Sulzontsef

General characteristics. Structure:

Powder for preparation of solution for in/in and introductions in oil of color, white or white with a yellowish shade.

Active ingredient:  1 фл. цефоперазон (in the form of sodium salt) 1 g; to sulbakta (in the form of sodium salt) 1 g

Pharmacological properties:

Сульзонцеф® - the combined antibacterial drug of a broad spectrum of activity for injections. The main antibacterial component is цефоперазон.

Tsefoperazon - a tsefalosporinovy antibiotic of the III generation for injections. Works bakteritsidno, possesses a broad spectrum of activity; it is highly active concerning gram-positive and gram-negative aerobic and anaerobic microorganisms (including Pseudomonas aeruginosa), is steady against β-lactamelements of gram-positive and gram-negative microorganisms.

Sulbaktam - irreversible inhibitor β-лактамаз which are allocated with the microorganisms steady against a beta laktamnym to antibiotics. Prevents destruction of penicillin and cephalosporins under action β-лактамаз steady microorganisms. Contacting penitsillinsvyazyvayushchy proteins, shows a synergism at simultaneous use with penicillin and cephalosporins. Sulbaktam is active only against Neisseria spp. and Acinetobacter spp.

The combination of a tsefoperazon and sulbaktam is active concerning all microorganisms sensitive to a tsefoperazon, and works sinergidno (reduces to 4 times the minimum overwhelming concentration (MOC) of a combination of antibiotics in comparison with values for each component separately) for the following microorganisms: Haemophilus influenzae, Bacteroides spp., Staphylococcus spp., Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Citrobacter diversus, Enterobacter cloacae.

Сульзонцеф® in vitro is active concerning gram-positive aerobic bacteria: Staphylococcus aureus (including the strains which are forming and not forming a penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (a beta and hemolitic strain of group A), Streptococcus agalactiae (a beta and hemolitic strain of group B), the majority of strains of beta and hemolitic Streptococcus spp., Enterococcus faecalis; gram-negative aerobic bacteria: Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Morganella morganii, Providencia spp. (including Providencia rettgeri), Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica; anaerobic bacteria: Bacteroides spp. (including Bacteroides fragilis), Clostridium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Veillonella spp., Eubacterium spp., Lactobacillus spp.

For studying of sensitivity use of the disks containing 30 mkg of a sulbaktam and 75 mkg of a tsefoperazon (Kirby-Bauer's method) is recommended.

 

Pharmacokinetics. Distribution

Cmax of a sulbaktam and tsefoperazon later in/in administrations of drug in a dose of 2 g (1 g of a sulbaktam and 1 g of a tsefoperazon) within 5 min. averaged 130.2 mkg/ml and 236.8 mkg/ml respectively. It reflects higher Vd of a sulbaktam (from 8 l to 27.6 l) in comparison with that of a tsefoperazon (from 10.2 l to 11.3 l). Serumal concentration is proportional to the entered dose.

As цефоперазон, and to sulbakta, are well distributed in various fabrics and liquids, including bile, a gall bladder, skin, an appendix, fallopian pipes, ovaries, a uterus.

There are no data on existence of any pharmacokinetic interaction between tsefoperazony and sulbaktamy at administration of drug.

At repeated use of significant changes of pharmacokinetics of both components of drug it is noted. At administration of drug each 8-12 h cumulation was not observed.

Removal

About 25% of a dose of a tsefoperazon and 84% of a dose of a sulbaktam are removed by kidneys. The rest of a tsefoperazon is removed generally with bile. T1/2 of a tsefoperazon makes 1.7 h, a sulbaktam - on average about 1 h.

Pharmacokinetics in special clinical cases

Tsefoperazon is actively brought with bile. T1/2 of a tsefoperazon is usually extended, and drug removal by kidneys increases at patients with 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 T1/2 increases by only 2-4 times.

At patients with various function of the kidneys receiving Sulzontsef® 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 T1/2 of a sulbaktam is revealed (on average 6.9 h and 9.7 h in various researches).

The hemodialysis caused considerable changes of T1/2, the general clearance from an organism and Vd of a sulbaktam.

