Bestum

General characteristics. Structure:

Active ingredient: 250 mg, 500 mg or 1000 mg of a ceftazidime of pentahydrate in terms of a ceftazidime.

Excipient: sodium carbonate.

Tsefalosporinovy antibiotic of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. The ceftazidime is antibacterial drug from group of cephalosporins III of generation, possesses a wide range and works bakteritsidno, breaks synthesis of a cell wall of microorganisms, is steady against action of the majority beta лактамаз.

Drug is active concerning gram-negative microorganisms: Haemophillus influenzae, Neisseria gonorrhoeae and other Neisseria spp. and most of representatives of the Enterobacteriaceae family (Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and other Klebsiella spp., Morganella morganii and other Morganella spp., Proteus mirabilis (including indolpositive), Proteus vulgaris and other Proteus spp., Providencia rettgeri and other Providencia spp. and Serratia spp.), Acinetobacter spp., Haemophillus parainfluenzae (including the strains steady against ampicillin), Pasteurella multocida, Salmonella spp., Shigella spp. and Yersinia enterocolitica.

The ceftazidime has the highest activity among generation cephalosporins III concerning Pseudomonas aeruginosa and an intra hospital infection. Drug is active concerning gram-positive bacteria: Micrococcus spp., Streptococcus aureus, Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pyogenes of group A, Streptococcus viridans and other Streptococcus spp. (excepting Streptococcus faecalis); strains sensitive to Methicillinum: Staphylococcus aureus, Staphylococcus epidermidis.

The ceftazidime is active concerning anaerobic bacteria: Bacteroides spp. (the majority of strains of Bacterioides fragilis - a rezistentna), Clostridium perfingens, Peptococcus spp., Peptostreptococcus spp. and Propionobacterium spp. Drug is not active concerning metitsillinustoychivy strains of Campilobacter spp., Chlamydia spp., Clostridium difficile, Enterococcus spp., Listeria monocytogenes and other Listeria spp., Staphylococcus aureus and Staphylococcus epidermidis; Streptococcus faecalis.

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 in the concentration sufficient for treatment of infectious diseases, especially at the inflammatory processes strengthening drug diffusion. Badly gets through the unimpaired blood-brain barrier, but the therapeutic level reached by drug in cerebrospinal fluid is sufficient for treatment of meningitis. Reversibly contacts proteins of plasma (less than 15%), and possesses bactericidal action only in a free look. Extent of linkng with proteins does not depend on concentration.

The maximum concentration at intramuscular introduction of 0,5 g or 1 g is respectively equal 17 mkg/ml and 39 mkg/ml, at intravenous administration respectively 42 mkg/ml and 69 mkg/ml. 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. An elimination half-life at normal renal function - 1,8 h; at broken - 2,2 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 and canalicular secretion equally. At a renal failure the dose decline is recommended. The volume of distribution makes 0,21 - 0,28 l/kg. Drug collects in soft tissues, kidneys, lungs, bones and joints, serous cavities.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to a ceftazidime:
- heavy infections: meningitis; sepsis (septicaemia); heavy it is purulent - septic states;

- infections of bones and joints: septic arthritis, osteomyelitis, bacterial bursitis;

- respiratory infections: acute and chronic bronchitis, the infected bronchietasia, pneumonia caused by gram-negative bacteria abscess of lungs, a pleura empyema;

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

- infections of skin and soft tissues: the mastitis, wound fevers, skin ulcers, phlegmon, an ugly face infected burns;

- infections of a GIT (digestive tract), abdominal cavity and bilious ways: peritonitis, coloenteritis, retroperitoneal abscesses, diverticulitis, inflammations of bodies of a small pelvis, cholecystitis, cholangitis, empyema of a gall bladder;

- infections of female generative organs;

- infections of an ear, throat, nose: average otitis, sinusitis, mastoiditis, etc.;

- gonorrhea (especially at hypersensitivity to antibacterial drugs from group of penicillin).

Route of administration and doses:

The ceftazidime is applied only parenterally. 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 the complicated infections of urinary tract intramusculary or intravenously on 500 mg - 1 g each 8-12 h;

• at uncomplicated pneumonia and infections of skin and soft tissues intramusculary or intravenously on 500 mg-1 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 a day (use of a dose to 9 g/days did not cause complications in such patients);

• at infections of bones and joints intravenously on 2 g each 12 h;

• at extremely heavy or zhizneugrozhayushchy infections intravenously on 2 g each 8 h.

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

After an initial load 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	DOSE
> 50 ml/min. (0,52 - 0,83 ml/sec.)	You watch the section "Usual Dose for Adults and Teenagers"
35-50 ml/min. (0,52 – 0,83 ml/sec.)	On 1 g each 12 h
16 – 30 ml/min. (0,27 – 0,50 ml/sec.)	On 1 g each 24 h
6-15 ml/min. (0,10 – 0,25 ml/sec.)	On 500 mg each 24 h
<5 ml/min. (0,08 ml/sec.)	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 are 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 every period of dialysis. At peritoneal dialysis the drug Ceftazidime can be included in dialysis liquid in a dose from 125 mg to 250 mg on 2 l of dialysis liquid.

