Цебанекс

General characteristics. Structure:

Active ingredients: 1 g of a sulbaktam, 1 g of a tsefaperazon.

Pharmacological properties:

Pharmacodynamics. An antibacterial component of a tsefoperazon + the sulbaktama is цефоперазон - a tsefalosporinovy antibiotic of the third generation which affects sensitive microorganisms during their active reproduction by oppression of biosynthesis of a mukopeptid of a cell wall. Sulbaktam has no clinically significant antibacterial activity (an exception Neisseriaceae and Acinetobacter make), but is irreversible inhibitor of the majority of the main beta лактамаз which are produced steady against a beta laktamnym to antibiotics by microorganisms. Sulbaktam contacts some penitsillinsvyazyvayushchy proteins therefore the combination of a tsefoperazon and a sulbaktam often has more expressed effect on sensitive strains, than simply цефоперазон.

The combination of a tsefoperazon with sulbaktamy is active concerning all microorganisms sensitive to a tsefoperazon. Besides, it possesses a synergism concerning various microorganisms, first of all: Haemophilus influenzae, Bacteroides species, Staphylococcus species, Acinelobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.

Tsefoperazon + to sulbakta is active in vitro concerning a wide range of the following clinically significant microorganisms:

Gram-positive microorganisms. Staphylococcus aureus (which is producing and not producing a penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (a beta and hemolitic streptococcus of group A), Streptococcus agalactiae (a beta and hemolitic streptococcus of group B), the majority of other strains of beta and hemolitic streptococci, Streptococcus faecalis (enterococci).

Gram-negative microorganisms. Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, Haemophilis influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia species, Serratia species (including Serratia marcescens). Salmonella species and Shigella species, Pseudomonas aeruginosa and some other Pseudomonas species, Acinelobacler calcoacelicus. Neisseria gonorrhoeae, Neisseria meningitidis, Bordelella pertussis, Yersinia enlerocolitica.

Anaerobic microorganisms. Gram-negative sticks (including Bacleroides fragilis, other Bacteroides species and Fusobacterium species).

Gram-positive and gram-negative cocci (including Peptococcus species, Peplostreplococcus species and Veillonella species).

Gram-positive sticks (including Clostridium species, Eubacterium species and Lactobacillus species).

Pharmacokinetics. As to sulbakta, and цефоперазон also others are well distributed in various fabrics and liquids, including bile, a gall bladder, skin, an appendix, pipe fallopiyeva, ovaries, a uterus.

The maximum concentration of a sulbaktam and tsefoperazon after intravenous administration of 2 g of a tsefoperazon of a sulbaktam (1 g of a sulbaktam, 1 g of a tsefoperazon) within 5 min. average 130.2 mkg/ml and 236.8 mkg/ml respectively. It reflects higher volume of distribution of a sulbaktam (Vd of 18,0-27,6 l) in comparison with that of a tsefoperazon (Vd = 10.2-11.3 l).

About 84% of a sulbaktam and 25% of a tsefoperazon are removed by kidneys. The rest of a tsefoperazon is removed generally with bile. At parenteral administration of drug the elimination half-life of a sulbaktam averages about 1 h, a tsefoperazon - 1.7 h. Serumal concentration is proportional to the entered dose.

At repeated use of significant changes of pharmacokinetics of both components of a tsefoperazon + the sulbaktama is not noted.

At administration of drug each 8-12 h cumulation it is not observed.

Pharmacokinetics at an abnormal liver function. Tsefoperazon is actively brought with bile. The elimination half-life of a tsefoperazon is usually extended, and drug excretion kidneys increases at the patients having diseases of a liver and/or obstruction of bilious ways. Even at a heavy abnormal liver function in bile therapeutic concentration of a tsefoperazon is reached, and the elimination half-life increases by only 2-4 times.

