Сульперацеф®

General characteristics. Structure:

Active ingredient: 0,25 g, 0,5 g or 1,0 g of a tsefoperazon of sodium (in recalculation in цефоперазон); 0,25 g, 0,5 g or 1,0 g of a sulbaktam of sodium (in recalculation in sulfbakta).
 
Antibiotic 3 generations of cephalosporins + inhibitor beta лактамаз.

Pharmacological properties:

Pharmacodynamics. The antibacterial Sulperatsefa® component is цефоперазон - cephalosporin of the third generation which bactericidal effect is connected with an inactivation of enzymes of the transpeptidases participating in synthesis of a peptidoglikan - the main structural component of a cell wall of bacteria. Disturbance of synthesis of a peptidoglikan leads to death of microorganisms.

Sulbaktam of sodium - derivative the main kernel of penicillin. Sulbaktam has no clinically significant antibacterial activity (an exception Neisseriaceae, Acinetobacter spp make.), however is irreversible inhibitor of the majority of the main bacterial beta лактамаз (including plasmid beta lactamelements), the microorganisms destroying penicillin and cephalosporins and defining resistance to a beta laktamnym to antibiotics, and also contacts some penitsillinsvyazyvayushchy proteins.

Therefore, the combination of a sulbaktam with tsefoperazony has more expressed bactericidal effect on strains, sensitive to a tsefoperazon, and works sinergidno for various microorganisms, first of all, of producers beta лактамаз: Staphylococcus spp., Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus, Bacteroides spp.

Сульперацеф® in vitro in the relation is active: gram-positive aerobes - Staphylococcus aureus (which are producing and not producing a penicillinase of strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, many strains of Enterococcus faecalis.

Gram-negative aerobes - Acinetobacter calcoaceticus, Bordetella pertussis, Escherichia coli, Klebsiella spp., including Klebsiella pneumoniae, Enterobacter spp., including Enterobacter aerogenes and Enterobacter cloacace, Citrobacter spp., including Citrobacter freundii and Citrobacter diversus, Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia spp., Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa and some other Pseudomonas spp., Neisseria gonorrhoeae, Neisseria meningitidis, Yersinia enterocolitica

Anaerobic microorganisms - Bacteroides fragilis, other Bacteroides spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Lactobacillus spp., Peptococcus, Peptostreptococcus and Veillonella spp.
 
Pharmacokinetics. In 5 min. after intravenous (in/in) introductions of 2 g of a sulbaktama/tsefoperazon (1 g of a sulbaktam, 1 g of a tsefoperazon) in blood serum the maximum concentration of a sulbaktam and tsefoperazon averaging 130,2 and 236,8 mkg/ml, respectively are reached.

Both components of drug are well distributed in various fabrics and liquids of an organism, including skin and soft tissues, a peritoneum, bile, a wall of a gall bladder, skin, an appendix, pipe fallopiyeva, ovaries, a myometrium, etc. For a sulbaktam higher volume of distribution (l Vd=18.0-27.6) in comparison with that is characteristic of a tsefoperazon (l Vd=10.2-11.3).

Data on existence of any pharmacokinetic interaction between sulbaktamy and tsefoperazony, appointed together, no. At administration of drug each 8-12 h significant changes of pharmacokinetics of both components of a tsefoperazona/sulbaktam it is noted; the effect of cumulation was not observed.

Sulbaktam is brought, generally kidneys - about 84% of a vvedennoydoza are excreted with urine within the first 8 hours.

Tsefoperazon is brought preferential through intestines (about 80%). The maximum concentration of a tsefoperazon in bile are reached between the first and third hours after introduction and more, than by 100 times exceed serumal. The rest of a tsefoperazon is excreted by kidneys (20-30% of the entered dose).

The elimination half-life (Т½) of a sulbaktam at adults with normal function of a liver and kidneys averages about 1 h, a tsefoperazon - 1,7-2 h. At the patients having diseases of a liver and/or obstruction of bilious ways, the elimination half-life of a tsefoperazon is usually extended; at the same time, drug excretion kidneys increases. 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.
 
Essential changes of pharmacokinetics of a tsefoperazon at patients with a renal failure are not revealed. Considerable lengthening Т½ of a sulbaktam (from 6,9 to 9,7 h) is revealed at patients with a heavy and terminal renal failure. The hemodialysis caused considerable changes Т½, the general clearance and volume of distribution of a sulbaktam.

