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Cefoperazone + sulbactam

Cefoperazone + sulbactam

International Nonproprietary Name:

Cefoperazone, sulbactam

Pharmaceutical form:

Injection solution preparation powder.
  • Properties

    Pharmacological properties:

    Antibacterial component of the drug is cefoperazone - cephalosporin of the third generation, which acts bactericidal, by inhibiting the synthesis of the bacterial wall.  Sulbactam has no real antibacterial activity besides action against Neisseriaceae and Acinetobacter,though it is an inhibitor of beta-lactamase enzymes, which are produced by microorganisms resistant to beta-lactam antibiotics.

    Sulbactam prevents the destruction of penicillins and cephalosporins by resistant microorganisms and demonstrates pronounced synergism with penicillins and cephalosporins.  Since sulbactam also binds to certain penicillin-binding proteins, sensitive microorganisms become more susceptible to the action of sulbactam / cefoperazone than to the effect of a single cefoperazone.

    The combination of sulbactam and cefoperazone is active against such microorganisms: Haemophilus influenzae, species of Bacteroides, Acinetabacter calcoaceticus, Enterobacter aerogens, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.

    Sulbactam / cefoperazone develops in vitro activity against a wide range of clinically relevant microorganisms.

    Gram-positive microorganisms: Staphylococcus aureus (including strains producing and not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae (mainly Diplococcus pneumoniae), Streptococcus pyogenes (group A beta beta-hemolytic streptococcus), Streptococcus agalactiae (group B beta-hemolytic streptococcus), most other types of beta Hemolytic streptococci, many types of Streptococcus faecalis.

    Gram-negative microorganisms: Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii (predominantly Proteus morganii), Providencia rettgeri (predominantly Proteus rettgeri), Providencia species, Serratia species (including S. marcescens) Salmonella and Shigella, Pseudomonas aeruginosa, certain species of Pseudomonas, Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica.

    Anaerobic microorganisms: Gram-negative bacilli (including Bacteroides fragilis, other species of Bacteroides and species of Fusobacterium); Gram-positive and gram-negative cocci (including species of Peptococcus, Peptostreptococcus and Veillonella); Grampositive bacilli (including species of Clostridium, Eubacterium and Lactobacillus).

    Pharmacokinetics

     

    Absorption

    After intravenous (iv) administration of 1 g of cefoperazone, the maximum concentration (Cmax) is reached after 30 minutes and is 114 μg / ml.  After IV administration, 500 mg or 1 g of Sulbactam Cmax is reached after 15 minutes and is 21-40 μg / ml and 48-88 μg / ml, respectively.

    Allocation

    The binding with plasma proteins of cefoperazone is 82-93%, sulbactam -38%.

    Mean values of the maximum concentrations of sulbactam and cefoperazone after administration of 2 g of sulbactam / cefoperazone intravenously for 5 minutes are 130.2 and 236.8 μg / ml.  This indicates a greater volume of distribution of sulbactam (Vα = 18,0-27,6 L) compared with the distribution of cefoperazone (Vα = 10,2-11,3 L).

    Both sulbactam and cefoperazone are subject to intensive distribution in tissues and body fluids, including bile, gall bladder, skin, appendix, fallopian tubes, ovaries, uterus and others.

    Excretion

    With the administration of the drug, approximately 84% of the dose of sulbactam and 25% of the dose of cefoperazone obtained by the kidneys. Most of the dose of cefoperazone is excreted with bile. After the administration of sulbactam / cefoperazone, the average T1 / 2 sulbactam is 1 hour, and cefoperazone is 1.7 hours. Concentrations in the plasma are proportional to the administered dose.

    In children, the average term of T1/ 2 sulbactam ranges from 0.91 to 1.42 hours, and cefoperazone is between 1.44 and 1.88 hours.

    Data on any pharmacokinetic interaction between sulbactam and cefoperazone when combined in the form of a complex preparation are not available.

    After repeated administration, no significant changes were observed in the pharmacokinetics of the sulbactam / cefoperazone components and any cumulation thereof every 8-12 hours.