Pharmacokinetics at a renal failure. Patients with various degree have renal failures, receiving цефоперазон + to sulbakta, high correlation between the general clearance of a sulbaktam from an organism and settlement clearance of creatinine is revealed. At patients with a terminal renal failure considerable lengthening of an elimination half-life of a sulbaktam is revealed (on average 6.9 h and 9.7 h in various researches). The hemodialysis causes considerable changes of an elimination half-life, the general clearance from an organism and the volume of distribution of a sulbaktam.

Pharmacokinetics at elderly people. At elderly people with a renal failure and the broken function of a liver increase in duration of an elimination half-life, decrease in clearance and increase in volume of distribution both a sulbaktam, and tsefoperazon is observed. The pharmacokinetics of a sulbaktam correlates with degree of a renal failure, and pharmacokinetics of a tsefoperazon - with degree of an abnormal liver function.

Pharmacokinetics at children. Children have no essential differences of pharmacokinetics of components of a tsefoperazon + a sulbaktam in comparison with adults. The elimination half-life of a sulbaktam at children varies from 0.91 to 1.42 h, and a tsefoperazona - from 1.44 to 1.88 h.

Indications to use:

Tsefoperazon + is shown to sulbakta for treatment of the following infections caused by sensitive microorganisms:

— infections of upper and lower parts of respiratory tracts;

— infections of urinary tract;

— peritonitis, cholecystitis, cholangitis and other intraabdominal infections;

— sepsis;

— meningitis;

— infections of skin and soft tissues;

— infections of bones and joints;

— inflammatory diseases of bodies of a small pelvis, endometritis, gonorrhea and other infections of an urinogenital path.

Route of administration and doses:

Intravenously and intramusculary.

Use for adults. At adults цефоперазон + sulbakta are recommended to use in the following daily doses:

Ratio	Tsefoperazon + Sulbaktam ()	Sulbaktam dose ()	Tsefoperazon dose ()
1:1	2.0-4.0	1.0-2.0	1.0-2.0

The daily dose should be divided into equal parts and to enter each 12 h.

At heavy or refractory infections the daily dose of a tsefoperazon + a sulbaktama can be increased to 8 g (at a ratio of the main components 1:1, i.e. 4 g of a tsefoperazon and 4 g of a sulbaktam). In need of introduction more than 8 g (at a ratio of the main components 1:1) increase in a dose is reached due to additional introduction of a tsefoperazon. The dose should be divided into equal parts and to enter each 12 h.

The recommended maximum daily dose of a sulbaktam makes 4 g.

Use at a renal failure. Patients with clearance of creatinine of 15-30 ml/min. have to receive at most 1 g of a sulbaktam each 12 h (the maximum daily dose of a sulbaktam - 2 g), patients with clearance of creatinine less than 15 ml/min. - at most 500 mg of a sulbaktam each 12 h (the maximum daily dose of a sulbaktam - 1 g). At heavy infections additional introduction of a tsefoperazon can be required.

The pharmacokinetics of a sulbaktam considerably changes at a hemodialysis. The elimination half-life of a tsefoperazon from blood serum decreases a little during a hemodialysis. In this regard administration of drug should be carried out after dialysis. At patients with an abnormal liver function and the accompanying renal failure if regular monitoring of serumal concentration of a tsefoperazon is not carried out, the maximum daily dose should not exceed 2 g (see the section "Special Instructions").

Use for children. At children цефоперазон + sulbakta are recommended to apply in the following daily doses:

Ratio	Tsefoperazon + Sulbaktam (mg/kg/days)	Sulbaktam dose (mg/kg/days)	Tsefoperazon dose (mg/kg/days)
1:1	40-80	20-40	20-40

The dose should be divided into equal parts and to enter each 6-12 h.

At heavy or refractory infections the daily dose of a tsefoperazon + a sulbaktama can be increased to 160 mg/kg/days (at a ratio of the main components 1:1, i.e. 80 mg/kg/days of a tsefoperazon and 80 mg/kg/days of a sulbaktam). In need of introduction more than 160 mg/kg/days (at a ratio of the main components 1:1) increase in a dose is reached due to additional introduction of a tsefoperazon. The dose should be divided into equal parts and to enter each 6-12 h.

