Cefoperazone and Sulbaktam Spencer - instructions for use, dose, side effects, contraindications

Composition:Active substances: cefoperazone sodium salt (equivalent to cefoperazone) - 1000 mg; sulbactam sodium salt (equivalent to sulbactam) - 1000 mg.

Description:

From white to white with a yellowish hue of color, crystalline powder.

Pharmacotherapeutic group:Antibiotic - cephalosporin + beta-lactamase inhibitor

ATX: & nbsp

J.01.D.D.62 Cefoperazone in combination with other drugs

Pharmacodynamics:

The antibacterial component of cefoperazone / sulbactam is cefoperazone - Third generation cephalosporin, which acts on sensitive microorganisms during their active propagation by inhibiting the biosynthesis of the mucopeptide of the cell wall. Sulbactam does not have clinically significant antibacterial activity (except for Neisseriaceae and Acinetobacter). However, it was noted that it is an irreversible inhibitor of most major beta-lactamases, which are produced by microorganisms resistant to beta-lactam antibiotics.

The ability of sulbactam to prevent the destruction of penicillins and cephalosporins by resistant microorganisms was confirmed in studies using resistant strains for which sulbactam possessed a pronounced synergism with pencillins and cephalosporins.In addition, sulbactam interacts with some penicillin-binding proteins, so cefoperazone / sulbactam often has a more pronounced effect on sensitive strains than one cefoperazone.

The combination of sulbactam and cefoperazone is active against all microorganisms sensitive to cefoperazone. In addition, it has a synergistic effect on various microorganisms, primarily: Haemophilus influenzae, Bacteroides species, Staphylococcus species, Acinetobacter calcoaceticus, Enterobacler aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacler cloacae. Citrobacter diversus.

Cefoperazone / sulbactam is active in vitro for a wide range of clinically relevant microorganisms.

- Gram-positive microorganisms

Staphylococcus aureus (producing and not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic group streptococcus A), Streptococcus agalactiae (beta-hemolytic streptococcus group B), most other strains of beta-hemolytic streptococci, many strains Streptococcus faecalis (enterococci).

- Gram negative microorganisms

Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis. Proteus vulgaris, Morganella morganii, Providencia rettgeri, Provide ncia spp., Serratia spp. (including Serratia marcescens), Salmonella and Shigella spp., Pseudomonas aeruginosa and some others Pseudomonas spp., Acinetobacter calcoaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enlerocolitica.

- Anaerobic microorganisms

Gram-negative sticks (including Bacteroides fragiiis, others Bacteraides species and Fusobacterium spp).

Gram-positive and Grai negative cocci (including Peptococcus, Peptostreptococcus and Veillonella spp.). Gram-positive sticks (including Clostridium spp., Eubacterium spp. and Lactobacillus spp.).

The following sensitivity levels were established for cefoperazone / sulbactam. The minimum inhibitory concentration (MPC) in μg / ml expressed in the concentration of cefoperazone for sensitive microorganisms is less than or equal to 16, for organisms with intermediate sensitivity is in the range of 17-63, and for resistant ones - more than 64. Sensitivity zones when determined by the disk diffusion method are : for sensitive microorganisms more than 21 mm; with an intermediate sensitivity of 16 to 20 mm, and for resistant - more than 15 mm.

Pharmacokinetics:

The maximum concentrations of sulbactam and cefoperazone after intravenous administration of 2 g of cefoperazone / sulbactam (1 g of sulbactam, 1 g of cefoperazone) for 5 minutes averaged 130.2 and 236.8 μg / ml, respectively. This reflects a higher volume of distribution of sulbactam (Vd = 18.0-27.6 l) compared with that of cefoperazone (Vd = 10.2-11.3 L).

