SULPERAZON

Active material: Cefoperazone, Sulbactam
When ATH: J01DD62
CCF: III generation cephalosporin with beta-lactamase inhibitor
ICD-10 codes (testimony): A39, A40, A41, A54, G00, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, J85, J86, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, M00, M86, N10, N11, N15.1, N30, N34, N41, N70, N71, N72, N73.0
When CSF: 06.02.03.01
Manufacturer: PFIZER ILACLARI Ltd. Sti. (Turkey)

Pharmaceutical form, composition and packaging

Powder for solution for I / O, and the / m white or nearly white, with a yellowish tint.

Glass Bottles (1) – packs cardboard.

Pharmacological action

III generation cephalosporins in combination with an inhibitor of β-lactamase.

Cefoperazone - a semisynthetic cephalosporin antibiotic with broad-spectrum. It acts on the sensitive microorganisms during their active reproduction by inhibiting the biosynthesis of the cell wall peptidoglycan.

Sulbactam has no clinically significant antibacterial activity (with the exception of Neisseriaceae and Acinetobacter). Studies have shown, that it is an irreversible inhibitor of most major β-lactamase, which are produced by microorganisms, resistant to beta-lactam antibiotics.

The ability of sulbactam prevent destruction of penicillins and cephalosporins resistant microorganisms has been confirmed in studies using resistant strains, for which sulbactam has a pronounced synergy with penicillins and cephalosporins. Sulbactam is also associated with some penicillin binding proteins, so the combination of cefoperazone / sulbactam often has a more pronounced effect on the sensitive strains, than one cefoperazone.

Sulperazon active against all microorganisms, sensitive to cefoperazone. Besides, It has a synergy against various microorganisms, First of all: Haemophilus influenzae, Bacteroides spp., Staphylococcus spp., Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus is wonderful, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter different.

Sulperazon active in vitro against a broad range of clinically important microorganisms. Gram-positive microorganisms: Staphylococcus aureus (producing and not producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic streptococcus group A), Streptococcus agalactiae (beta-hemolytic streptococcus group B), Most other strains of beta-hemolytic streptococci, Many strains of Streptococcus faecalis (enterococci). Gram-negative bacteria: Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Haemophilus influenzae, Proteus is wonderful, Proteus vulgaris, Morganella morganii, providencia spp. (incl. Rettgeri Providence), Serratia spp. (including Serratia marcescens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa and some other Pseudomonas spp., Acinetobacter calcoaceticus, 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., Peptostreptococcus spp., Veillonella spp.), Gram-positive rods (including Clostridium spp., Eubacterium spp. и Lactobacillus spp).

The following sensitivity levels have been established for sulbactam / cefoperazone. IGC (ug / ml), expressed in concentration cefoperazone sensitive microorganisms is less than or equal to 16, for organisms with an intermediate sensitivity is in the interval 17-63, as for resistant – more 64. Zone sensitivity in determining the disco-diffusion method make up: For more sensitive microorganisms 21 mm; with an intermediate sensitivity – from 16 to 20 mm, as for resistant – more 15 mm.

To determine the IPC you can use the serial dilutions sulbactam/zefoperazon ratio 1:1 in a soup or agar Wednesday. To determine the IPC disco-diffusion method, we recommend that you use the disk, comprising 30 g and sulbactam 75 g cefoperazone.

The following quality control standards are recommended when using drive, containing 30 g and sulbactam 75 g cefoperazone. To control strain of Acinetobacter spp. (AS ATCC 43498) the diameter of the zone is 26-32; for Pseudomonas aeruginosa (AS ATCC 27853) – 22-28; for Escherichia coli (AS ATCC 25922) – 27-33; for Staphylococcus aureus (AS ATCC 25923) – 23-30.

Pharmacokinetics

Absorption and distribution

C_max sulbactam and zefoperazon after in/in the dose of Sul'perazona 2 g (1 Mr. and sulbactam 1 g cefoperazone) during 5 min averaged 130.2 ug / ml 236.8 ug / ml, respectively. This reflects higher V_d sulbactam (from 18.0 to 27.6 l) compared with that of cefoperazone (from 10.2 to 11.3 l).

After the / m 1.5 g sulbactam/zefoperazon (500 mg sulbactam, 1 g cefoperazone) C_max sulbactam and zefoperazon in serum were observed in the period from 15 minutes to 2 hours after injection. C_max in serum were 19.0 and 64.2 µg/ml and sulbactam zefoperazon respectively.

As sulbactam, medical products and well distributed in various tissues and body fluids, including bile, gallbladder, skin, appendix, fallopian tubes, ovary, uterus.

There is no pharmacokinetic interaction between cefoperazonom and sulbactam in imposing no Sul'perazona.