Use for newborns. At newborns within the first week of life the drug should be administered each 12 h. The maximum daily dose of a sulbaktam at children should not exceed 80 mg/kg/days.

Way of preparation of solutions for parenteral use. Solution preparation:

General dose ()	Equivalent doses ефоперазон + to sulbakta ()	Solvent volume	Max, final конц. (mg/ml)
1,0	0,5 + 0,5	3,4	125 +125

Intramuscular introduction. For preparation of solution for intramuscular introduction it is possible to use water for injections (see the table above).

For convenience of introduction it is also possible to prepare drug solution with concentration of a tsefoperazon of 250 mg/ml or more. In this case solution is prepared in two stages, using as solvents at first water for injections, and then 2% hydrochloride lidocaine solution (see below) as hydrochloride lidocaine solution directly cannot be applied to initial dissolution.

Preparation of solution with lidocaine use. Originally powder is dissolved in 1,3 ml of sterile water for injections, and then add 0,4 ml of 2% of solution of lidocaine of a hydrochloride. The total volume of solvent makes 1,7 ml. Final solution will contain in 1 ml 0,5% of solution of lidocaine of a hydrochloride about 250 mg of a tsefoperazon and about 250 mg of a sulbaktam.

Intravenous administration. For preparation of solution for infusions of 1 g (0,5 g + 0,5 g) the tsefoperazon + a sulbaktam is dissolved in the initial volume (about 3,4 ml) of one of the following infusion solutions: 5% solution of glucose (dextrose), 5% glucose solution in normal saline solution, 5% glucose solution in 0,225% solution of sodium chloride, 0,9% solution of sodium chloride or sterile water for injections, and then dilute to 20 ml with the same solution.

Preparations of solution with use of a shatan of Ringer. As Ringer's lactate is not suitable for initial cultivation, solution is prepared in two stages: at first use sterile water for injections (see the table above), and then dissolve the received solution with solution of a lactate of Ringer to concentration of a sulbaktam of 5 mg/ml (2 ml of initial solution part in 50 ml of solution of a lactate of Ringer or 4 ml in 100 ml of solution of a lactate of Ringer).

Infusion is carried out within 15-60 min. For an intravenous injection contents of each bottle should be dissolved in 3.4 ml of one of the solvents described in preparation of solution for infusions (see above) and to enter within at least 3 minutes.

Features of use:

Use at pregnancy and feeding by a breast. At pregnancy drug is used only if the expected advantage for mother exceeds potential risk for a fruit.

In case of administration of drug in the period of a lactation breastfeeding is recommended to be stopped.

Use at abnormal liver functions. With care at heavy abnormal liver functions.

Use at renal failures. With care at heavy renal failures.

Use for children. The maximum daily dose of a sulbaktam at children should not exceed 80 mg/kg/days.

Special instructions. At the patients receiving beta лактамные antibiotics, including cephalosporins cases of reactions of hypersensitivity which risk of development is higher at patients at whom in the anamnesis hypersensitivity reactions were observed are described. At emergence of allergic reaction it is necessary to cancel drug and to appoint the corresponding therapy.

At anaphylactic reactions urgent introduction of Epinephrinum is necessary. According to indications appoint oxygen, intravenously enter glucocorticosteroids and provide passability of respiratory tracts, including an intubation.

Change of a dose can be required in cases of heavy obstruction of bilious ways, a heavy abnormal liver function, and also a renal failure, combined with any of the specified states.

At patients with an abnormal liver function and the accompanying renal failure monitoring of serumal concentration of a tsefoperazon and correction of its dose in case of need is necessary.

