Klaforan

General characteristics. Structure:

 Rolled into one 1 g of sterile powder of a tsefotaksim contains that corresponds to 1, 048 g of a tsefotaksim of sodium salt.

Pharmacological properties:

Pharmacodynamics. A semi-synthetic antibiotic of group of cephalosporins III of generation for parenteral use. Tsefotaksim acts bakteritsidno. It is also steady against action of the majority of B-laktamaz.

Are usually sensitive to drug: Aeromonas hydrophila; Bacillus subtilis; Bordetella pertussis; Borrelia burgdorferi; Moraxella (Branhamella) catarrhalis; Citrobacter diversus; Clostridium perfringens; Corynebacterium diphtheriae; Escherichia coli; Enterobacter spp. (sensitivity depends on data of epidemiology and on stability level in each specific country); Erysipelothrix insidiosa; Eubacterium; Haemophilus penitsillinazoobrazuyushchy and nepenitsillinazoobrazuyushchy strains, including ampi-R; Klebsiella pneumoniae; Klebsiella oxytoca; Methi-S-Staphylococcus, including penitsillinazoobrazuyushchy and nepenitsillinazoobrazuyushchy strains; Morganella morganii; Neisseria gonorrhoeae, including penitsillinazoobrazuyushchy and nepenitsillinazoobrazuyushchy strains; Neisseria meningitidis; Propionibacterium; Proteus mirabilis, vulgaris; Providencia; Streptococcus pneumoniae, Salmonella; Seratia spp. (sensitivity depends on data of epidemiology and on stability level in each specific country); Shigella, Streptococcus spp.; Veillonella; Yersinia (sensitivity depends on data of epidemiology and on stability level in each specific country).

Are steady against drug: Acinetobacter baumannii, Bacteroides fragilis; Clostridium difficile; Enterococcus; gram-negative anaerobe bacterias; Listeria monocytogenes, Methi-R staphylococcus; Pseudomonas aeruginosa, Pseudomonas cepacia; Stenotrophomonas maltophilia.

Pharmacokinetics. At adults — in 5 minutes after 1 g of a tsefotaksim, single in/in introductions, concentration in a blood plasma makes 100 mkg/ml. After introduction in oil of a tsefotaksim in the same dose the maximum concentration in a blood plasma is found in 0,5 hours and makes from 20 to 30 mkg/ml.

T1/2 of drug makes 1 h at in introduction and 1–1,5 h at introduction in oil.
Linkng with proteins of plasma (preferential albumine) averages 25–40%.
About 90% of the entered dose are removed with urine: 50% — in not changed look and about 20% — in the form of a metabolite of a dezatsetiltsefotaksim.

At elderly (80 years are more senior) T1/2 of a tsefotaksim increases to 2,5 h.

At adults with an impaired renal function — the volume of distribution does not change, and T1/2 does not exceed 2,5 h, even at the last stages of a renal failure.

Children, newborns and prematurely been born babies have a level of a tsefotaksim in plasma and the volume of distribution are similar to that at the adults receiving the same dose of drug in mg/kg. T1/2 of a tsefotaksim makes from 0,75 to 1,5 h.
Newborns and prematurely been born children have a level of a tsefotaksim in plasma and the volume of distribution are similar to that at children. Average T1/2 of a tsefotaksim makes from 1,4 to 6,4 h.

Indications to use:

Tsefotaksim is intended for treatment of the infections caused by microorganisms, sensitive to drug: respiratory infections;
- infections of urinogenital ways;
- septicaemia, bacteremia;
- endocarditises;
- intraabdominal infections (including peritonitis);
- meningitis (except for listeriozny) and other infections of TsNS;
- infections of skin and soft tissues;
- infections of bones and joints;
- prevention of infections after surgeries on a GIT, urological and obstetric and gynecologic operations.

Route of administration and doses:

Tsefotaksim is entered intramusculary or intravenously (in the form of a slow injection or infusion).

Dosage at adults with normal function of kidneys: At uncomplicated gonorrhea the single dose makes 0,5–1 g and is entered intramusculary once.
At uncomplicated infections of moderate severity tsefotaksy enter in a single dose 1–2 g intramusculary or intravenously, in 8–12 h, thus, the daily dose fluctuates from 2 to 6 g.
At heavy infections the single dose makes 2 g and is entered intravenously in 6–8 h, thus, the daily dose fluctuates from 6 to 8 g.
In cases when the infection is caused by insufficiently sensitive strains, the test of definition of sensitivity to an antibiotic — the only means of confirmation of efficiency of a tsefotaksim.

