Cefoperazone + Sulbactam
Cefoperazone + Sulbactam: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Cefoperazone + Sulbactam
ATX code: J01DD62
Active ingredient: cefoperazone (cefoperazone) + sulbactam (sulbactam)
Manufacturer: Harbin Pharmaceutical Group Co. (China), ATM Sanita Pharma (Uzbekistan), Krasfarma, JSC (Russia)
Description and photo updated: 2018-23-11
Cefoperazone + Sulbactam is a combined broad-spectrum antibacterial drug.
Release form and composition
Dosage form of the drug Cefoperazone + Sulbactam - powder for solution for injection: crystalline, white (in a cardboard box 1 bottle).
Active substances in 1 bottle:
- cefoperazone sodium - 0.5 g or 1 g;
- sodium sulbactam - 0.5 g or 1 g.
Pharmacological properties
Pharmacodynamics
The antibacterial component of the drug, cefoperazone, is a third-generation cephalosporin. It acts bactericidal (by inhibiting the synthesis of the bacterial wall).
Sulbactam has no real antibacterial activity, the exception is activity against Acinetobacter and Neisseriaceae. However, sulbactam is a beta-lactamase inhibitor (these are enzymes that are produced by microorganisms that are resistant to beta-lactam antibiotics).
Sulbactam helps to prevent the destruction of penicillins and cephalosporins by resistant microorganisms. In addition, there is a pronounced synergism with cephalosporins and penicillins. Sulbactam also binds to some penicillin-binding proteins, therefore sensitive microorganisms are more susceptible to the action of sulbactam / cefoperazone than to the action of cefoperazone alone.
The combination of sulbactam with cefoperazone is active against the following microorganisms: Citrobacter diversus, Citrobacter freundii, Haemophilus influenzae, Bacteroides spp., Enterobacter aerogenes, Acinetobacter calcoaceticus, Escherichia coli, Enterobacter cloacae, Klebsiella morganella pneumeonia
In vitro, Cefoperazone + Sulbactam is active against a wide range of clinically significant microorganisms:
- gram-positive microorganisms: Staphylococcus aureus (including strains producing / not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae (mainly Diplococcus pneumoniae), Streptococcus pyogenes, and Streptococcus agalactia groups) most other types of beta-hemolytic streptococci, many species of Streptococcus faecalis;
- gram-negative microorganisms: Escherichia coli, Enterobacter, Citrobacter and Klebsiella spp., Haemophilus influenzae, Proteus vulgaris, Proteus mirabilis, Morganella morganii (mainly Proteus morganii), Providencia rettgeri (mainly Proteus rettgeri), Providencia spp. including S. marcescens), Shigella and Salmonella species, Pseudomonas aeruginosa, Yersinia enterocolitica, Acinetobacter calcoaceticus, Neisseria meningitidis, Neisseria gonorrhoeae, Bordetella pertussis, some Pseudomonas species;
- anaerobic microorganisms: gram-negative bacilli (including Bacteroides fragilis, other Bacteroides species and Fusobacterium species), gram-positive bacilli (including Clostridium, Eubacterium and Lactobacillus species), gram-positive / gram-negative cocci, Peptostreptococcus and Veillonella).
Pharmacokinetics
After intravenous administration of 1 g of cefoperazone, C max (maximum concentration of the substance) is 0.114 mg / ml, the time to reach it is 30 minutes. After intravenous administration of 0.5 or 1 g of sulbactam, C max is 0.021–0.04 mg / ml and 0.048–0.088 mg / ml, the time to reach it is 15 minutes.
Plasma protein binding: cefoperazone - from 82 to 93%, sulbactam - 38%.
The average values of C max of sulbactam and cefoperazone after the introduction of 2 g of the drug Cefoperazone + Sulbactam intravenously for 5 minutes are 0.130 2 and 0.236 8 mg / ml, respectively. Of the two active substances, sulbactam has a larger volume of distribution, equal to 18-27.6 liters (the volume of distribution of cefoperazone is 10.2-11.3 liters).
Both active substances are subject to intensive distribution in body fluids and tissues, including the gallbladder, bile, skin, fallopian tubes, appendix, uterus, ovaries, etc.
When the solution for injection Cefoperazone + Sulbactam is administered, approximately 84% of the dose of sulbactam and 25% of the dose of cefoperazone are excreted by the kidneys. Most of the dose of cefoperazone is excreted in the bile. After administration of the drug, the average T 1/2 (half-life) of sulbactam is 1 hour, cefoperazone - 1.7 hours. Plasma concentrations are proportional to the administered dose.