Both components of drug in small concentration are allocated with breast milk.

At elderly people with the accompanying age disturbances of functions of kidneys and a liver increase Т½, decrease in clearance and increase in volume of distribution both a sulbaktam, and tsefoperazon is revealed.

The pharmacokinetics of a sulbaktama/tsefoperazon at children significantly does not differ in comparison with that at adults. Т½ the sulbaktama makes from 0,91 to 1,42 h, a tsefoperazon - from 1,44 to 1,88 h.

Indications to use:

Treatment of the infections caused by sensitive microorganisms:
- infections of upper and lower respiratory tracts, including pneumonia, a pleura empyema, abscess of lungs;
- bacterial meningitis;
- the uncomplicated and complicated infections of abdominal organs, including cholecystitis, a cholangitis, peritonitis, abscess of an abdominal cavity;
- infectious and inflammatory diseases of bodies of a small pelvis (endometritis, salpingo-oophoritis, pelviperitonitis);
- infections of urinary tract (pyelitis, pyelonephritis);
- the infections of skin and soft tissues caused by the mixed aerobic-anaerobic flora;
- septicaemia;
- infections of bones and joints;
- gonorrhea.

Route of administration and doses:

Intravenously and intramusculary. To treatment of heavy infections in/in a way of introduction it is preferable.

Adults and children are more senior than 12 years: on 1-2 g ^{of Sulperatsefa®} (respectively, 0,5-1 g of a tsefoperazon and 0,5-1 g of a sulbaktam) each 12 hours.

At heavy, life-threatening infections - on 4 g (2 g of a tsefoperazon and 2 g of a sulbaktam) in each 12 hours.

The maximum daily dose of a sulbaktam should not exceed 4 g.

Additional introduction of a tsefoperazon can be required by the patients receiving drug in the ratio 1:1.

Dose adjustment is required from patients with the expressed renal failure. At clearance of creatinine of 15-30 ml/min. ^{of Sulperatsef®} each 12 h enter 1 g; at clearance of creatinine less than 15 ml/min. - on 0,5 g each 12 h. At heavy infections additional introduction of a tsefoperazon can be required. At the patients who are on a hemodialysis, ^{Sulperatsef®} enter at once upon termination of dialysis session.

Change of a dose at an abnormal liver function can be required only in cases of heavy obstruction of bilious ways and a serious illness of a liver, and also at patients with a combination of a liver and renal failure. In these cases monitoring of serumal concentration of a tsefoperazon and correction of its dose in case of need is recommended. If regular monitoring of serumal concentration of a tsefoperazon is impossible, then its daily dose should not exceed 2 g.

At children from 1 month to 12 years the daily dose ^{of Sulperatsefa®} makes 40-80 mg/kg which is divided into 2-4 bucketed introductions of 6-12 h. For treatment of heavy infections the dose is increased to 160 mg/kg a day.

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

Rules of preparation of solutions. For preparation of solution for in/in jet introductions of 0,5 and 1 g ^{of Sulperatsefa®} dissolve in 10 ml, and 2 g - in 20 ml of water for injections or 0,9% of solution of sodium of chloride. Enter in/in slowly, within 3-5 min.; introduction through a node for injections (in "elastic band") systems for intravenous infusions at transfusion of compatible solutions is possible.

For in drop infusion of 0,5 and 1 g ^{of Sulperatsefa®} dissolve in 10-20 ml of sterile water for injections or 0,9% of solution of sodium of chloride; after full dissolution the received solution add 0,9% of solution of sodium of chloride or 5% of solution of a dextrose to 50-100 ml; enter intravenously kapelno, using system for intravenous infusions.

For introduction in oil it is possible to use 2% hydrochloride lidocaine solution (in the absence of an allergy to local anesthetics!), but it cannot be applied to primary cultivation of powder. Therefore, solution is prepared in two stages. For primary cultivation use sterile water for injections in the quantities provided below:

	0,5 g of Sulperatsefa®	1,5 ml
	1,0 g of Sulperatsefa®	2,4 ml
	2,0 g of Sulperatsefa®	4,7 ml

Then the received solution is dissolved by 2% with lidocaine solution, adding 0,5 ml, 1 ml and 2 ml of local anesthetic to the solution received at primary cultivation containing 0,5 g, 1 g or 2 g ^{of Sulperatsefa®}, respectively, to receive antibiotic solution in 0,5% hydrochloride lidocaine solution.

