny increase in activity of "hepatic" transaminases, an alkaline phosphatase, a giperkreatininemiya), it is rare - stomatitis, a glossitis, a pseudomembranous coloenteritis, a cholestasia.

From bodies of a hemopoiesis: leukopenia, neutropenia, granulocytopenia, thrombocytopenia, hemolitic anemia, hypocoagulation.

From an urinary system: a renal failure (an azotemia, increase in content of urea in blood), an oliguria, an anury, a toxic nephropathy.

From a nervous system: headache, dizziness.

Local reactions: phlebitis, morbidity on the vein course; morbidity and infiltrate in the place of intramuscular introduction.

Others: nasal bleedings, candidiasis, superinfection.

Interaction with other medicines:

Pharmaceutical it is incompatible with aminoglycosides, heparin, Vancomycinum.

It is impossible to use Natrii hydrocarbonas solution as solvent!

"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 we will combine with the following solutions: at concentration from 1 to 40 mg/ml - sodium chloride of 0,9%; sodium lactate; Gartman's solution; dextrose of 5%; sodium chloride of 0,225% and Dextrosum of 5%; sodium chloride of 0,45% and Dextrosum of 5%; sodium chloride of 0,9% and Dextrosum of 5%; sodium chloride of 0,18% and Dextrosum of 4%; dextrose of 10%; a dextran with a whitebait. 10% weighing 40 thousand Da in solution of sodium of chloride of 0.9% or in solution of a dextrose of 5%; a dextran with a whitebait. weighing about 70 thousand Da 6% in solution of sodium of chloride of 0,9% or in solution of a dextrose 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 in solution of a dextrose 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 or 50 ME/ml in solution of sodium of chloride of 0,9%; potassium chloride 10 ¼Ø¬/l or      40 ¼Ø¬/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, including to other cephalosporins.

With care: the expressed renal failures, pregnancy and the period of a lactation; newborns; bleedings in the anamnesis; nonspecific ulcer 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).

Overdose:

Symptoms: introduction of inadequately high doses of drug can cause dizziness, paresthesias, a headache, convulsive attacks, deviations in results of laboratory analyses.

Treatment: as the specific antidote is absent, treatment of overdose of tsefalosporinovy antibiotics symptomatic and supporting. In case of heavy overdose when conservative therapy is unsuccessful, concentration of drug in blood can be reduced by means of a hemodialysis.

Storage conditions:

Period of validity - 3 years. Not to use after the expiry date specified on packaging. To store in dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous and intramuscular administration of 1,0 g. On 1,0 g of active ingredient in the bottle of transparent glass with a capacity of 10 ml corked by a stopper from the chlorbutyl rubber which is pressed out by an aluminum cap with a safety plastic cap. On 1 bottle with drug together with the application instruction in a cardboard pack. For hospitals: On 10,20,48 and 100 bottles together with the application instruction in a cardboard box.