After intramuscular administration, 1.5 g of cefoperazone / (0.5 g of sulbactam, 1 g of cefoperazone) the maximum concentrations of sulbactam and cefoperazone in the serum were observed from 15 minutes to 2 hours after administration.The maximum serum concentrations were 19.0 and 64.2 μg / ml of sulbactam and cefoperazone, respectively.

Both sulbactam and cefoperazone well distributed into various tissues and fluids, including bile, gall bladder, skin, appendix, fallopian tubes, ovaries, uterus, etc. Sulbactam and cefoperazone penetrate through the placental barrier.

There is no data on the presence of any pharmacokinetic interaction between sulbactam and cefoperazone with the introduction of cefoperazone / sulbactam.

With repeated use of significant changes in the pharmacokinetics of both components of sulbactam / cefoperazone was not noted. With the introduction of the drug every 8-12 hours cumulation was not observed.

Approximately 84% of the dose of sulbactam and 25% of the dose of cefoperazone, administered as a combination - cefoperazone / sulbactam, is excreted by the kidneys. Most of the remaining dose of cefoperazone is excreted with bile. Cefoperazone Do not displace bilirubin from the connection with plasma proteins. The half-life of sulbactam averages about 1 hour, cefoperazone - 1.7 hours. Serum concentration is proportional to the administered dose.

When a violation of liver function

Cefoperazone is actively excreted with bile.The half-life of cefoperazone usually lengthens, and the excretion of the drug by the kidneys increases in patients with liver disease and / or biliary tract obstruction. Even with a serious violation of liver function in bile, the therapeutic concentration of cefoperazone is reached, and the elimination half-life increases only 2-4 times.

In case of impaired renal function

In patients with varying degrees of renal dysfunction, receiving cefoperazone / sulbactam, a high correlation was found between the total clearance of sulbactam from the body and the estimated clearance of creatinine. In patients with terminal renal failure, a significant elongation of the half-life of sulbactam (an average of 6.9 and 9.7 hours in various studies) was found. Hemodialysis caused significant changes in the half-life, total clearance and volume of distribution of sulbactam.

Application in the elderly

The pharmacokinetics of cefoperazone / sulbactam has been studied in elderly people with renal insufficiency and impaired liver function. Compared with healthy volunteers, an increase in the half-life, a decrease in clearance, and an increase in the distribution of both sulbactam and cefoperazone have been found.The pharmacokinetics of sulbactam correlated with the degree of impaired renal function, and the pharmacokinetics of cefoperazone - with a degree of impaired hepatic function.

Use in children

In studies in children, no significant changes in the pharmacokinetics of the components of cefoperazone / sulbactam were found in comparison with those in adults. The mean half-life of sulbactam in children was 0.91 to 1.42 h, of cefoperazone from 1.44 to 1.88 h.

Indications:

Infectious-inflammatory diseases caused by sensitive microorganisms:

- infections of the upper and lower respiratory tract;

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

- peritonitis, cholecystitis, cholangitis and other intra-abdominal infections;

- sepsis, meningitis;

- infections of the skin and soft tissues;

- infection of bones and joints;

- inflammatory diseases of the pelvic organs, endometritis, gonorrhea and other infections of the urinary tract;

- prevention of postoperative complications.

Contraindications:Hypersensitivity to penicillin, sulbactam, cefoperazone or other cephalosporins and beta-lactams.

Carefully:Severe violations of kidney and liver function, children under 3 months.

Pregnancy and lactation:In pregnancy, the drug is used only if the expected benefit to the mother exceeds the potential risk to the fetus. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenous and intramuscular.

Application in adults

In adults, cefoperazone / destubactam is recommended for use in the following daily doses:

Ratio Cefoperazone and Sulbactam Sulbactam Cefoperazone

dose (g) dose (g)

1:1 2,0-4,0 1,0-2,0 1,0-2,0

The daily dose should be divided into equal parts and administered every 12 hours. In severe or refractory infections, the daily dose of cefoperazone / sulbactam can be increased to 8 g at ratio of the main components 1: 1 (i.e., 4 g of cefoperazone).