Enter deeply intramusculary into body parts with the expressed muscular layer (for example, an upper-outside quadrant of a buttock).

Features of use:

Сульперацеф® it is used as the only antibiotic (monotherapy) for treatment of the mixed aerobic-anaerobic infections of the most various localizations including caused by strains of the bacteria steady against penicillin, other cephalosporins, linkozamida, ftorkhinolona and aminoglycosides.

At heavy obstruction of bilious ways, a serious illness of a liver, and also the renal failures which are combined with any of the specified states correction of the mode of a drug dosing can be required.

At treatment tsefoperazony (as well as at use of other antibiotics) deficit of vitamin K, apparently, owing to suppression of normal intestinal microflora which synthesizes this vitamin in rare instances develops. 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 in artificial nutrition At such patients control of a prothrombin time has to be exercised; in case of need appoint vitamin K. Similar control needs to be exercised at patients who receive therapy by anticoagulants.

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

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

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.

Side effects:

From the alimentary system: nausea, vomiting, diarrhea, pseudomembranous coloenteritis.

From system of blood: leukopenia, neutropenia, decrease in level of hemoglobin and hematocrit, thrombocytopenia, eosinophilia, false positive test of Koombs.

Laboratory indicators: tranzitorny increase in activity of alaninaminotranspherase and asparaginaminotransferaza, alkaline phosphatase, increase in serumal bilirubin.

Allergic reactions: small tortoiseshell, dermahemia, skin itch, Quincke's disease, acute anaphylaxis, Stephens-Johnson's syndrome.

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

Others: headache, fever, fever.

Interaction with other medicines:

Similar to Disulfiramum, causes intolerance of ethanol. At alcohol intake during treatment of Sulperatsefom® the reactions which are characterized by inflows, perspiration, a headache and tachycardia are possible. Therefore, it is necessary to refrain from the use of alcoholic beverages in time and up to 5 days after completion of treatment by drug. At patients who need artificial nutrition (inside or parenterally) it is necessary to avoid use of the solutions containing ethanol.

At simultaneous use with aminoglycosides a synergism of bactericidal action concerning gram-positive and gram-negative bacteria is observed.

Pharmaceutical it is incompatible with products of blood and proteinaceous hydrolyzates, aminoglycosides. If the combination therapy of Sulperatsefom® and aminoglycosides is carried out, they should not be mixed in one syringe or one infusional environment; at introduction in oil to enter into different body parts; at intravenous administration to enter separately, observing a certain sequence with as it is possible a big time interval between injections (infusions), or to use separate intravenous catheters.
It is not necessary to use laktirovanny solution of Ringer for initial dissolution of powder, considering their incompatibility. However compatibility can achieve by two-stage preparation of solution - originally the powder Sulperatsefa® is dissolved in water for injections (2 g of drug dissolve in about 7 ml of water for injections for receiving the solution containing to sulbakta in concentration of 125 mg/ml), and then part with laktirovanny solution of Ringer with a lactate to concentration of a sulbaktam 5 mg/ml.

Contraindications:

Hypersensitivity to a sulbaktam, a tsefoperazon, other cephalosporins, penicillin.

With care: at patients with a renal and liver failure.

Drug is used only according to strict indications if the expected advantage for mother exceeds potential risk for a fruit.

Overdose:

Symptoms: it is possible to expect manifestation of the undesirable effects registered when using drug; high concentration beta лактамных antibiotics in cerebrospinal liquid can lead to neurologic disturbances, including spasms.

Treatment: symptomatic and maintenance therapy. In hard cases - a hemodialysis, especially in case of overdose at patients with an impaired renal function.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

250 mg +250mg; 500 mg +500mg; 1,0 g +1,0 g of a sulperatsef in bottles glass with a capacity of 10 ml and 20 ml.
1 bottle with drug and the application instruction is placed in a pack from a cardboard. Solvent - "Water for injections" in glass ampoules of 5 ml.
1 bottle with drug and the application instruction is placed in a pack from a cardboard.

1 bottle with drug and 1 ampoule with solvent is packed into a blister strip packaging. One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug pack into blister strip packagings. One blister strip packaging and the application instruction are put in a pack cardboard.

5 bottles with drug complete with 5 ampoules of solvent pack into blister strip packagings. One blister strip packaging with drug, one blister strip packaging with solvent and the application instruction is put in a pack cardboard.