Dosage at adults with an impaired renal function:
In cases when creatinine level less than 10 ml/min., a half of a single dose is used. The interval of introduction remains invariable (see above).
 Respectively the daily dose will be also reduced twice.
In cases when Cl of creatinine cannot be measured, it can be calculated on serum creatinine level, using Kokroft's formula for adults.
 
For men:
Cl of creatinine (ml/min.) = Weight (kg) × (140 − age)/72 × creatinine (mg/%)
or:
Weight (kg) × (140 − age)/0,814 × creatinine (mmol/l)
For women:
Cl of creatinine (ml/min.) = 0,85 × an indicator at men

For the patients who are on a hemodialysis: 1–2 g a day, depending on weight of an infection. In day of dialysis by tsefotaksy it is entered after the end of dialysis.

At prematurely been born children (to 1 week of life) the daily dose of drug makes 50–100 mg/kg and is entered in/in with an interval of 12 h.
At prematurely been born children (1–4 weeks of life) the daily dose of drug makes 75–150 mg/kg and is entered in/in with an interval of 8 h.
At children with body weight to 50 kg the daily dose of drug makes 50–100 mg/kg and is entered intravenously or intramusculary with an interval of 6-8 h.

Note: the daily dose never has to exceed 2 g. In case of heavy infections, for example at meningitis, increase in a daily dose is possible twice. Intramuscular introduction with 1% lidocaine strictly contraindicated children up to 2,5 years.

To children with the body weight of 50 kg and more drug is appointed in the same dose, as the adult.

For the purpose of prevention of development of infections before surgery usually enter 1 g intramusculary or intravenously from the beginning of anesthesia, with repeated introduction in 6–12 h after operation.
When performing Cesarean section at the time of imposing of clips on an umbilical vein intravenously enter 1 g of drug, then in 6–12 h repeatedly enter 1 g of a tsefotaksim intramusculary or intravenously.

Way and duration of use: for intramuscular to dissolve injections tsefotaksy sterile water for injections in number of 4 ml for 1 g and 10 ml — for 2 g. For vnturivenny infusion of 1 or 2 g of drug dissolve in 40–100 ml of sterile water for injections or infusion solution. The injection of solution has to be carried out slowly within 3–5 min., in view of possible development threatened to life of arrhythmias at introduction of a tsefotaksim through the central venous catheter.

At intramuscular introduction bottle contents with tsefotaksimy can be dissolved in water for injections or in 1% lidocaine solution. In case of lidocaine use strictly contraindicated intravenous administration of drug (see. "Special instructions").

Duration of a course of treatment is established individually.

Note: it is necessary to provide aseptic conditions at cultivation of contents of a bottle and preparation of solution (especially if divorced tsefotaksy it is entered not at once).

Features of use:

Anaphylactic reactions:
purpose of cephalosporins demands collecting the allergological anamnesis (allergic diathesis, reactions of hypersensitivity to β-laktamny antibiotics);
if at the patient hypersensitivity reaction developed, then treatment has to be stopped;
use of a tsefotaksim is strictly contraindicated at patients with the instruction in the anamnesis on reaction of immediate hypersensitivity to cephalosporins. In case of any doubts presence of the doctor at the first administration of drug is obligatory in view of possible anaphylactic reaction;
the cross allergy between cephalosporins and penicillin which arises in 5–10% of cases is known. At persons in whose anamnesis there are instructions on an allergy to penicillin drug is used with extreme care.

Pseudomembranous colitis

In the first weeks of treatment there can be pseudomembranous colitis which is shown heavy, long diarrhea. The diagnosis is confirmed at a kolonoskopiya and/or a histologic research. This complication is regarded as very serious: immediately stop Klaforan's introduction and appoint the adequate therapy including peroral Vancomycinum or metronidazole.
When using as solvent of lidocaine it is necessary to consider information provided in the section "Contraindications".