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/days daily (for one or several introductions). At the patients who are on haemo filtering of low speed appoint the doses recommended at a renal failure.

Usual dose for children. Children aged up to 1st month – intravenous infusion of 30 mg/kg a day (frequency rate 2 introductions). Children from 2 months to 12 years – intravenous infusion of 30-50 mg/kg a day (frequency rate 3 introductions). Each 12th h appoint a dose to 150 mg/kg/days to children with reduced immunity, a mucoviscidosis, meningitis. The maximum daily dose for children should not exceed 6 g.

Preparation of solutions.

1. "Primary" cultivation.

250 mg	1 ml of water for injections at intramuscular introduction	2,5 ml of water for injections at intravenous administration.
500 mg	1,5 ml of water for injections at intramuscular introduction.	5 ml of water for injections at intravenous introduction.
1,0 g	3 ml of water for injections at intramuscular introduction	10 ml of water for injections at intravenous administration

2. "Secondary" cultivation. For intravenous DROP administration the drug Ceftazidime 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:

In the presence of the following diseases or states, it is necessary to weigh carefully ratios of advantage and risk for the patient:

- pregnancy and feeding by a breast;

- newborns and children up to 1 month;

- bleedings in the anamnesis;

- gastrointestinal diseases in the anamnesis , especially, ulcer colitis.

At patients with the allergy to penicillin registered in the anamnesis cross hypersensitivity to cephalosporins at 3-7% of patients is noted. Though at many patients with the allergy to penicillin which is shown in the form of rash, cephalosporins applied without undesirable effects, it is recommended to be careful at purpose of drug Bestum. All cephalosporins 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 heavy, 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 the pseudomembranous colitis caused by Clostridium difficile toxin can develop in time or after use of cephalosporins. In mild cases there is enough drug withdrawal, at heavier - recovery of water-salt and proteinaceous balance is recommended if the listed measures do not help, appoint metronidazole, bacitracin, Vancomycinum.

Influence on ability to driving of motor transport and to control of mechanisms. Considering side reactions of drug, during treatment it is necessary to be careful at control of motor transport or other activity requiring special attention and speed of psychomotor reactions.

Use at pregnancy and feeding by a breast. Use at pregnancy (especially in the first months) is possible only when the potential advantage for mother exceeds risk for a fruit.

Category of action on a fruit on FDA — B. Drug is emitted with breast milk in low concentration therefore in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Side effects:

- from a nervous system and sense bodys: a headache, dizziness, epileptiform attacks, encephalopathy, paresthesia, the "flitting" tremor;

- from bodies of a hemopoiesis: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, lymphocytosis, hemolitic anemia, increase in a prothrombin time, hemorrhage;

- from bodies of a GIT: nausea, vomiting, diarrhea, pain in epigastric area, pseudomembranous colitis, increase in activity of enzymes of blood: (aspartate aminotransferases (nuclear heating plant), alaninaminotranspherase (ALT), alkaline phosphatase (AP), lactate dehydrogenase (LDG), hyperbilirubinemia, cholestasia, orofaringealny candidiasis;

- from urinogenital system: a renal failure (an azotemia, increase in content of urea in blood), an oliguria, an anury, a toxic nephropathy, a mycotic vulvovaginitis;

- 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;

- others: candidiasis, giperkreatininemiya, false positive reaction of urine to glucose, false positive forward reaction of Koombs; reactions in an injection site – morbidity, burning, formation of infiltrates and abscesses (at introduction in oil), phlebitis and thrombophlebitises (at in introduction), nasal bleedings, superinfection.

Interaction with other medicines:

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 the drug in one tube, between their use systems for intravenous administration should be washed out), heparin.

Bacteriostatic antibiotics (including chloramphenicol) reduce effect of drug.

It is impossible to use bicarbonate sodium solution as solvent. Loopback diuretics, aminoglycosides, Vancomycinum, clindamycin reduce clearance of a ceftazidime therefore the risk of nephrotoxic action increases.

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, a 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%, Dextrosum of 10%, a dextran 40 (10%) in solution of sodium of chloride of 0.9%, a dextran 40 (10%) in solution of a dextrose of 5%, a dextran 70 (6%) in solution of sodium of chloride of 0.9%, a dextran 70 (6%) 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 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 to cephalosporins and penicillin.

With care. A renal failure, gastrointestinal diseases (including ulcer colitis in the anamnesis), a concomitant use with loopback diuretics and aminoglycosides, the neonatality period.

Overdose:

Overdose symptoms. Introduction of inadequately high doses of drug Bestum can cause dizziness, paresthesias, a headache, convulsive attacks, deviations in results of laboratory analyses.

Overdose treatment. Specific antidote is absent. Treatment: maintenance of vital signs, at development of spasms – antiepileptic medicines, at patients with damage of kidneys is peritoneal dialysis or a hemodialysis.

Storage conditions:

To store in the place protected from light and moisture at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after expiry date.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous and intramuscular administration. On 250 mg and 500 mg in bottles with a capacity of 10 ml. On 1 bottle together with the application instruction in a cardboard pack. Powder for preparation of solution for intravenous and intramuscular administration. On 1000 mg in bottles with a capacity of 20 ml. On 1 bottle together with the application instruction in a cardboard pack.