In pediatric patients, the average T 1/2 of sulbactam is in the range of 0.91–1.42 hours, cefoperazone –1.44–1.88 hours.
After repeated administration of any significant changes in the pharmacokinetic processes of the components of the drug Cefoperazone + Sulbactam was not detected, cumulation when applied every 8-12 hours is not observed.
Indications for use
- upper / lower urinary tract infections;
- upper / lower respiratory tract infections, including bacterial sinusitis;
- abdominal infections including cholecystitis, peritonitis, cholangitis;
- a pelvic infection, including endometritis;
- infections of the skin, soft tissues, joints and bones;
- meningitis;
- septicemia;
- gonorrhea.
Contraindications
Absolute:
- lactation period;
- individual intolerance to the components of the drug.
Relative (Cefoperazone + Sulbactam is prescribed under medical supervision):
- neonatal period;
- pregnancy.
Instructions for use Cefoperazone + Sulbactam: method and dosage
The method of administration of the drug Cefoperazone + Sulbactam: intramuscularly and intravenously.
Before starting therapy, a skin test for tolerance should be performed.
The usual adult daily dose is 2–4 g, divided into 2 equal portions and given every 12 hours. When treating severe / resistant infections, an increase in the daily dose up to 8 g (maximum) is permissible.
In severe obstructive jaundice and severe liver disease, or in cases where both pathologies are accompanied by impaired renal function, the dose of Cefoperazone + Sulbactam is adjusted.
In case of impaired liver function and concomitant impairment of renal function, control of the plasma concentration of cefoperazone and, if necessary, dose adjustment is required. If concentration monitoring is not possible, the maximum dose of cefoperazone should be 2 g per day.
In cases of using the drug with a significant decrease in renal function (creatinine clearance <30 ml / min), to compensate for the reduced clearance of sulbactam, the daily dose of the drug is adjusted. With creatinine clearance of 15-30 ml / min and <15 ml / min, the maximum single dose of sulbactam should be 1 and 0.5 g, the daily dose should be 2 and 1 g, respectively. In severe infections, additional administration of cefoperazone is possible.
When using hemodialysis, the dose of the drug Cefoperazone + Sulbactam is subject to correction (associated with a change in the pharmacokinetic profile of sulbactam and a decrease in T 1/2 of cefoperazone).
The average dose for children is 0.04–0.08 g / kg per day. The daily dose is divided evenly and administered 2–4 times a day at regular intervals. For severe / refractory infections, the dose may be increased to 0.16 g / kg per day.
Cefoperazone + Sulbactam is administered every 12 hours for newborns of the first week of life. The maximum daily dose is 0.08 g / kg.
Before the drop infusion, the contents of each vial must be dissolved in an appropriate amount of 5% dextrose in water, 0.9% sodium chloride solution or sterile water for injection. Immediately before administration, the volume is adjusted to 20 ml with a similar solution. The drug is administered for 15-60 minutes.
Cefoperazone + Sulbactam is compatible with water for injection, 5% dextrose solution in 0.225% saline solution and 5% dextrose in normal saline solution at concentrations of 0.01–0.125 g / ml of each of the active substances.
Ringer's lactate solution can be used for dilution by intravenous infusion; it cannot be used for primary dilution.
For intravenous injection, the drug is diluted in the same way. Administration time is at least 3 minutes.
When used intramuscularly, lidocaine chloride is an acceptable dilution solution; it cannot be used for primary dilution.
Side effects
- digestive system: diarrhea, vomiting, nausea, pseudomembranous colitis;
- cardiovascular system: vasculitis, arterial hypotension;
- hematopoietic system: leukopenia, a slight decrease in the number of neutrophils; with prolonged use - reversible neutropenia; in some cases, a positive direct Coombs' test, decreased hemoglobin / hematocrit, eosinophilia, thrombocytopenia, and hypoprothrombinemia;
- nervous system: a decrease in the reserve of albumin concentration (due to cefoperazone); in the treatment of newborns with jaundice - an increase in the likelihood of developing bilirubin encephalopathy;
- urinary system: hematuria;
- skin reactions: maculopapular rash, itching, urticaria, Stevens-Johnson syndrome (the likelihood of violations is higher in patients with a history of allergic reactions, in particular to penicillins);
- local reactions: with intramuscular injection (rarely) - pain at the injection site; with infusion - phlebitis at the infusion site when the solution is administered through an intravenous catheter;
- laboratory parameters: inconsistent increase in the indicators of functional liver tests of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin levels;
- others: fever, headache, muscle twitching, pain at the injection site, anaphylactic reactions (including shock).