The pharmacokinetics of drug was studied at elderly people with a renal failure and abnormal liver functions. In comparison with healthy volunteers increase in duration of T1/2, decrease in clearance and increase in Vd both tsefoperazon, and sulbaktam is revealed. The pharmacokinetics of a sulbaktam correlated with degree of a renal failure, and pharmacokinetics of a tsefoperazon - with degree of an abnormal liver function.

In researches at children essential changes of pharmacokinetic parameters of components of drug in comparison with those at adults were not revealed. Average T1/2 of a sulbaktam at children made of 0.91 h to 1:42 h, a tsefoperazon - of 1:44 h to 1.88 h.

Indications to use:

Treatment of the bacterial infections caused by microorganisms, sensitive to drug:

— infections of upper and lower parts of respiratory tracts (pharyngitis, tonsillitis, sinusitis, bronchitis, pneumonia, bronchial pneumonia, empyema, abscess of lungs);

— infections of urinogenital ways (pyelonephritis, cystitis, prostatitis, endometritis, gonorrhea, vulvovaginitis);

— intraabdominal infections (peritonitis, cholecystitis, cholangitis);

— infections of ENT organs (acute average otitis, sinusitis, quinsy);

— infections of skin and soft tissues (furunculosis, abscess, pyoderma, lymphadenitis, lymphangitis);

— osteomyelitis, infections of joints;

— sepsis;

— meningitis.

Prevention of infectious complications after abdominal, gynecologic and orthopedic operations, in cardiovascular surgery.

Route of administration and doses:

Drug appoint in/in (struyno or kapelno) or in oil.

Total doses of a tsefoperazon and sulbaktam are provided below (in the ratio 1:1).

The adult appoint on 2-4 g/days at an interval of 12 h; at the heavy, persistently proceeding infections - to 8 g/days the Maximum daily dose - 8 g (4 g of a tsefoperazon + 4 g of a sulbaktam).

Carry out by the patient with a chronic renal failure (KK less than 30 ml/min.) dose adjustment. At KK of 15-30 ml/min. the maximum dose of a sulbaktam makes on 1 g 2 (2 g/days), at KK less than 14 ml/min. - on 500 mg 2 (1 g/days).

At an abnormal liver function and obstruction of bilious ways the maximum daily dose of a tsefoperazon - no more than 2 g.

To children drug is appointed at the rate of 40-80 mg/kg/days in 2-4 introductions, the newborn within the first week of life - in 2 introductions; at heavy, it is long the proceeding infections - to 160 mg/kg / (80 mg/kg/days of a tsefoperazon + 80 mg/kg/days of a sulbaktam). The maximum daily dose of Sulzontsef - 160 mg/kg / In need of introduction more than 80 mg/kg/days calculated on activity of a tsefoperazon, increase in a dose is reached due to additional introduction only of one tsefoperazon.

Rules of preparation and administration of drug

For in/in bolyusny introductions contents of a bottle dissolve in the adequate volume of 5% of solution of a dextrose (glucose), 0.9% of solution of sodium of chloride, 5% of solution of a dextrose (glucose) in 0.225% solution of sodium of chloride, 5% of solution of a dextrose (glucose) in 0.9% solution of sodium of chloride or sterile water for injections, and enter within 3 min.

For in/in infusional introductions dissolve as it was stated above. Then part up to 20-100 ml and enter within 15-60 min.

For introduction in oil for dissolution use sterile water for injections. Preparation of solution with use of lidocaine is carried out in 2 steps: at first sterile water for injections, then - 2% lidocaine solution before receiving 0.5% of solution of lidocaine. The total volume of solvent makes 6.7 ml.

Features of use:

Considering a wide range of activity, it is possible to use drug as monotherapy.

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

At patients with diseases of a liver and/or with obstruction of biliary tract of T1/2 of a tsefoperazon increases, removal by kidneys is increased. At a heavy abnormal liver function concentration of a tsefoperazon in bile is therapeutic, T1/2 increases by 2-4 times. Change of a dose and control of concentration of a tsefoperazon in blood serum is required at the expressed obstruction of bilious ways, a heavy liver failure (in these cases the maximum daily dose of drug - 2 g).