At treatment tsefoperazony, as well as other antibiotics, deficit of vitamin K in rare instances developed. It probably suppression of normal intestinal microflora which synthesizes this vitamin is the reason. It is possible to carry the patients receiving defective food, suffering from malabsorption to risk group (for example, at a mucoviscidosis) and it is long being on intravenous artificial nutrition. In such cases, and also at the patients receiving anticoagulants it is necessary to control a prothrombin time and in the presence of indications to appoint vitamin K.

At prolonged treatment tsefoperazony + sulbaktamy, as well as other antibiotics, the excess growth of insensitive microorganisms can be observed. At long therapy it is recommended to control periodically indicators of function of internals, including kidneys, a liver and system of a hemopoiesis. It is especially important for newborns, first of all premature, and small children.

At simultaneous use with aminoglycosides it is necessary to control function of kidneys.

Side effects:

Drug is usually well transferred. The following reactions were noted:

Cardiovascular system: lowering of arterial pressure.

Digestive tract: diarrhea, nausea, vomiting, pseudomembranous colitis.

Allergic reactions: makulopapulezny rash, small tortoiseshell, and also itch, Stephens-Johnson's syndrome, acute anaphylaxis. The risk of reactions is higher at patients with allergic reactions in the anamnesis.

System of a hemopoiesis: decrease in number of neutrophils; at prolonged treatment - a reversible neutropenia, decrease in level of hemoglobin and a hematocrit, a passing eosinophilia, thrombocytopenia, a leukopenia, a prothrombinopenia, bleedings (owing to deficit of vitamin K).

Local reactions: drug is well transferred at intramuscular introduction. Sometimes after an intramuscular injection passing pain and burning in the place of an injection is observed. At intravenous administration through a catheter phlebitis in an injection site can develop.

Laboratory indicators: passing increase in "hepatic" transaminases - aspartate aminotransferases, alaninaminotranspherases, an alkaline phosphatase and bilirubin in blood serum, a hamaturia, a giperkreatininemiya. At some patients during treatment false positive test of Koombs was observed. When using solution of Benedict or Felinga false positive reaction to glucose in urine can be observed.

Others: headache, fever, fever, vasculitis.

Interaction with other medicines:

Aminoglycosides. + a sulbaktam and aminoglycosides it is not necessary to mix solutions of a tsefoperazon, considering pharmaceutical incompatibility between them. If the combination therapy by drug of a tsefoperazon + a sulbaktam and aminoglycoside is carried out, then two drugs enter by consecutive infusions with use of separate secondary catheters, and wash out primary catheter between introduction of doses of drugs. Intervals between introduction of a tsefoperazon + a sulbaktam and aminoglycoside during the day have to be as much as possible.

Alcohol. At alcohol intake during treatment tsefoperazony and within 5 days after its introduction the reactions which are characterized by inflows, perspiration, a headache and tachycardia therefore patients should be warned about a possibility of their emergence at the use of alcoholic beverages against the background of treatment tsefoperazony + sulbaktamy were registered. At patients who need artificial nutrition (inside or parenterally) it is necessary to avoid use of the solutions containing ethanol.

Ringer's solution, 2% hydrochloride lidocaine solution. Solution of a tsefoperazon + a sulbaktama is incompatible with Ringer's solution and 2% hydrochloride lidocaine solution at direct mixing. Compatibility is reached as a result of two-stage preparation: originally цефоперазон + to sulbakta dissolve in water for injections, and then add Ringer's solution or 2% hydrochloride lidocaine solution.

Contraindications:

Allergy to penicillin, to sulbakta, цефоперазон or any other beta лактамные antibiotics.

With care: at heavy abnormal liver functions and kidneys; at colitis (including in the anamnesis); at premature newborns.

Overdose:

Symptoms: neurologic disturbances, including spasms.

Treatment: symptomatic.

In case of overdose at patients with a renal failure removal of drug from an organism can be promoted by a hemodialysis.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. List B. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Bottles (1) - packs cardboard.
Bottles (50) - packs cardboard.