Цефоперабол®

General characteristics. Structure:

Active ingredient: 0,5 g, 1,0 g, 2,0 g of a tsefoperazon of sodium salt (in terms of цефоперазон).
 
Tsefalosporinovy antibiotic of the III generation for parenteral administration. Works bakteritsidno, breaking synthesis of a cell wall of microorganisms. Possesses a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the III generation for parenteral administration. Works bakteritsidno, breaking synthesis of a cell wall of microorganisms. Possesses a broad spectrum of activity.

It is active concerning gram-positive microorganisms - Staphylococcus aureus and Staphylococcus epidermidis (the strains which are producing and not producing a penicillinase), Streptococcus pneumoniae, Streptococcus pyogenes (a beta and hemolitic streptococcus of group A), Streptococcus agalactiae (a beta and hemolitic strain of group B), Enterococcus faecalis, many other strains of beta and hemolitic Streptococcus spp.; gram-negative microorganisms - Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae), Enterobacter spp., Citrobacter spp., Haemophilus influenzae (the strains which are producing and not producing beta lactamelements), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Providencia spp, Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., many strains of Pseudomonas aeruginosa and Pseudomonas of other types, some strains of Acinetobacter spp. Neisseria gonorrhoeae (the strains which are producing and not producing beta lactamelements), Neisseria meningitides, Bordetella pertussis, Yersinia enterocolitica; anaerobic microorganisms - gram-positive and gram-negative cocci (including Peptococcus, Peptostreptococcus and Veilloneilla spp.), gram-positive sporo-and asporous anaerobe bacterias (Clostridium spp., Eubacterium spp., Lactobacillus spp.) and gram-negative anaerobe bacterias (including Fusobacterium spp., many strains of Bacteroides fragilis and others of Bacteroides spp strains., Prevotella spp.).

Pharmacokinetics. Communication with proteins of plasma - 82-93%. Time of achievement of the maximum concentration (Tmax) after intramuscular introduction - 1-2 h, after intravenous - at the end of infusion. The maximum concentration (Cmax) in serum after intramuscular introduction (1 g) - 65-75 mkg/ml, after single intravenous administration (1 g) - 153 mkg/ml. Cmax in urine after intramuscular and intravenous administration (1 g) - 1000 mkg/ml.

Reaches therapeutic concentration in fabrics and liquids of an organism: peritoneal, ascitic liquid and cerebrospinal fluid (at meningitis), urine, bile, walls of a gall bladder, lungs, a phlegm, palatine tonsils and a mucous membrane of sine, auricles, kidneys, ureters, a prostate, testicles, a uterus, fallopiyeva of a pipe, a bone, blood of an umbilical cord and amniotic liquid.

The volume of distribution is 0,14-2,0 l/kg. The elimination half-life (Т½) - 1,6-2,4 h, irrespective of a way of introduction, 2,8-4,2 h at a hemodialysis, 2,2 h - at newborns and children of 2 months is 11 years. It is removed with bile - 70-80%, kidneys - 20-30% in not changed look. At patients with the broken function of a liver and obstruction of biliary tract Т½ - 3-7 h, removal with urine - 90% and more. Even at severe damages of a liver in bile therapeutic concentration are reached, and Т½ it is extended only by 2-4 times.
 
At patients with a renal and liver failure can kumulirovat.

Indications to use:

- bacterial infections of upper and lower respiratory tracts;
- infections of urinary tract;
- abdominal infections (peritonitis, cholecystitis, cholangitis, etc.);
- sepsis;
- meningitis;
- infections of skin and soft tissues;
- infections of bones and joints;
- infectious and inflammatory diseases of bodies of a small pelvis (including endometritis);
- gonorrhea and other infections of a genital tract;
- prevention of infectious complications at abdominal, gynecologic, cardiovascular and orthopedic operations.

Route of administration and doses:

Intravenously and intramusculary. The adult - in the average daily dose of 2-4 g divided into 2 introductions with an interval of 12 h. At the heavy course of infections the dose can be increased to 12 g a day: on 2-4 g each 8 h, or 3-6 g each 12 h. Treatment can be begun before obtaining results of a research of sensitivity of microorganisms. At an uncomplicated gonococcal urethritis - once intramusculary in a dose of 500 mg.

Prevention of postoperative complications: on 1 g or 2 g in/in in 30-60 min. prior to operation, with the subsequent repeated introduction each 12 h (in most cases during no more than 24 h). At operations with the increased risk of infection (for example, operations in colorectal area), at open heart operations or prosthetics of joints preventive use can continue during 72 h after completion of operation.
Patients with a glomerular filtration rate is lower than 18 have some, or creatinine it is higher than 3,5 mg/dl - no more than 4 g a day. Patients with hepatonephric insufficiency have no more than 2 g a day. At the isolated liver failure of a dose decline it is not required if the patient does not receive the maximum dose since renal excretion of drug kompensatorno increases up to 90% and more.

Children - in daily doses have from 50 to 200 mg/kg in 2-3 receptions (each 8-12 h); the newborn (less than 8 days) the daily dose of 50-200 mg/kg is divided into 2 receptions and each 12 h enter.

At children of early age and children with heavy infections, including bacterial meningitis, daily doses, up to 300 mg/kg, are applied without complications.

Rules of preparation of solution and introduction.
Intramuscular introduction. For preparation of solutions for intramuscular introduction the following solvents can be used:
  - water for injections;
  - 0,9% chloride sodium solution;
which add to 1 g of a tsefoperazon of 3 ml. At hydrochloride lidocaine use (in the absence of an allergy to local anesthetics!) solution is prepared in two stages: for primary cultivation add water for injections in the quantities provided below to 1 g of a tsefoperazon and stir up a bottle before full dissolution of powder; add the necessary number of 2% of solution of lidocaine of a hydrochloride to the received solution and mix. Approximate concentration of lidocaine in ready solution - 0,5%.