Patients receiving cefoperazone / sulbactam 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.

Application for renal dysfunction

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 creatinine clearance less than 15 ml / min, the maximum dose of sulbactam is 500 mg every 12 hours (maximum daily dose of sulbactam 1 g). In severe infections, additional administration of cefoperazone may be required.

The pharmacokinetics of sulbactam significantly changes during hemodialysis. The half-life of cefoperazone from the blood serum decreases slightly during hemodialysis. Therefore, the administration of the drug should be planned after dialysis. Application for violations of liver function

If regular monitoring of serum concentration of cefoperazone is not performed, the maximum daily dose should not exceed 2 g (see section "Special instructions").

Use in children

In children, sulbactam / cefoperazone is recommended for use in the following daily doses: Cefeperazone / Sulbactam ratio Sulbactam Cefoperazone dose

(mg / kg / day) dose (mg / kg / day) (mg / kg / day)

1:1 40-80 20-40 20-40

The dose should be divided into equal parts and administered every 6-12 hours.

For serious or refractory infections, these dosages can be increased to 160 mg / kg / day for a 1: 1 ratio of the major components. The daily dose dividing g into 2-4 equal parts.

Neonatal application

In newborns be administered every 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg / kg / day during the first week of life of the drug.

Method of preparing solutions for parenteral use

Preparation of the solution

Total dose (g) Equivalent doses	Scope	Max. ultimate
cefoperazone + sulbactam	solvent	conc. (mg / ml)
2,0 1,0+1,0	6,7	125 + 125

- Intramuscular injection

Preparation of a solution using lidocaine. For preparation of a solution for intramuscular injection may be used 2% lidocaine hydrochloride solution, but it can not be used for initial dissolution, given their incompatibility. Compatibility can be achieved by two-step preparation of the solution - the original powder is dissolved in sterile water for injection and then diluted with 2% lidocaine hydrochloride. The total volume of the solvent is 6.7 ml. The final solution will contain cefoperazone / sulbactam in a ratio of 125 mg / 125 mg in 1 ml of a 0.5% lidocaine solution,

- Intravenous administration

To prepare a solution for intravenous infusion diluted with 2 g (1 g + 1 g) and sulbactam Cefoperazone in the initial volume of 6.7 ml of one of the following infusion solutions: 5% dextrose in water, 5% dextrose in 0.225% solution of sodium chloride,5% dextrose solution in saline, 0.9% sodium chloride solution or sterile water for injections, and then diluted to 20 ml with the same solvent.

Preparation of the solution using Ringer's lactate. Since Ringer's lactate is not suitable for initial dilution, the solution is prepared in two steps: first use water Д1я (see table), and then the resulting solution is diluted with a solution of Ringer's lactate to a concentration of 5 mg / ml of sulbactam (2 ml of the initial solution is diluted in 50 ml of Ringer's lactate solution or 4 ml in 100 ml of Ringer's lactate solution). Infusion is carried out for 15-60 minutes.

For intravenous injection the contents of each vial should be dissolved in 6.7 ml of one from the solvents described above and administered for a minimum of 3 minutes.

Side effects:

From the cardiovascular system: lowering of blood pressure.

From the gastrointestinal tract: diarrhea, nausea, vomiting, pseudomembranous

colitis.

Allergic reactions: hypersensitivity, manifested in the form of maculopapular rash and hives, as well as itching, Stevens-Johnson syndrome, anaphylactic shock.

On the part of the hematopoiesis system: decrease in the number of neutrophils. With long-term treatment, reversible neutropenia, a decrease in the level of hemoglobin and hematocrit can develop. There is transient eosinophilia, thrombocytopenia, leukopenia, hypoprothrombinemia.