Side effects:

Anaphylactic reactions: a Quincke's disease, a bronchospasm, weakness, it is rare — an acute anaphylaxis.
Skin reactions: rash, reddening, urtikariya. As well as in a case with other cephalosporins, development of such complications as a multiformny erythema, Stephens-Johnson's syndrome, a toxic necrolysis of skin is very seldom possible.
Gastrointestinal reactions: there can be nausea, vomiting, abdominal pains, diarrhea. As well as at purpose of other antibiotics of a broad spectrum of activity, diarrhea can be a coloenteritis symptom that in some cases is followed by emergence of blood in Calais. A special form of a coloenteritis is pseudomembranous colitis (see. "Special instructions").
Reactions from a liver: increase in liver enzymes (ALT, nuclear heating plant, LDG, GGT, ShchF) and/or bilirubin.
Reactions from peripheral blood: a neutropenia, it is rare — an agranulocytosis, an eosinophilia, thrombocytopenia, in isolated cases — hemolitic anemia.
Reactions from kidneys: deterioration in function of kidneys (increase in level of creatinine), especially at the combined use with aminoglycosides, cases of intersticial nephrite are very seldom noted.
Reactions from TsNS: encephalopathy (in case of introduction of high doses), especially at patients with a renal failure.
Reactions from cardiovascular system: in isolated cases — arrhythmias, after bolyusny introduction through the central venous catheter (see. "Route of administration and doses").
Others: fever, an inflammation in the place of an injection, superinfection.
At treatment of borreliosis: Yarisha-Gerksgeymer's reaction (during the first days of treatment), skin rash, an itch, fever, a leukopenia, increase in level of enzymes of a liver, the complicated breath and discomfort in joints.

Except the above-mentioned, it is necessary to control drug rate of administering (See. "Route of administration and doses"), and also to control function of kidneys in all cases of the combined use of a tsefotaksim with aminoglycosides.

At the patients demanding sodium consumption restriction it is necessary to take into account the content of sodium in a tsefotaksim of sodium salt (48,2 mg/g). With duration of a course of treatment (more than 10 days) it is necessary to control quantity of leukocytes and, in case of a neutropenia, treatment should be stopped.

Interaction with other medicines:

Probenetsid detains excretion and increases plasma concentration of cephalosporins.

As well as in case of other cephalosporins, tsefotaksy can exponentiate nephrotoxic effect of the drugs possessing nephrotoxic action.

During therapy by cephalosporins emergence of positive test of Koombs is possible.

Use of glyukozooksidazny methods of determination of level of sugar in blood, in view of development of false positive results when using nonspecific reactants is recommended.

Instructions on compatibility: tsefotaksy should not mix up with other antibiotics, both in one syringe, and in one infusion solution.
It also concerns aminoglycosides.
For infusions the following solutions can be used (concentration of a tsefotaksim of 1 g / 250 ml): water for injections, 0,9% solution of sodium chloride, 5% of Dextrosum, Ringer's solution, sodium lactate, and also: Gemaktsel, Yonosteril, Macrodexum of 6%, Reomakrodeks of 12%, Tutofuzin V.

Contraindications:

Hypersensitivity to cephalosporins;

for the forms containing lidocaine:
hypersensitivity to lidocaine or other local anesthetic of amide type;
 
endocardiac blockade without the established pacemaker;
 
heavy heart failure;
 
intravenous administration;
 
children aged up to 2,5 years (intramuscular introduction).

Use at pregnancy and feeding by a breast

Tsefotaksim gets through a placental barrier.
The researches conducted on animals did not reveal teratogenic effect of drug. However safety of use of a tsefotaksim at pregnancy at the person was not defined therefore drug should not be used during pregnancy.
Tsefotaksim gets into breast milk therefore in need of purpose of drug breastfeeding should be interrupted.

Overdose:

There is a risk of development of reversible encephalopathy when using high doses of β-laktamny antibiotics, including tsefotaksy. There is no specific antidote.

Storage conditions:

To store at a temperature below +25 °C in protected from light and the place, unavailable to children.

Period of validity

2 years. After a period of validity drug cannot be used.

After cultivation

For injections in oil: sterile powder of a tsefotaksim after cultivation in water or 0,5 or 1% solution of lidocaine of a hydrochloride is chemically stable during 8 h (at the room temperature not above +25 °C) or during 24 h (at a temperature of 2-8 °C, the place protected from light).

For injections or infusions at dissolution by water for injections: during 12 h (at the room temperature not above +25 °C) or during 24 h (at a temperature of 2-8 °C, in the place protected from light). The pale yellow shade of solution does not mean decrease of the activity of an antibiotic.

For infusions in infusion solutions: sterile powder of a tsefotaksim is chemically stable during 8 h after cultivation in solution Gemaktsel, Yonosteril or Tutofuzin, and during 6 h after cultivation in 10% glucose solution, Macrodexum or Reomakrodeks.

Issue conditions:

According to the recipe

Packaging:

On 1 g of drug in the glass colourless bottle corked by a rubber bung and which is pressed out by an aluminum cap, supplied with a plastic lid. On 1 bottle together with the application instruction in a cardboard pack.