Active substanceCefoperazoneCefoperazone
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  • Dosage form: & nbspPowder for the preparation of solution for intravenous and intramuscular injection.
    Composition:
    Active substance: Cefoperazone sodium in terms of cefoperazone - 1.0 g.

    Description:White or white with a yellowish tint powder. Hygroscopic.
    Pharmacotherapeutic group:Antibiotic-cephalosporin.
    ATX: & nbsp

    J.01.D.D.12   Cefoperazone

    Pharmacodynamics:

    Semisynthetic cephalosporin antibiotic III generation of a broad spectrum of antibacterial action. Has a bactericidal effect due to inhibition of bacterial cell wall synthesis.

    Active in vitro for a large number of clinically relevant microorganisms. Resistant to the action of many beta-lactamases.

    The following microorganisms are sensitive to cefoperazone: Gram-positive - Staphylococcus aureus (strains producing and not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic group streptococcus A), Streptococcus agalactiae (beta-hemolytic streptococcus group B), Enterococcus (Streptococcus faecalis, S. faecium and S. durans);.rpa- matrices - Escherichia coli, Klebsiella species (including K. pneumoniae), Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia stuartii, Providencia, rettgeri,. Serratia marcescens, Pseudomonas aeruginosa, Pseudomonas spp., some strains Acinetobacter calcoaceticus, Neisseria gonorrhoeae; anaerobic microorganisms: gram-positive cocci (including Peptococcus spp., Peptostreptococcus spp.), Clostridium spp., Bacteroides fragilis and other strains Bacteroides spp. Cefoperazone is also active in vitro for a wide range of other pathogens, however, the clinical significance of this is unknown: Salmonella spp. and Shigella spp., Serratia liquefaciens, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica, Clostridium difficile, Fusobacterium spp., Eubacterium spp. and strains Haemophilus influenzae and Neisseria gonorrhoeae, producing beta-lactamases.

    Pharmacokinetics:The connection with plasma proteins is 82-93%. The time to reach the maximum concentration after intramuscular injection is 1-2 hours, after intravenous injection at the end of the infusion, the maximum concentration after intramuscular administration of 1 and 2 g is 65-75 and 97 μg / ml, respectively; after a single intravenous injection of 1, 2, 3 and 4 g, the maximum concentration is 153, 252, 340 and 506 μg / ml, respectively. The maximum concentration in the urine after intramuscular and intravenous administration is 2 g - 1 and more than 2.2 mg / ml, respectively. Achieves therapeutic concentrations in such tissues and body fluids as peritoneal, ascitic fluid and cerebrospinal fluid (with meningitis), urine, bile, gallbladder walls, lungs, sputum, palatine tonsils and sinus mucosa, atria, kidneys, ureters, prostate, testicles, uterus, fallopian tubes, bones, cord blood and amniotic fluid. The volume of distribution is 0.14-2 l / kg; The half-life is -1.6-2.4 hours; regardless of the mode of administration, 2.8-4.2 hours for hemodialysis, 2.2 hours for newborns and children from 2 months to 11 years. It is excreted with bile - 70-80%, kidneys - 20-30% unchanged. In patients with impaired liver function and bile duct obstruction, the elimination half-life is 3-7 hours, kidney removal is 90% or more.Even with severe liver damage, therapeutic concentrations are achieved in the bile; and the half-life is prolonged only 2-4 times. In patients with renal-hepatic insufficiency can cumulate.
    Indications:
    Infectious-inflammatory diseases caused by microorganisms sensitive to cefoperazone: bacterial infections of the upper and lower respiratory tract, pneumonia, including nosocomial infections, urinary tract infections, intra-abdominal infections (peritonitis, cholecystitis, cholangitis), septicemia, meningitis, skin and soft tissue infections, infection of bones and joints, infectious and inflammatory diseases of the pelvic organs (endometritis, gonorrhea).
    Prevention of infectious complications after abdominal, gynecological and orthopedic operations, as well as in cardiovascular surgery.
    Contraindications:Hypersensitivity to cefoperazone, other beta-lactam antibiotics.
    Carefully:Renal and hepatic insufficiency, colitis in history, children under 1 year old, bile duct obstruction.
    Pregnancy and lactation:
    Cefoperazone penetrates the placental barrier, is excreted in breast milk in small amounts.
    The application is only possible if the potential benefit to the mother exceeds the potential risk to the fetus and the baby.
    When using the drug during lactation, breastfeeding should be discontinued.
    Dosing and Administration:
    Intramuscularly and intravenously (slowly struino or drip).
    The drug is injected deep inside the large gluteus muscle or the anterior surface of the thigh.
    With intravenous slow jet injection, the maximum single dose is 2 g; duration of administration - at least 3-5 minutes. Duration of intravenous injectionpelvic administration - 15-60 minutes. The dose for adults is 2-4 g / day, divided into 2 injections (every 12 hours). In severe infections, the dose can be increased to 8 g / day, divided into 2 injections (every 12 hours). Treatment with the drug can begin before the results of a study of the sensitivity of microorganisms. In uncomplicated gonococcal urethritis - once intramuscularly at a dose of 500 mg. Prevention of postoperative complications: 1 g or 2 g intravenously for 30-90 minutes before the operation, followed by repeated administration every 12 hours (in most cases within 24 hours).