  • Indications

    • infection of the upper and lower divisions of the respiratory tract (including bacterial sinusitis);

    • infections of the upper and lower parts of the urinary tract;

    • infection of the abdominal cavity (including peritonitis, cholecystitis, cholangitis);

    • infection of skin and soft tissues;

    • infection of bones and joints;

    • infection of the small pelvis (including endometritis);

    • gonorrhea;

    • septicemia;

    • meningitis

  • Contraindications

    Hypersensitivity to cefalosporins and other β-lactam antibiotics.

    Administartion of the drug during pregnancy and lactation (breastfeeding) is possible only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.

  • Dosage and Administration

    Cephoperazone + sulbactam is intended for intravenous and intramuscular administration. Before staring the therapy, it is necessary to exclude the presence of hypersensitivity in the patient, trying a skin test.

    Adult use. The recommended daily dose of Cefoperazone + sulbactam is 2-4 g. The drug should be administered every 12 hours in a uniformly distributed dose. In severe or refractory infections, the daily dose of the drug can be increased to 8 g.

    Patients who receive the drug may need additional prescription of cefoperazone (should be injected every 12 hours in a uniformly distributed dose). The maximum daily dose of sulbactam is 4 g.

    Administration in case of impaired liver function.  Dose adjustment may be necessary in cases of severe obstructive jaundice and severe liver disease, or for pathologies are accompanied by impaired renal function.  In patients with impaired hepatic function and concomitant renal dysfunction, control of cefoperazone concentration in the plasma and, if necessary, appropriate dose adjustment, are necessary. In the absence of careful monitoring of the concentration of the drug in plasma, the dose of cefpoperazone should not exceed 2 g per day.

    Application for violations of kidney function. When applying the drug Cefoperazone + sulbactam in patients with creatinine clearance less than 30 ml / min, a dose adjustment is necessary to compensate for the reduced clearance of sulbactam. With a creatinine clearance of 15-30 ml / min, the maximum single dose of sulbactam is 1 g every 12 hours; When creatinine clearance is less than 15 ml / min - 500 mg every 12 hours.  Therefore, in severe infections, it may be necessary to prescribe cefoperazone.

    When using dialysis, correction of the dose regimen is necessary (see.  Application features)  

    Pediatric use.  The recommended daily dose of Cefoperazone + sulbactam is 40-80 mg / kg body weight. The drug should be injected every 6-12 hours in evenly distributed doses. In severe or refractory infections, the daily dose of Cefoperazone + sulbactam can be increased to 160 mg / kg and divided into 2-4 equal doses.

    Infants of the first week of life should be given the drug every 12 hours.  The maximum daily dose for infants should not exceed 80 mg / kg.

    Intravenous use. For drip infusion, the contents of 1 bottle (2.0 g) should be dissolved in 6-7 ml of 5% glucose solution in water, 0.9% sodium chloride solution or sterile water for injection, and then diluted to 20 ml with the same solvent. The drug is administered infusion for 15-30 minutes. 

    Cephoperazone + sulbactam is compatible with water for injection, 5% glucose solution in 0.225% sodium chloride solution, 5% glucose solution in 0.9% sodium chloride solution in concentrations from 10 mg / ml cephoperazone and 10 mg / ml sulbactam to 250 mg / ml cefoperazone and 250 mg / ml sulbactam.

    Ringer's lactate solution is suitable for dilution with intravenous infusion, but not for primary dilution.

    For intravenous injection, the contents of the vial should be dissolved as described above and administered for 3 minutes minimum.

    Intramuscular use. A lidocaine solution is suitable for dilution when administered intramuscularly, but not for primary dissolution.

    After dissolution, it is possible to store the solution for IM and IV or the administration of the drugw at a temperature of 8 ° to 25 ° C for 24 hours, at a temperature of 2 ° to 8 ° C-7 days. 

    It is forbidden to dilute with novocaine!
  • Drug form
    Powder for the preparation of injection solution in bottles of 1.0 g and 2.0 grams