Universal reference book for medicines
Product name: PACTTOSEF (PACTOCEF)

Active substance: cefoperazone, sulbactam

Type: Cephalosporin III generation with a beta-lactamase inhibitor

Manufacturer: PROTECH BIOSYSTEMS (India)
Composition, form of production and packaging
Powder for the preparation of solution for iv and in / m introduction of
white or almost white color.

1 f.

cefoperazone (in the form of sodium salt) 1 g

sulbactam (in the form of the sodium salt) 1 g

2 g - glass bottles (1) - cardboard packs.

Powder for the preparation of solution for iv and in / m introduction of white or almost white color.

1 f.

cefoperazone (in the form of the sodium salt) 250 mg

sulbactam (in the form of the sodium salt) 250 mg

500 mg - glass bottles (1) - packs of cardboard.

Powder for the preparation of solution for iv and in / m introduction of white or almost white color.

1 f.

cefoperazone (in the form of the sodium salt) 500 mg

sulbactam (in the form of the sodium salt) 500 mg

1 g - glass bottles (1) - packs of cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2011.

PHARMACHOLOGIC EFFECT

Pacoceph - a combined antibacterial preparation of a wide spectrum of action.

Cefoperazone is a semisynthetic antibiotic of the third generation of the cephalosporin series intended for parenteral use only.
It is bactericidal, has a wide spectrum of action; It is highly active against aerobic and anaerobic Gram-positive and Gram-negative microorganisms. The mechanism of action is the inhibition of the biosynthesis of the mucopeptide of the cell wall.
Sulbactam is a derivative of the main nucleus of penicillin.
It is an irreversible inhibitor of beta-lactamases, which are released by microorganisms resistant to beta-lactam antibiotics; prevents the destruction of penicillins and cephalosporins under the action of beta-lactamases of resistant microorganisms; binding to penicillin-binding proteins, shows a synergism with simultaneous application with penicillins and cephalosporins. Sulbactam does not have clinically significant antibacterial activity (except for Neisseriaceae and Acinetobacter spp.). 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 cefoperazone + [sulbactam] is active against all microorganisms sensitive to cefoperazone and acts synergistically (reduces the minimum inhibitory concentration (MIC) of the combination up to 4 times compared to cefoperazone) against microorganisms: Haemophilus influenzae, Bacteroides spp., Staphylococcus spp. , Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.
Cefoperazone + [sulbactam] is invitro active against a wide range of clinically relevant microorganisms:

Gram-positive microorganisms

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta beta-hemolytic streptococcus, Streptococcus agalactiae (group B beta-hemolytic streptococcus), most other strains of beta-hemolytic streptococci, many strains of Enterococcus faecalis .

Gram-negative microorganisms

Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia spp., Serratia spp.
(including Serratia marcescens), Salmonella spp. and Shigella spp., Pseudomonas aeruginosa and several other Pseudomonas spp., Acinetobactercal coaceticus, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica.
Anaerobic microorganisms

Gram-negative bacilli (including Bacteroides fragilis, other Bacteroides spp., And Fusobacterium spp.).

Gram-positive and Gram-negative cocci (Including Peptococcus spp., Peplostreptococcus spp. And Veillonella spp).

Gram-positive sticks (including Clostridium spp., Eubacterium spp., And Lactobacillus spp.).

PHARMACOKINETICS

Suction and distribution

C max in the serum of cefoperazone and sulbactam after intravenous administration of cefoperazone + [sulbactam] at a dose of 2 g (1 g of cefoperazone, 1 g of sulbactam) is achieved within 5 minutes and averages 237 μg / ml for cefoperazone and 130 μg / ml for the sulbactam.
This reflects a higher V d of sulbactam (V d = 18-28 L) compared with that of cefoperazone (V d = 10-11 L).
Cefoperazone and sulbactam are distributed well in various tissues and body fluids, including ascitic fluid, spinal fluid (in patients with inflammation of the meninges), urine, saliva, tonsils, skin, fallopian tubes, ovaries, uterus, lungs, bones, bile, gallbladder , appendix.
The drug penetrates the placental barrier.
Cefoperazone by 70-90%, sulbactam by 38% reversibly bind to plasma proteins.

Metabolism and excretion

T 1/2 of sulbactam averages about 1 hour, T 1/2 of cefoperazone - 1.7 hours.
Serum concentration is proportional to the administered dose.
Approximately 84% of the dose of sulbactam and 25% of the dose of cefoperazone are excreted by the kidneys.
The rest of cefoperazone is excreted mainly with bile.
With repeated application of significant changes in the pharmacokinetic parameters of both components of the drug was not noted.
When the drug was administered every 8-12 h, cumulation was not observed.
Pharmacokinetics in special clinical cases.