    In operations with an increased risk of infection (eg, operations in the colorectal area), in open-heart surgery or joint replacement, preventive use may continue for up to 72 hours after the completion of the operation.

    Dose correction may be required in cases of severe obstruction of the biliary tract, severe liver disease, or with concurrent liver and kidney dysfunction. In this case, the daily dose should not exceed 2 g. Since cefoperazone basically it is deduced with bile, then correction of the dose in violation of kidney function when used in recommended doses (2-4 g / day) is not required. At a glomerular filtration rate of less than 18 ml / min or a serum creatinine concentration greater than 3.5 mg / dl, the daily dose should not exceed 4 g.

    When hemodialysis, the half-life of cefoperazone from the blood serum decreases slightly, so the drug should be administered after the end of the dialysis session. It is recommended to monitor the concentration of cefoperazone in the blood serum (assuming that the daily dose is more than 2 g) with a combined disturbance of liver and kidney function and, if necessary, adjust the dose.

    The dose for children is 50-200 mg / kg / day, divided into equal parts, administered every 8-12 hours. The maximum dose is 12 g / day. With intravenous slow jet injection. the maximum single dose is 50 mg / kg; duration of administration - at least 3-5 minutes. Newborns (aged less than 8 days) - 50-200 mg / kg / day in equal parts every 12 hours.

    In the treatment of infections caused by Streptococcus pyogenes, in adults and children, the duration of therapy should be at least 10 days.

    Preparation of solutions for intravenous and intramuscular administration.

    Intravenous administration

    Intravenous intravenous injection. The contents of the vial (1 g of cefoperazone) are dissolved first in 2.8 ml of the solvent for intravenous administration. To facilitate dissolution, 5 ml of solvent per g of cefoperazone is recommended. For the initial dilution the following solutions are used:-5% dextrose injection, 10% dextrose injection, 0.9% sodium chloride solution for injection, 5% dextrose solution and 0.9% sodium chloride solution for injection, 5% dextrose solution and 0.2% sodium solution chloride for injection, sterile water for injections.

    After adding the solvent, the contents of the vial are shaken well until completely dissolved.

    Then the whole solution should be diluted in 5-10 ml of one of the following solvents for intravenous administration: 5% dextrose injection, 10% dextrose injection, 5% dextrose solution and Ringer's lactated solution for injection, Ringer's lactated solution, 5 % dextrose solution and 0.9% sodium chloride solution for injection, 0.9% sodium chloride solution for injection.

    Drip intravenous. The contents of the vial (1 g of cefoperazone) are dissolved in 20-100 ml of the solvent for intravenous administration. If the solvent is used water for injections, then no more than 20 ml is added to the vial with the drug.

    Intramuscular injection. For the preparation of solutions intended for intramuscular injection, sterile water for injections. In the cases, when it is intended to administer the drug at a concentration in excess of 250 mg / ml, a 2% solution of lidocaine is recommended for solution preparation. The following two-step dilution method is recommended: to achieve a concentration of cefoperazone 250 mg / ml in a vial containing 1 g of cefoperazone, add 2.6 ml of water for injection, agitate until complete dissolution of the preparation, and then add 0.9 ml of a 2% solution of lidocaine.The final volume will be 4 ml. To achieve a cefoperazone concentration of 333 mg / ml, 1.8 ml of water for injection is added to a vial containing 1 g of cefoperazone, agitated until the drug is completely dissolved, and then 0.6 ml of a 2% solution of lidocaine is added. The final volume will be 3 ml.

