Instructions:
Clinical and pharmacological groups
06.012 (III generation cephalosporin with beta-lactamase inhibitor) 06.010 (III generation cephalosporin)
pharmachologic effect
Broad-spectrum cephalosporin antibiotic of the third generation. It has a bactericidal effect by inhibiting the synthesis of bacterial cell walls. Cefoperazone acetylates membrane-bound transpeptidases, disrupting the cross-linking of peptidoglycans necessary to ensure cell wall strength and rigidity.
Active against aerobic, anaerobic, gram-positive and gram-negative bacteria, as well as against Pseudomonas aeruginosa.
Resistant to most β-lactamases.
Pharmacokinetics
Plasma protein binding is 82-93%. Distributed in tissues and body fluids, reaching Cmax in bile after 1-2 hours. It penetrates poorly through the blood-brain barrier, penetrates the placental barrier, and is excreted in breast milk. Excreted in bile. Up to 30% of the dose is excreted unchanged in the urine within 12-24 hours.
Dosage
Administer intravenously or intramuscularly.
A single dose for intravenous administration for adults is 1-4 g/day, the interval between administrations is 12 hours. Depending on the etiology of the disease, intramuscular administration of 500 mg is possible once.
Children - 50-200 mg/kg/day, frequency of administration - 2 times/day.
The maximum daily dose for adults is 12 g.
Drug interactions
Cefoperazone, by suppressing intestinal flora, prevents the synthesis of vitamin K. Therefore, when administered simultaneously with drugs that reduce platelet aggregation (NSAIDs, salicylates, sulfinpyrazone), the risk of bleeding increases. For the same reason, when used simultaneously with anticoagulants, an increase in the anticoagulant effect is observed.
Use during pregnancy and lactation
Contraindicated for use during pregnancy and lactation (breastfeeding).
Side effects
From the digestive system: nausea, vomiting, diarrhea, transient increase in the activity of liver transaminases, cholestatic jaundice, hepatitis, pseudomembranous colitis.
Allergic reactions: skin rash, itching, eosinophilia; rarely - Quincke's edema.
From the hematopoietic system: with long-term use in high doses, changes in the peripheral blood picture are possible (leukopenia, neutropenia, thrombocytopenia, hemolytic anemia).
From the blood coagulation system: hypoprothrombinemia.
From the urinary system: interstitial nephritis.
Effects due to chemotherapy: candidiasis.
Local reactions: phlebitis (with intravenous administration), pain at the injection site (with intramuscular administration).
Indications
Infectious and inflammatory diseases caused by microorganisms sensitive to cefoperazone, incl. diseases of the upper and lower respiratory tract, infections of the genitourinary system, peritonitis, cholecystitis and other abdominal infections, sepsis, meningitis, infections of the skin and soft tissues, infections of the pelvic organs.
Prevention of infectious complications after abdominal, gynecological, cardiovascular and orthopedic surgeries.
Contraindications
Severe renal failure, pregnancy, lactation, hypersensitivity to cephalosporins and other beta-lactam antibiotics.
special instructions
Cefoperazone is used with caution in case of liver dysfunction (with simultaneous impairment of liver and kidney function, dose adjustment is necessary), as well as in patients with a history of bleeding.
In patients with hypersensitivity to penicillins, allergic reactions to cephalosporin antibiotics are possible.
During the period of use of cefoperazone, a false positive reaction of urine to glucose is possible.
During treatment with cefoperazone, you should avoid drinking alcohol, because it is possible to develop effects similar to those of disulfiram (abdominal cramps, nausea, vomiting, headache, hypotension, shortness of breath, tachycardia).