The patients adhering to a defective diet or having disturbance of absorption of food are subject to risk of development of deficit of vitamin K (patients with a mucoviscidosis; the patients who are for an appreciable length of time on parenteral food). At such patients control of a prothrombin time has to be exercised; in case of need appoint vitamin K. The mechanism of development of deficit of vitamin K is suppression of intestinal microflora which normal synthesizes this vitamin.

At prolonged treatment it is necessary to control indicators of function of kidneys, a liver and the hemopoietic system.

During therapy false positive results of definition of glucose in urine when using solutions of Benedict or Felinga can be observed, false positive reaction of Koombs.

Treatment of premature newborns is carried out if the possible advantage exceeds potential risk.

Side effects:

From the alimentary system: diarrhea, nausea, vomiting, pseudomembranous colitis, increase in activity of hepatic transaminases and ShchF, hyperbilirubinemia.

From bodies of a hemopoiesis: anemia, neutropenia, thrombocytopenia, bleedings (deficit of vitamin K).

Laboratory indicators: giperkreatininemiya, prothrombinopenia.

Allergic reactions: urticaria, makulopapulezny rash, fever, eosinophilia; seldom - an acute anaphylaxis.

Local reactions: at in introduction - phlebitis; at introduction in oil - morbidity in an injection site.

Interaction with other medicines:

Synergism of antibacterial action is observed at simultaneous use of a tsefoperazona/sulbaktam with aminoglikozidny antibiotics.

The ethanol use (at the same time or during the next 5 days after the end of treatment) strengthens risk of development of disulfiramopodobny reaction (inflows, the increased sweating, a headache, tachycardia).

Pharmaceutical interaction

Drug is compatible to water for injections, 5% solution of a dextrose (glucose), 0.9% solution of sodium of chloride, 5% solution of a dextrose (glucose) in 0.225% solution of sodium of chloride, 5% solution of a dextrose (glucose) in 0.9% chloride sodium solution.

Drug is incompatible with Ringer's solution, 2% hydrochloride lidocaine solution (initial use of water for injections leads to formation of compatible mix), aminoglycosides (if the combination therapy is necessary, lead her by way consecutive fractional to infusions of two medicines, using 2 separate systems for in/in transfusions; in an interval between introduction of doses the system has to be washed out by compatible solvent).

Contraindications:

— lactation period;

— hypersensitivity to drug components, including to others beta лактамным to antibiotics.

With care it is necessary to appoint drug at a renal and/or liver failure, colitis (including in the anamnesis), the premature newborn, pregnancy.

 

Use of the drug SULZONTSEF® at pregnancy and feeding by a breast
Use of drug at pregnancy and in the period of a lactation is carried out if the possible advantage exceeds potential risk.

 

Use at abnormal liver functions
With care it is necessary to appoint drug at a liver failure.

 

Use at renal failures
With care it is necessary to appoint drug at a renal failure.

Carry out by the patient with a chronic renal failure (KK less than 30 ml/min.) dose adjustment. At KK of 15-30 ml/min. the maximum dose of a sulbaktam makes 1 g 2, at KK less than 14 ml/min. - 500 mg 2.

Overdose:

Symptoms: neurologic disturbances, including spasms.

Treatment: carry out symptomatic therapy (including sedative therapy). The hemodialysis is effective.

Storage conditions:

Drug should be stored in dry, protected from light, the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Bottles of 20 ml (1) - packs cardboard.
Bottles of 20 ml (5) - packs cardboard.
Bottles of 20 ml (10) - packs cardboard.
Bottles of 20 ml (50) - boxes cardboard.
Bottles of 20 ml (5) - planimetric strip packagings (1) - packs cardboard.
Bottles of 20 ml (5) - planimetric strip packagings (2) - packs cardboard.
Bottles of 20 ml (1) complete with solvent (water for and - amp. 5 ml 1) - planimetric strip packagings (1) - packs cardboard.
Bottles of 20 ml (1) complete with solvent (water for and - amp. 5 ml 2) - planimetric strip packagings (1) - packs cardboard.
Bottles of 20 ml (5) - planimetric strip packagings (1) complete with solvent (water for and - amp. 5 ml (5) - planimetric strip packagings (1)) - packs cardboard.
Bottles of 20 ml (5) - planimetric strip packagings (1) complete with solvent (water for and - amp. 5 ml (5) - planimetric strip packagings (2)) - packs cardboard.