    Side effects:

    Allergic reactions: including itching of the skin, maculopapular rash, urticaria, eosinophilia and drug fever, Stevens-Johnson syndrome; anaphylactoid reactions (including shock). The risk of developing allergic reactions is increased in patients with a tendency to allergic reactions (especially penicillin) in the anamnesis.

    From the hematopoiesis: reversible neutropenia (with long-term treatment), false positive Coombs direct test, reduced hemoglobin or hematocrit, eosinophilia and hypoprothrombinemia, bleeding;

    From the side of the digestive system: diarrhea or loosening of the stool, nausea, vomiting, moderate transient increase in activity of alanine aminotransferase, asparagine aminotransferase and alkaline phosphatase, pseudomembranous colitis.

    Local reactions: soreness (with intramuscular injection, injection), phlebitis in place withining injection.

    Overdose:
    Symptoms: neurological disorders, including convulsions.
    Treatment: symptomatic therapy. Hemodialysis is effective.
    Interaction:
    Pharmaceutically incompatible with aminoglycosides (if necessary combined therapy with cefoperazone and aminoglycoside is prescribed as a sequential fractional intravenous drug administration using 2 separate intravenous catheters).
    Aminoglycosides and looped diuretics increase the risk of developing nephrotoxicity, especially in individuals with renal insufficiency.
    Drugs that reduce tubular secretion, increase the concentration of the drug in the blood and slow its elimination.
    When combined with ethanol, disulfiram-like reactions are possible.
    Special instructions:Before treatment it is necessary to collect a detailed allergological anamnesis in order to identify the patient's hypersensitivity to cephalosporins, penicillins and other medicines. If an allergic reaction occurs during treatment, cefoperazone should be discontinued and appropriate treatment initiated. Cefoperazone is largely excreted with bile. In patients with liver disease or obstruction of the biliary tract, the half-life of cefoperazone from the blood plasma is usually prolonged, and the excretion of the drug by the kidneys increases. Nevertheless, even with severe violations of liver function in bile, the therapeutic concentrations of cefoperazone are reached, and the half-life is prolonged only by 2- to 4-fold. In some patients, treatment with cefoperazone may lead to vitamin K deficiency in the body, which is due to the suppression of the intestinal flora that synthesizes this vitamin. The greatest risk is for patients with malabsorption syndrome (for example, in cystic fibrosis), as well as patients who adhere to a defective diet or who are for a long time on parenteral nutrition. In such patients during the treatment period, prothrombin time should be monitored and, if necessary, vitamin K. If prolonged therapy is recommended, periodically monitor the kidneys, liver and hematopoiesis. This is especially important for newborns, especially premature and small children.Clostrifium difficile associated diarrhea is observed against the background of almost all antibacterial drugs, including cefoperazone, and is manifested from mild forms of diarrhea to severe colitis with a fatal outcome. Treatment with antibacterial drugs leads to disruption of normal colon microflora, resulting in increased growth of Clostrifium difficile, producing toxins A and B, which lead to the development of Clostrifium difficile associated diarrhea. Hypertoxin-producing strains of Clostrifium difficile lead to an increase in morbidity and mortality, as they may be resistant to ongoing antibiotic therapy. All cases of diarrhea in patients with antibiotic therapy should be considered as suspicious for the development of Clostrifium difficile associated diarrhea. During treatment, a false positive reaction to glucose in the urine is possible, while conducting a study using solutions of Benedict or Felling. If it is necessary to use the drug in newborns, including preterm infants, the expected positive effects of therapy and the possible risk associated with treatment should be taken into account. In newborns with nuclear jaundice cefoperazone Do not displace bilirubin from the connection with plasma proteins.
    Effect on the ability to drive transp. cf. and fur:During the treatment period, care should be taken when driving vehicles and engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions.
    Form release / dosage:
    Powder for the preparation of solution for intravenous and intramuscular injection.
    Packaging:
    By 1.0 g of active substance into glass bottles with a capacity of 10 ml, hermetically sealed with stoppers made of rubber compound, crimped with aluminum caps or caps combined.
    Vials with a drug of 50 pieces are placed in boxes of cardboard with an equal number of instructions for the use of the drug (for hospitals).
    1 bottle with the drug and instructions for use are placed in a pack of cardboard.
    Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.
    Shelf life:2 years. Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LS-002116
    Date of registration:18.10.2011
    The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia
    Manufacturer: & nbsp
    Information update date: & nbsp26.10.2015
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