Preparations containing CEFOPERAZONE
• SULPERACEF® powder for preparation. solution d/iv and i/m injection. 1 g+1 g: fl. 1 or 5 pcs. included with or without solvent • CEFOPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 10 or 50 pcs. • CEFOPERABOL® powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1 or 5 pcs. included with or without solvent • SULCEF powder for preparation. solution for intravenous and intramuscular administration of 1 g+1 g: vial. 1 or 100 pcs. • CEFOPERAZONE & SULBACTAM SPENSER powder for preparation. solution d/iv and i/m injection. 1 g+1 g: fl. 1 PC. • CEFOPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 500 mg: vial. 1, 10, 25 or 50 pcs. • SULZONCEF® powder for preparation. solution for intravenous and intramuscular administration of 1 g+1 g: vial. 1, 5, 10 or 50 pcs. • CEFOPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 10, 25 or 50 pcs. • CEFOPERUS® powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 5 or 10 pcs. • CEFPAR (CEFPAR) powder for preparation. solution for intramuscular and intravenous administration of 2 g: fl. 1 or 50 pcs. • MOVOPERIZ powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 10 pieces. • CEFOPERABOL® powder for preparation. solution for intravenous and intramuscular administration of 500 mg: vial. 1 or 5 pcs. in the computer with or without solvent • CEFOPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 500 mg: vial. 1 PC. • CEFOPERUS® powder for preparation. solution for intravenous and intramuscular administration of 2 g: fl. 1, 5 or 10 pcs. • CEFPAR (CEFPAR) powder for preparation. solution for intramuscular and intravenous administration of 1 g: fl. 1 or 50 pcs. • CEFOBID® (CEFOBID®) powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1 PC. • SULPERACEF® powder for preparation. solution d/iv and intramuscular injection. 500 mg+500 mg: vial. 1 or 5 pcs. included with or without solvent • CEFOPERAZONE-AGIO powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 10 or 50 pcs. • SULCEFAZON powder for preparation. solution for intravenous and intramuscular administration 250 mg + 250 mg: vial. 1, 5, 10 or 50 pcs. • SULMOVER powder for preparation. solution d/iv and intramuscular injection. 1 g+1 g: fl. 1 or 10 pcs. • MEDOCEF powder for preparation. solution for intravenous and intramuscular administration of 2 g: fl. 1, 10, 25, 50 or 100 pcs. • SULCEFAZON powder for preparation. solution for intravenous and intramuscular administration of 500 mg+500 mg: vial. 1, 5, 10 or 50 pcs. • TSEBANEKS (CEBANEX) powder for preparation. solution d/iv and intramuscular injection. 500 mg+500 mg: vial. 1 PC. • CEFPAR (CEFPAR) powder for preparation. solution for intramuscular and intravenous administration 500 mg: vial. 1 or 50 pcs. • MEDOCEF powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 10, 25, 50 or 100 pcs. • BACPERAZONE powder for preparation. solution for intravenous and intramuscular administration 250 mg + 250 mg: vial. 1 PC. • CEFOPERAZONE J powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1, 10, 25, 48 or 100 pcs. • CEPHPAR SV powder for preparation. solution d/iv and intramuscular injection. 500 mg+500 mg: vial. 1 or 50 pcs. • SULPERASON powder for preparation. solution d/v/v and i/m introduced. 1 g+1 g: fl. 1 PC. • CEFOPERABOL® powder for preparation. solution for intravenous and intramuscular administration of 2 g: fl. 1 or 5 pcs. included with or without solvent • CEFOPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 2 g: fl. 1, 10, 25 or 50 pcs. • CEFOPERAZONE & SULBACTAME JODAS powder for preparation. solution d/iv and intramuscular injection. 1 g+1 g: fl. 1 PC. • BACPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 1 g+1 g: vial. 1 PC. • CEFOPERUS® powder for preparation. solution for intravenous and intramuscular administration of 500 mg: vial. 1, 5 or 10 pcs. • CEFOPERAZONE-VIAL powder for preparation. solution for intravenous and intramuscular administration of 1 g: fl. 1 PC. • SULCEFAZON powder for preparation. solution for intravenous and intramuscular administration of 1 g+1 g: vial. 1, 5, 10 or 50 pcs. • OPERAZ powder for preparation. injection solution 1 g: fl. 1 or 100 pcs. • BACPERAZONE powder for preparation. solution for intravenous and intramuscular administration of 500 mg+500 mg: vial. 1 PC. • CEPHPAR SV powder for preparation. solution for intravenous and intramuscular administration of 1 g+1 g: vial. 1 PC. • DARDUM powder for preparation. solution for intramuscular and intravenous administration of 1 g: fl. 1 or 100 pcs. • CEFOPERAZONE J powder for preparation. solution for intravenous and intramuscular administration of 2 g: fl. 1, 10, 25, 48 or 100 pcs. • SULPERACEF® powder for preparation. solution d/iv and intramuscular injection. 250 mg+250 mg: vial. 1 or 5 pcs. included with or without solvent
Cefoperazone
Before treatment, it is necessary to collect a detailed allergic history in order to identify the patient’s hypersensitivity to cephalosporins, penicillins and other drugs. In patients with hypersensitivity to penicillin, the drug should be prescribed with caution due to possible cross-sensitivity. If an allergic reaction occurs during treatment, the use of cefoperazone should be discontinued and appropriate treatment should be initiated.