When a violation of liver function

Cefoperazone is actively excreted with bile.
T 1/2 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 T 1/2increases only 2-4 times.
In case of impaired renal function

Patients with varying degrees of renal dysfunction who received cefoperazone + [sulbactam] showed a high correlation between total clearance of sulbactam from the body and estimated clearance of creatinine.
In patients with terminal renal failure, a significant elongation of T 1/2 of sulbactam was found (an average of 6.9 and 9.7 hours in various studies). Hemodialysis caused significant changes in T 1/2 total clearance and V d of sulbactam.
In the elderly

The pharmacokinetics of cefoperazone + [sulbactam] has been studied in elderly people with renal insufficiency and impaired liver function.
In comparison with healthy volunteers, an increase in the duration of T 1/2 , a decrease in clearance and an increase in V d of both sulbactam and cefoperazone were revealed. The pharmacokinetics of sulbactam correlated with the degree of renal dysfunction, and the pharmacokinetics of cefoperazone - with a degree of impaired hepatic function.
Children

In studies in children, there were no significant changes in the pharmacokinetic parameters of the components of cefoperazone + [sulbactam] compared with those in adults.
The mean T 1/2 of sulbactam in children was 0.9-1.4 h, of cefoperazone 1.4-1.8 h.
INDICATIONS

Infectious-inflammatory diseases caused by microorganisms sensitive to cefoperazone / sulbactam:

- infections of the upper and lower respiratory tract (pharyngitis, tonsillitis, bronchitis, pneumonia, bronchopneumonia, empyema of the pleura, lung abscess);

- infection of the ENT organs (sinusitis, otitis media);

- infections of the upper and lower urinary tract (pyelonephritis, cystitis);

- intra-abdominal infections (peritonitis, cholecystitis, cholangitis, liver abscesses);

- sepsis;

- meningitis;

- skin and soft tissue infections (furunculosis, abscess, pyoderma, lymphadenitis, lymphangitis);

- infections of bones and joints (osteomyelitis);

- Inflammatory diseases of the pelvic organs (endometritis, gonorrhea);

- prevention of infectious complications after abdominal, gynecological and orthopedic operations, in cardiovascular surgery.

DOSING MODE

In / in (struyno and drip) and in / m.

The dose of cefoperazone + [sulbactam] depends on the severity of the disease, type of infection, body condition, age, body weight and kidney function in the patient.

Application in adults

In adults, cefoperazone + [sulbactam] is recommended for use in the following daily doses:

Ratio of cefoperazone + [sulbactam] dose (g) Sulbactam dose (g) cefoperazone 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. For severe and refractory infections, the daily dose of cefoperazone + [sulbactam] can be increased to 8 g with a 1: 1 ratio of the major components (ie 4 g of cefoperazone).
If you need more than 8 g (with a 1: 1 ratio of the main components), an increase in the dose is achieved by the 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 creatinine clearance of 15-30 ml / min, the maximum dose of sulbactam is 1 g every 12 hours (maximum daily dose of sulbactam is 2 g), and inpatients with creatinine clearance less than 15 ml / min, the maximum dose of sulbactam is 500 mg every 12 hours the 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.

T 1/2 of cefoperazone from the blood plasma is slightly reduced 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.

Use in children

In children, cefoperazone + [sulbactam] is recommended for use in the following daily doses:

The ratio of Cefoperazone + [sulbactam] dose (mg / kg / day) Sulbactam dose (mg / kg / day) Cefoperazone dose (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.

In severe and refractory infections, the daily dose can be increased to 160 mg / kg / day with a 1: 1 ratio of the major components.
The daily dose is divided into 2-4 equal parts. If you need more than 80 mg / kg / day, calculated from the activity of cefoperazone, an increase in dose is achieved through the additional administration of cefoperazone.
Neonatal application

In newborns during the first week of life, the drug should be injected every 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg / kg / day.
Method of preparing solutions for parenteral use
Breeding:

Total dose (g) Equivalent dose of cefoperazone + [sulbactam] Volume of solvent, ml Maximum final concentration, mg / ml

0.5 0.25 + 0.25 1.7 125 + 125

1.0 0.5 + 0.5 3.4 125 + 125

2.0 1.0 6.7 125 + 125

Intramuscular injection:

Sterile water for injection is used for dissolution.
If the drug is administered with a concentration of cefoperazone exceeding 250 mg / ml, it is recommended to prepare the solution using a lidocaine solution. The dilution is carried out in 2 stages - 0.65 ml of sterile water for injection is added to a vial containing 0.5 g of the drug (in a vial containing 1.3 grams of 1 g, in a vial containing 2 grams - 2.6 ml), shaken until completely dissolved, and then added 0.2 ml 2% lidocaine solution (in a vial containing 1 g of the drug - 0.4 ml, into a vial containing 2 g - 0.8 ml). The final solution will contain in 1 ml 0.5% lidocaine solution about 250 mg of cefoperazone and about 250 mg of sulbactam.
IV introduction:

For intravenous administration, the contents of the vial are dissolved in an adequate volume of 5% dextrose solution, 0.9% sodium chloride solution, 5% dextrose solution in 0.225% sodium chloride solution, 5% dextrose solution in 0.9% sodium chloride solution or sterile water for injection and inject within 3 minutes.