When you reapply a meaningful change farmakokineticeskih parameters of both components, no Sul'perazona. With the introduction of the drug every 8-12 h accumulation was observed.

Metabolism and excretion

About 84% doses of sulbactam and 25% dose zefoperazon when introducing Sul'perazona displayed kidneys. The rest of the cefoperazone is derived mainly from the bile. With the introduction of Sul'perazona T_1/2 sulbactam is averaging about 1 no, T_1/2 zefoperazon- 1.7 no. The serum concentration is proportional to the administered dose.

Pharmacokinetics in special clinical situations

Cefoperazone is actively excreted in the bile. T_1/2 cefoperazone is usually lengthened, and excretion in the urine is increased in patients with liver disease and/or obstruction of the biliary tract. Even with severe hepatic impairment in bile achieved therapeutic concentrations of cefoperazone, a T_1/2 increases only 2-4 times.

In patients with varying degrees of kidney dysfunction, receiving Sul'perazon, There was revealed high correlation between total ground clearance and settlement from the organism sulbactam QC. In patients with Terminal renal insufficiency revealed a significant lengthening of T_1/2 sulbactam (average 6.9 and h 9.7 hours in various studies). Hemodialysis causes significant changes in T_1/2, total clearance from the body and V_d sulbactam.

Pharmacokinetics of Sul'perazona was studied in the elderly with renal failure and liver. Compared with healthy volunteers showed an increase in the duration T_1/2, reduction in clearance and increase in V_d as sulbactam, and zefoperazon. The pharmacokinetics of sulbactam correlated with the degree of renal impairment, and pharmacokinetics with zefoperazon degree of human liver.

In studies in children have not revealed significant changes farmakokineticeskih parameters Sul'perazona components as compared to adults. Average T_1/2 sulbactam in children ranged from 0.91 to 1.42 no, zefoperazon-from 1.44 to 1.88 no.

Testimony

Infectious-inflammatory diseases, caused by susceptible to malaria infections:

- Infections of the upper and lower respiratory tract;

-upper and lower divisions of the urinary tract;

- Intra-abdominal infections (incl. peritonitis, cholecystitis, kholangit);

- Sepsis;

- Meningitis;

- Infections of the skin and soft tissues;

- Bone and joint infections;

- Inflammatory diseases of the pelvic organs (incl. endometritis);

- Gonorrhea.

Dosage regimen

In Adult Sul'perazon it is recommended to apply the following daily doses.

Daily dose should be divided into equal parts and enter every 12 no.

At severe or refractory infections daily dose can be increased up to Sul'perazona 8 g component ratio 1:1 (ie. 4 g cefoperazone). Patients, receiving Sul'perazon in the ratio 1:1, may require additional introduction zefoperazon. Dose should be divided into equal parts and enter every 12 no.

The recommended maximum daily dose of sulbactam is 4 g.

In children Sul'perazon it is recommended to apply the following daily doses.

Dose should be divided into equal parts and enter every 6-12 no.

At severe or refractory to treatment infections the dose may be increased up to 160 mg/kg/day when component ratio 1:1. The daily dose is divided into 2-4 equal parts.

In Newborn during the first weeks of life the drug should enter every 12 no. The maximum daily dose of sulbactam in children should not exceed 80 mg / kg / day.

In patients with acute violations of the kidney (CC 15-30 ml / min) the maximum dose of sulbactam 1 g every 12 no (the maximum daily dose of sulbactam – 2 g), and in patients with CC less than 15 ml / min the maximum dose of sulbactam 500 mg every 12 no (the maximum daily dose of sulbactam – 1 g). With heavy infections may require additional introduction zefoperazon. Since the gemodialise farmakokinetika sulbactam greatly varies and is somewhat reduced T_1/2 zefoperazon from whey, introduction of Sul'perazona should be scheduled after dialysis.

If the regular monitoring of serum concentration of zefoperazon not performed, the minimum daily dose should not exceed 2 g.

Rules and application solution for the on/in the introduction

For solution for the infusions of bred 2 g (1 g +1 g) Sul'perazona in the initial amount 6.7 ml of one of the following infusion solutions: 5% solution of dextrose in water, 5% dextrose in solution 0.225% sodium chloride, 5% solution dekstrozy in physiological solution, 0.9% sodium chloride solution or sterile water for injection, and then dilute to 20 ml Starter solution.

For solution for the on/in infusion can be used laktirovannyj ringer's solution, However, it cannot be used for initial dilution, in view of the incompatibility of this mixture. Compatibility can be achieved through a two-stage solution-originally powder dissolved in water for injection, and then diluted solution Ringer lactate concentration to sulbactam 5 mg / ml (2 ml the initial solution diluted in 50 ml Ringer lactate or 4 ml 100 ml of ringer's lactate).

Infusion was performed for 15-60 m.