Cefoperazone is largely excreted in bile. In patients with liver disease or biliary obstruction, T1/2 of cefoperazone from blood plasma is usually prolonged, and renal excretion of the drug is increased. However, even with severe liver dysfunction, therapeutic concentrations of cefoperazone are achieved in the bile, and T1/2 is extended only 2-4 times.
In some patients, treatment with cefoperazone can lead to vitamin K deficiency in the body, which is associated with suppression of the intestinal flora that synthesizes this vitamin. Patients with malabsorption syndrome (for example, cystic fibrosis), as well as patients who adhere to an inadequate diet or are on parenteral nutrition for a long time are at greatest risk. In such patients, prothrombin time should be monitored during treatment and, if necessary, vitamin K should be prescribed.
During long-term therapy, it is recommended to periodically monitor the function of the kidneys, liver and hematopoietic organs. This is especially important for newborns, especially premature and small children.
Clostrifium difficile associated diarrhea is observed with the use of almost all antibacterial drugs, including cefoperazone, and manifests itself from mild forms of diarrhea to severe colitis with a fatal outcome. Treatment with antibacterial drugs leads to disruption of the normal microflora of the colon, resulting in increased growth of Clostrifium difficile, which produces toxins A and B, which lead to the development of Clostrifium difficile associated diarrhea. Hypertoxin-producing strains of Clostrifium difficile lead to increased morbidity and mortality because they may be resistant to antibiotic therapy. All cases of diarrhea in patients during antibiotic therapy should be considered suspicious for the development of Clostrifium difficile associated diarrhea.
During the treatment period, a false positive reaction to glucose in the urine is possible when testing using Benedict's or Fehling's solutions.
If necessary, use in newborns, incl. prematurity, the expected positive effects of therapy and the possible risks associated with treatment should be taken into account.
In newborns with kernicterus, cefoperazone does not displace bilirubin from binding to plasma proteins.