	1 stage: water volume for  injections	2 stage: volume is 2% of solution  lidocaine
for receiving solution tsefoperazona of 250 mg/l	2,6 ml	0,9 ml
for receiving solution tsefoperazona of 330 mg/l	1,8 ml	0,6 ml

The received solution is entered deeply intramusculary into body parts with the expressed muscular layer (an upper outside quadrant of a buttock or the lateral surface of a hip).

Intravenous administration. General recommendations. Contents of a bottle are dissolved in sterile water for injections or in one of the following compatible solutions for in/in introductions:
- 5% dextrose solution;
- 0,9% chloride sodium solution;
- Ringer's solution of a lactate;
- 10% dextrose solution;
- solution Normosol R;
- solution Normosol of M in 5% to a dextrose;
- the aqueous solution containing 0,9% of sodium of chloride and 5% of glucose.

For simplification of dissolution it is recommended to use 5 ml of solvent on 1 g of a tsefoperazon. Then the received solution is in addition dissolved with one of compatible solutions for in/in introductions.

At direct (jet) intravenous administration the maximum single dose of a tsefoperazon for adults makes 2 g, for children of 50 mg/kg of body weight. For preparation of solution for introductions to a bottle with dry powder of an antibiotic (1 g) add 10 ml of water for injections to jet or other compatible solvent. Enter slowly, within 3-5 min.

For drop intravenous administration of 1 g of a tsefoperazon dissolve in 5 ml of sterile water for injections, add the received solution to 20-100 ml of compatible infusion solution. Introduction duration depending on the volume of solution can make 10-30 minutes and more.

Freshly cooked solutions of a tsefoperazon keep the stability within 24 hours at a temperature of 25 °C

Features of use:

It can be applied at a combination therapy in combination with other antibiotics.

At combined use with aminoglycosides it is recommended to control function of kidneys.

The patient with hypersensitivity to penicillin, it is necessary to appoint drug carefully as there is a probability of cross hypersensitivity between penicillin and cephalosporins.

In cases of obturation of bilious channels, a serious illness of a liver or the accompanying renal failure, need for change of the mode of dosing can appear (see the section "Route of Administration and Doses")

Prolonged use can lead to development of stability of activators.

During use of drug false positive reaction to glucose in urine with Benedict or Felinga's solution can take place.

During treatment it is necessary to refrain from ethanol reception - the effects similar to action of Disulfiramum are possible (a dermahemia of the person, spasms in a stomach, nausea, vomiting, a headache, a lowering of arterial pressure, tachycardia, short wind).

The patients adhering to a defective diet or having disturbance of absorption of food (for example, suffering from a mucoviscidosis), and also the patients who are for an appreciable length of time on parenteral food can have a deficit of vitamin K. Control of a prothrombin time has to be exercised by such patient, and if necessary purpose of exogenous vitamin K is shown them.

Цефоперабол® does not influence ability to manage the vehicle or other potentially dangerous mechanisms.

Side effects:

Allergic reactions: urticaria, makulopapulezny rash, fever, eosinophilia, multiformny erythema, malignant exudative erythema (Stephens-Johnson's syndrome), false positive direct test of Koombs.

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

From bodies of a hemopoiesis and system of a hemostasis: tranzitorny anemia, a tranzitorny neutropenia (at prolonged treatment), an eosinophilia, decrease in hemoglobin and a hematocrit, a prothrombinopenia, increase in a prothrombin time.

Laboratory indicators: increase in activity of "hepatic" transaminases and alkaline phosphatase, giperkreatininemiya.

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

Interaction with other medicines:

Let's combine from 5% solution of a dextrose, 10% solution of a dextrose, 0,9% chloride sodium solution, laktirovanny solution of Ringer, solution Normosol of R, solution Normosol of M from 5% the dextrose solution, aqueous solution containing 0,9% of sodium of chloride and 5% of a dextrose.

Pharmaceutical it is incompatible with aminoglycosides (in need of carrying out a combination therapy tsefoperazony and aminoglycoside appoint in the form of consecutive fractional intravenous administration of drugs, or use 2 separate intravenous catheters).

At combined use with ethanol development of disulfiramopodobny reactions is possible.

Indirect anticoagulants, heparin, trombolitik increase risk of emergence of a prothrombinopenia, bleeding.

At combined use with aminoglycosides and "loopback" diuretics the risk of development of nephrotoxicity, especially at persons with a renal failure increases.

The drugs reducing canalicular secretion increase concentration of a tsefoperazon in blood and slow down its removal.

Overdose:

Symptoms: neurologic disturbances, including spasms.
Treatment: sedative therapy using diazepam; the hemodialysis can promote removal of a tsefoperazon from an organism if the overdose happened at the patient to a renal failure.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

On 0,5 g and 1 g in bottles glass with a capacity of 10 ml.

As solvent "Water for injections" in ampoules of 5 ml is used.

- 1 bottle with drug and the application instruction is placed in a pack from a cardboard.

- 1 bottle with drug, 1 ampoule with solvent and the application instruction is packed into a blister strip packaging from the polyvinyl chloride film and aluminum foil varnished or without foil. One planimetric packaging and the application instruction are put in a pack from a cardboard.

- 5 bottles with drug pack into a blister strip packaging from the polyvinyl chloride film and aluminum foil varnished or without foil. One planimetric packaging and the application instruction are put in a pack from a cardboard.

- 5 bottles with drug complete with 5 ampoules of solvent pack into blister strip packagings from the polyvinyl chloride film and aluminum foil varnished or without foil. One planimetric packaging with drug, one planimetric packaging with solvent and the application instruction is put in a pack from a cardboard.