In/in the injection of the content of each vial should dissolve in 6.7 ml in one of the solvents, as stated above, and enter at least 3 m.

Rules for solution for the on/m introduction

For solution for the on/m introduction you can use 2% lidocaine, However, it should not be used for initial dilution, because of their incompatibility. Compatibility can be achieved through a two-stage solution-originally powder dissolved in water for injection, and then throw 2% lidocaine hydrochloride.

The total volume of solvent 6.7 ml. The final solution will contain medical/sulbactam in the ratio 125 mg/125 mg 1 ml 0.5% lidocaine.

Side effect

Allergic reactions: anaphylactic shock.

From the digestive system: diarrhea, nausea, vomiting, psevdomembranoznыy colitis; transient increased liver-AST, GOLD, Alkaline phosphatase, bilirubin in serum.

Allergic reactions: maculo-papular rash, itch, hives, Stevens-Johnson syndrome (the risk of these reactions is higher in patients with allergic reactions in history).

From the hematopoietic system: reduction in the number of neutrophils, Reversible neutropenia (long-term treatment), reduction of hemoglobin and hematocrit, passing eozinofilia, leukopenia, thrombocytopenia, gipoprotrombinemii; in some cases – Positive Coombs. If you use a solution of Benedict's may occur or false-positive reeakcija for glucose in the urine.

From the urinary system: hematuria.

Local reactions: Sul'perazon is well tolerated in the/m introduction. Sometimes after the/m injection, there has been passing pain, burning at the injection site. When in/with the introduction of Sul'perazona using a catheter may develop flebit at infusion.

Other: headache, fever, chills, vasculitis.

Contraindications

— allergic to Penicillins, sulbactam, medical or any other cephalosporins.

Pregnancy and lactation

Sulbactam and medical products penetrate the placental barrier.

Application of Sul'perazona in pregnancy and lactation is possible only, if the expected benefit to the mother outweighs the potential risk to the fetus or child.

Cautions

Patients, treated with beta-lactam antibiotics, incl. cephalosporins, cases of serious reactions of hypersensitivity (anaphylactic), that sometimes resulted in death. The risk of such reactions is higher in patients, have a history of hypersensitivity reactions have been observed. If you experience an allergic reaction, you must stop the drug and appoint adequate therapy.

Serious anaphylactic reactions need urgent introduction epinephrine (adrenaline). In/in introducing SCS and Suppl, including intubation.

With severe obstruction of the biliary tract, severe liver disease, as well as the human kidney, combined with any of the conditions, may require the correct dosage of the drug.

In patients with impaired liver and related kidney function you must monitor serum concentration zefoperazon and correction dose if necessary. If the regular monitoring of serum concentration of zefoperazon in such cases is not conducted, his daily dose should not exceed 2 g.

When treating cefoperazonom, like other antibiotics, in rare cases, developed a deficiency of vitamin k. The reason for his, probably, is the Suppression of normal intestinal microflora, that synthesizes the vitamin. Risk patients can be referred, receiving poor nutrition, patients with malabsorbziei (eg, mukovystsydoz) and long-staying on/in artificial nutrition. In such cases, as well as in patients, receiving anticoagulants, There is a need to monitor prothrombin time and if there is evidence to appoint vitamin k.

In long-term care Sul'perazonom (like other antibiotics) You may experience the overgrowth of nonsusceptible microorganisms. Patients should be carefully observed during treatment.

With long-term therapy Sul'perazonom periodically monitor the function of internal organs, including the kidneys, liver and blood system. This is especially important for newborns, first of all preterm, and young children.

Overdose

Information on acute toxicity of sodium and sulbactam sodium zefoperazon in humans is limited.

Symptoms: in overdose can expect adverse effects, registered in the use of the drug. Account should be taken of the fact, the high concentration of beta-lactam antibiotics in the cerebrospinal fluid can lead to neurological violations, including seizures.

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

Drug Interactions

When consuming alcohol during treatment and during the cefoperazonom to 5 days after its introduction were registered disul'firamopodobnye effects, characterized by tides, sweating, headache and tachycardia. Similar reactions have been observed when using some other cephalosporin, Therefore, patients must be warned about the possibility of their occurrence in drinking alcohol during treatment Sul'perazonom. Patients, who need artificial feeding (orally or parenterally), solutions should be avoided, containing ethanol.

Pharmaceutical interaction

Solutions Sul'perazona and aminoglycosides should not directly mix, given the pharmaceutical incompatibility between them. If a combined therapy Sul'perazonom and aminoglikozidami, the two drugs injected by successive infusions using separate secondary catheters, and primary catheter good wash solution between the introduction of doses of drugs. The interval between the introduction of the Sul'perazona and aminoglycoside during the day should be as large.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year.

The reconstituted solution should be stored at room temperature; shelf life – 24 no.