Cefoperazone and Sulbactam for intravenous solution 2g+2g fl N1 (Elf)
Intravenously and intramuscularly. Use in adults. In adults, sulbactam/cefoperazone is recommended for use in the following daily doses. Ratio 1:1. Sulbactam/Cefoperazone 2.0-4.0; Sulbactam dose (g) 1.0-2.0; Cefoperazone dose (g) 1.0-2.0. The daily dose should be divided into equal parts and administered every 12 hours. For severe or refractory infections, the daily dose of sulbactam/cefoperazone can be increased to 8 g with a ratio of the main components of 1:1 (i.e. 4 g of cefoperazone). Patients receiving sulbactam/cefoperazone in a 1:1 ratio may require additional administration of cefoperazone. The dose should be divided into equal parts and administered every 12 hours. The recommended maximum daily dose of sulbactam is 4 g. Use for impaired renal function. In patients with a creatinine clearance of 15-30 ml/min, the maximum dose of sulbactam is 1 g every 12 hours (maximum daily dose of sulbactam 2 g), and in patients with a creatinine clearance of less than 15 ml/min, the maximum dose of sulbactam is 500 mg every 12 hours ( the maximum daily dose of sulbactam is 1 g). For severe infections, additional administration of cefoperazone may be required. The pharmacokinetics of sulbactam changes significantly during hemodialysis. The half-life of cefoperazone from blood serum is slightly reduced during hemodialysis. Therefore, administration of the drug should be planned after dialysis. Use for liver dysfunction. Dose changes may be required in cases of severe biliary obstruction, severe liver disease, and renal dysfunction associated with any of these conditions. In patients with impaired liver function and concomitant impaired renal function, it is necessary to monitor the serum concentration of cefoperazone and adjust its dose if necessary. If the daily dose of cefoperazone does not exceed 2 g, there is no need to monitor its serum concentration. Use in children. In children, sulbactam/cefoperazone is recommended for use in the following daily doses. Ratio 1:1. Sulbactam/Cefoperazone (mg/kg/day) 40-80; Sulbactam dose (mg/kg/day) 20-40; Cefoperazone dose (mg/kg/day) 20-40. The dose should be divided into equal parts and administered every 6-12 hours. For serious or refractory infections, these doses can be increased to 160 mg/kg/day for a 1:1 ratio of the main components. The daily dose is divided into 2-4 equal parts. Use in newborns. In newborns, during the first week of life, the drug should be administered every 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg/kg/day. Method for preparing solutions for parenteral use. Preparation of the solution. Total dose (g) 0.5. Equivalent doses of sulbactam + cefoperazone, (g) 0.25 + 0.25; volume of solvent, (ml) 1.7; maximum final concentration (mg/ml) 125 + 125. Total dose (g) 1.0. Equivalent doses of sulbactam + cefoperazone, (g) 0.5 + 0.5; volume of solvent, (ml) 3.4; maximum final concentration (mg/ml) 125 + 125. Total dose (g) 2.0. Equivalent doses of sulbactam + cefoperazone, (g) 1.0 + 1.0; volume of solvent, (ml) 6.7; maximum final concentration (mg/ml) 125 + 125. Total dose (g) 3.0. Equivalent doses of sulbactam + cefoperazone, (g) 1.5 + 1.5; volume of solvent, (ml) 10.2; maximum final concentration (mg/ml) 125 + 125. Total dose (g) 4.0. Equivalent doses of sulbactam + cefoperazone, (g) 2.0 + 2.0; volume of solvent, (ml) 13.6; maximum final concentration (mg/ml) 125+ 125. Intramuscular administration. Preparation of a solution using lidocaine. To prepare a solution for intramuscular administration, you can use a 2% solution of lidocaine hydrochloride, but it cannot be used for initial dissolution, given their incompatibility. Compatibility can be achieved by a two-step solution preparation - initially the powder is dissolved in sterile water for injection and then diluted with a 2% solution of lidocaine hydrochloride. Intramuscular administration is not recommended for a single dose exceeding 2 g. The final solution will contain cefoperazone/sulbactam in a ratio of 125 mg/125 mg in 1 ml of 0.5% lidocaine solution. Intravenous administration. To prepare a solution for infusion, the contents of the bottle are diluted in an adequate volume (see table) with one of the following infusion solutions: 5% dextrose solution, 5% dextrose solution in 0.225% sodium chloride solution, 5% dextrose solution in 0.9% sodium chloride solution , 0.9% sodium chloride solution or sterile water for injection, and then diluted to 20 ml with the same solvent used for the initial dilution. Preparation of a solution using Ringer's lactate. Since Ringer's lactate is not suitable for initial dilution, the solution is prepared in two stages: first, use sterile water for injection (see table above), and then the resulting solution is diluted with Ringer's lactate solution to a sulbactam concentration of 5 mg/ml (2 ml of the initial solution is diluted in 50 ml of lactated Ringer's solution or 4 ml in 100 ml of lactated Ringer's solution). The infusion is carried out over 15-60 minutes. For intravenous injection, the contents of each vial should be dissolved in an adequate volume (see table) of one of the solvents described in the preparation of solution for infusion (see above) and administered over a minimum of 3 minutes.