Laboratory indicators: transient increase in "liver" transaminases, alkaline phosphate and bilirubin in the blood serum, hypercreatininaemia, hematuria. In some patients, a positive Coombs test was observed during treatment. When using a solution of Benedict or Felling, a false-positive reaction to glucose in the urine can be observed.

Local reactions: After intramuscular injection, transient pain and burning at the injection site are observed. With an induction using a catheter, phlebitis can develop at the site of administration.

Other: headache, fever, pain with injection, chills, vasculitis.

Overdose:

Information on the acute toxicity of sodium cefoperazone and sodium sulbactam is limited. In case of overdose, it is possible to expect the appearance of undesirable effects registered with the use of the drug.It should be borne in mind that a high concentration of beta-lactam antibiotics in cerebrospinal fluid can lead to neurologic disorders, including convulsions.

Treatment: symptomatic, hemodialysis is effective, especially in patients with impaired renal function.

Interaction:

Solutions of cefoperazone / sulbactam and aminoglycosides should not be directly mixed, given the pharmaceutical incompatibility between them. If combined therapy is provided, the two drugs are administered by successive infusions using separate secondary catheters, and the primary catheter is washed fairly well with the solution between dosing of the drugs. Intervals between administration during the day should be as large as possible.

When ethanol is used during treatment with pepoperazone and for up to 5 days after its administration, development of disulfiramoid-like effects, characterized by "hot flashes", sweating, headache and tachycardia, is possible. Patients who need artificial feeding (inside or parenteral) should avoid using solutions containing ethanol.

Special instructions:

The risk of hypersensitivity reactions, including those leading to death, is higher in patients who have a history of hypersensitivity reactions to many allergens. In case of an allergic reaction, it is necessary to cancel the drug and prescribe adequate therapy.

Serious anaphylactic reactions require the urgent administration of epinephrine. Assign oxygen, intravenously injected glucocorticosteroids and provide airway patency, including intubation.

Dose changes may be required in cases of severe obstruction of the biliary tract, severe liver disease, as well as disturbance of the function of the nights, combined with any of these conditions.

In patients with impaired liver function and concomitant renal dysfunction, monitoring the serum concentration of cefoperazone and correcting its dose should be necessary. If regular monitoring of serum concentration of cefoperazone in such cases is not carried out, then its daily dose should not exceed 2 g.

In the treatment of cefoperazonom in rare cases, a deficiency of vitamin K.The risk group can include patients receiving malnutrition, suffering from malabsorption (for example, in cystic fibrosis) and for a long time on intravenous artificial feeding. In such cases, as well as in patients receiving anticoagulants, it is necessary to monitor prothrombin time and, in the presence of indications, prescribe vitamin K.

With prolonged treatment, excessive growth of insensitive microorganisms can be observed. Patients should be carefully observed during treatment. With prolonged therapy, it is recommended to periodically monitor the performance of internal organs, including daughters, liver and hematopoiesis system. This is especially important for newborns, especially premature babies, and small children.

Form release / dosage:Powder for the preparation of a solution for intravenous and intramuscular injection of 2 g (1.0 g of cefoperazone + 1.0 g of sulbactam).

Packaging:Powder for the preparation of a solution for intravenous and intramuscular injection of 2 g (1.0 g of cefoperazone + 1.0 g of sulbactam) of the active substance into a bottle of clear, colorless glass, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum ring.For 1 bottle with the drug, along with instructions for use in a cardboard pack.

Storage conditions:Store in a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

Powder: 2 years

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001341/07

Date of registration:29.06.2013

The owner of the registration certificate:Spencer Pharma UK LimitedSpencer Pharma UK Limited United Kingdom

Manufacturer: & nbsp

Acorn India Pvt. Ltd. India

COOPER PHARMA India

Representation: & nbspSharan Pharma, LLCSharan Pharma, LLC

Information update date: & nbsp24.10.2015

Illustrated instructions

Instructions

Cefoperazone and Sulbactam Spencer (Cefoperazone & Sulbactam Spenser)