For IV infusion introduction dissolve, as mentioned above, then dilute to 20-100 ml with the same solvent and injected for 15-60 minutes.
Preparation of the solution using Ringer's solution of lactate. Because Ringer's lactate solution is not suitable for initial dilution, the solution is prepared in two steps: first, sterile water for injection is used, and then the resulting solution is diluted with Ringer's lactate solution to a concentration of 5 mg / ml of sulbactam. Infusion is carried out for 15-60 minutes.
SIDE EFFECT

From the cardiovascular system: lowering blood pressure.

From the digestive system: diarrhea, nausea, vomiting, pseudomembranous colitis.

Allergic reactions: maculopapular rash, hives, itching, Stevens-Johnson syndrome, anaphylactic shock.

From the hemopoietic system: bleeding (vitamin K deficiency), a decrease in the number of neutrophils.
With long-term treatment, reversible neutropenia, a decrease in hemoglobin and hematocrit, transient eosinophilia, thrombocytopenia, leukopenia, hypoprothrombinemia develops.
Local reactions: sometimes after intramuscular injection, there is transient pain and burning at the injection site.
With iv administration of the drug, phlebitis may develop at the site of administration.
Laboratory indices: hypercreatininaemia, transient accumulation of activity of "hepatic" transaminases, alkaline phosphatase, hyperbilirubinemia, hematuria, false-positive Coombs test.
When using a solution of Benedict or Felling, a false positive reaction to glucose in the urine can be observed.
Other: headache, fever, chills, vasculitis.

CONTRAINDICATIONS

- hypersensitivity to sulbactam, cefoperazone, penicillins and other beta-lactam antibiotics.

With caution severe violations of kidney and liver function, colitis (including in history), children's age of up to 3 months.

PREGNANCY AND LACTATION

The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus.
If you need to use the drug during lactation, you should decide whether to stop breastfeeding.
SPECIAL INSTRUCTIONS

Considering the wide spectrum of activity, it is possible to conduct adequate monotherapy.
Patients who received β-lactam antibiotics, such as cephalosporins, described cases of severe reactions of hypersensitivity (anaphylactic).
Risk of hypersensitivity reactions, incl.
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 urgent epinephrine.
In / in injected SCS and provide airway patency, including intubation.
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 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.
When using a solution of Benedict or Feling, a false-positive reaction to glucose in the urine, false-positive Coombs test can be observed.
With the simultaneous use of aminoglycosides, kidney function should be monitored.
With prolonged use of the drug, a violation of normal intestinal microflora is possible, which can lead to the growth of Clostridium difficile and cause the development of pseudomembranous colitis.
In this case, it is necessary to cancel the drug, the purpose of a specific treatment. The use of drugs that inhibit the intestinal peristalsis is contraindicated.
In the treatment of cefoperazonom in rare cases, vitamin K deficiency developed. Patients receiving malnutrition, suffering from malabsorption (for example, in cystic fibrosis) and those who are long-term on intravenous artificial feeding may be classified as a risk group.
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.
With prolonged therapy, it is recommended to periodically monitor the performance of internal organs, including the kidneys, liver and hematopoiesis system, especially in newborns, especially premature babies, and young children.
Impact on the ability to drive vehicles and manage mechanisms

During treatment, a combination of cefoperazone + [sulbactam] should refrain from driving vehicles and performing work that requires increased attention and speed of psychomotor reactions.

OVERDOSE

Symptoms: neurological disorders, including convulsions.

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

DRUG INTERACTION

Solutions cefoperazona + [sulbactam] and aminoglycosides should not be mixed, given the pharmaceutical incompatibility between them.
If combined therapy is used, the two drugs are administered by successive infusions using separate secondary catheters, and the primary catheter is washed between doses of the drugs. Intervals between administration during the day should be as large as possible. In the process of treatment, it is necessary to monitor kidney function. When ethanol is used during treatment with cefoperazone and for up to 5 days after its administration, development of disulfiram-like effects, characterized by "hot flashes", sweating, headache and tachycardia, is possible.
In patients who require artificial feeding (inside or parenteral), the use of solutions containing ethanol should be avoided.

The drug is incompatible with Ringer's lactate solution, a 2% solution of lidocaine (the initial use of water giving injections leads to the formation of a compatible mixture).
Compatible with water for injection, 5% dextrose solution, 0.9% sodium chloride solution, 5% dextrose solution in 0.225% sodium chloride solution, 5% dextrose solution in 0.9% sodium chloride solution.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

Store in a 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 expiration date.
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