Overdose
Main symptoms: increased side effects. It should be borne in mind that at high concentrations of beta-lactam antibiotics in the cerebrospinal fluid, neurological reactions, in particular seizures, may develop.
Cefoperazone and sulbactam are secreted from the circulation system by hemodialysis, therefore this procedure can lead to increased elimination of the drug from the body in case of overdose in patients with impaired renal function.
Therapy: symptomatic. There is no specific antidote.
special instructions
Due to the increased risk of bleeding, Cefoperazone + Sulbactam should be used with caution in weakened patients with malabsorption, as well as with alcohol consumption.
In cases of superinfection, appropriate treatment is required.
With the development of allergic reactions, therapy should be discontinued immediately and appropriate treatment should be prescribed. Severe anaphylactic reactions require immediate emergency therapy (eg, epinephrine). If indicated, oxygen therapy, intravenous corticosteroids can be used, and airway patency, including intubation, must be ensured.
In some patients, the use of cefoperazone leads to the development of vitamin K deficiency. The risk group includes patients with limited nutrition, malabsorption (for example, with gallbladder fibrosis), as well as patients who have been on parenteral (intravenous) nutrition for a long time. These patients require prothrombin time control. Similar monitoring is necessary for patients using anticoagulants. In such cases, additional prescription of exogenous vitamin K is possible.
As with the use of other antibiotics, prolonged treatment with Cefoperazone + Sulbactam can lead to an increased growth of resistant microflora. In this regard, the patient's condition must be carefully monitored. It is necessary to take into account the likelihood of periodic manifestations of violations of the activity of the kidneys, liver and hematopoietic system. In particular, this warning applies to the treatment of newborns (including premature babies).
Application during pregnancy and lactation
- pregnancy: the use of the drug Cefoperazone + Sulbactam is possible only after assessing the ratio of the expected benefit with the possible risk (no controlled studies have been conducted);
- lactation period: therapy is contraindicated, since Cefoperazone + Sulbactam is excreted in breast milk in a small amount.
Pediatric use
Before starting use in premature infants or newborns, the ratio of the expected benefit to the possible risk should be assessed. Cefoperazone + Sulbactam has been used effectively in infants, but no controlled studies have been conducted.
Drug interactions
According to the instructions, Cefoperazone + Sulbactam is physically incompatible with the following drugs: filgrastim, amifostine, labetalol, perphenazine, nicardipine, meperidine, ondansetron, pethidine, promethazine, sargramostim, vinorelbine.
During therapy, as well as for another 5 days after its end, it is not recommended to drink alcohol. This is due to the likelihood of developing the following reactions: facial flushing, headache, sweating, tachycardia. You should also avoid the use of artificial nutrition containing ethanol (oral or parenteral solutions).
Solutions of Cefoperazone + Sulbactam and aminoglycosides should not be mixed directly, due to their physical incompatibility. If combination therapy is required, they must be applied sequentially using a separate secondary intravenous (IV) tubing system. The primary IV tubing system should be thoroughly flushed with an appropriate solution between infusions. It is advisable that the intervals between the injections of the Cefoperazone + Sulbactam solution for injections and the aminoglycoside solutions during the day should be as long as possible.
When using Fehling's or Benedict's solution, there may be a false-positive reaction to glucose in the urine.
Analogs
Analogs of Cefoperazone + Sulbactam: Sulperacef, Sulcef, Sulmover, Cefbactam, Sulperazon, Tsebanex, Sulzontsef, Bakperazon, Sulmagraf, Cefpar SV, Cefoperazone and Sulbactam Jodas, Cefoperazon and Sulbaktam.
Terms and conditions of storage
Store in a place protected from light at a temperature of 15-25 ° C. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Cefoperazone + Sulbactam
According to a few reviews, Cefoperazone + Sulbactam is an effective broad-spectrum antibacterial drug. The development of side effects is rarely reported.
Price for Cefoperazone + Sulbactam in pharmacies
The price of Cefoperazone + Sulbactam is unknown, since the drug is not available in pharmacies. The approximate cost of analogs (for 1 bottle containing 1 g + 1 g of active substances): Bakperazon - 133 rubles, Sulzontsef - 130–150 rubles, Sulperazon - 357–511 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!