Sulceph - instructions for use, dose, side effects, contraindications

Cefoperazone is a third generation cephalosporin that acts on sensitive microorganisms during their active propagation by inhibiting the biosynthesis of the cell wall mucopeptide. Sulbactam does not have clinically significant antibacterial activity (except for Neisseriaceae and Acinetobacter), is an irreversible inhibitor of most major beta-lactamases that produce microorganisms resistant to beta-lactam antibiotics. Sulbactam also binds to some penicillin-binding proteins, so the combination of cefoperazone and 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 spp., Staphylococcus spp., Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.

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, Streptococcus faecalis.

Gram-negative microorganisms:

Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus vulgaris, Providencia rettgeri, Providencia spp., Serratia spp. (including S. marcescens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Yersinia enterocolitica.

Anaerobic microorganisms z Bacteroides fragilis, Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Veillonella spp., Clostridium spp., Eubacterium spp., Lactobacillus spp.

Pharmacokinetics:

Cefoperazone and sulbactam are well distributed into various tissues and fluids, including bile, gall bladder, skin, appendix, fallopian tubes, ovaries, uterus, etc.

The maximum concentrations of cefoperazone and sulbactam after intravenous administration of 2 g of the drug for 5 minutes averaged 130.2 and 236.8 μg / ml, respectively. The volume of distribution of sulbactam from 18.0 to 27.6 liters, of cefoperazone - from 10.2 to 11.3 liters. About 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.

The half-life of cefoperazone averages about 1.7 h, sulbactam - 1 h. The serum concentration of cefoperazone and sulbactam is proportional to the administered dose.

With repeated administration, the pharmacokinetic properties of the drug do not change. With the introduction of the drug every 8-12 hours cumulation is not observed.

Pharmacokinetics for violations 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 by 2-4 times.

Pharmacokinetics for renal dysfunction:

In patients with varying degrees of renal dysfunction, receiving the drug, 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 6.9-9.7 hours in various studies) was detected.Hemodialysis causes significant changes in the half-life, total clearance from the body and the volume of distribution of sulbactam.

Pharmacokinetics in the elderly:

In elderly people with renal insufficiency and impaired liver function, an increase in the half-life period, a decrease in clearance and an increase in the volume of distribution of both sulbactam and cefoperazone are observed. The pharmacokinetics of sulbactam correlates with the degree of renal dysfunction, and the pharmacokinetics of cefoperazone - with the degree of impaired hepatic function.

Pharmacokinetics in children:

Children have no significant differences in the pharmacokinetics of the components of the drug compared to adults. The average half-life of sulbactam in children is from 0.91 to 1.42 h, of cefoperazone from 1.44 to 1.88 h.

Indications:

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

- infections of the upper and lower respiratory tract;

- urinary tract infections;

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

- septicemia;

- meningitis;

- infections of the skin and soft tissues;

- infection of bones and joints;

- infection of the urinary tract (inflammatory diseases of the pelvic organs, endometritis, gonorrhea).

Contraindications:Hypersensitivity to penicillins, sulbactam, cefoperazone, incl. to other beta-lactam antibiotics.

Carefully:Severe violations of kidney and liver function, colitis (including in the anamnesis), premature newborns.

Pregnancy and lactation:During pregnancy and during breastfeeding the drug is used only if the expected benefit for the mother exceeds the potential risk to the fetus and newborn.

Dosing and Administration:

Intravenous or intramuscular.

Adults - 2-4 g / day with an interval of 12 hours; with severe, persistent infections - 8 g / day. The maximum daily dose is 8 g.

Patients with chronic renal insufficiency (CRF) (creatinine clearance less than 30 ml / min) - dose adjustment: Q 15-30 ml / min - 1 g 2 times a day, CC less than 14 ml / min - 500 mg 2 times a day.

A dose change may be required in case of severe obstruction of the biliary tract, severe liver disease. In patients with impaired liver function and concomitant renal dysfunction, monitoring of serum concentration of cefoperazone and correlation of its dose should be necessary if 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.

Children - 40-80 mg / kg / day in 2-4 injections; with severe, long-lasting infections, at 160 mg / kg / day. The maximum daily dose is 160 mg / kg / day. 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.

Newborns should be injected every 12 hours during the first week of life.

For intravenous administration, the contents of the vial are dissolved in an adequate volume of 5% dextrose solution, 0.9% solution of sodium chloride for injection or sterile water for injection, diluted to 20 ml with the same solution and injected for 15-60 minutes; intravenous injection - 3 min; for intramuscular injection, sterile water for injection is used for dissolution. To obtain a concentration of cefoperazone 250 mg / ml and more dilution is carried out in 2 stages: sterile water, then 2% lidocaine solution to obtain a 0.5% solution of lidocaine.

Side effects:

The cardiovascular system: lowering blood pressure.

Gastrointestinal tract: diarrhea, nausea, vomiting, pseudomembranous colitis.

Allergic reactions: maculopapular rash, hives, itching, Stevens-Johnson syndrome, anaphylactic shock. The risk of reactions is higher in patients with allergic reactions in the anamnesis.

The system of hematopoiesis: decrease in the number of neutrophils. With long-term treatment, reversible neutropenia develops, a decrease in hemoglobin and hematocrit, transient eosinophilia, leukopenia, thrombocytopenia, as well as hypoprothrombinemia, hypercreatinemia, anemia, and bleeding.

Laboratory indicators: increased activity of "hepatic" transaminases - aspartate aminotransferase (ACT), alanine aminotransferase (AJ1T), alkaline phosphatase, bilirubin in blood serum, hematuria. In some patients, a false positive Coombs test was observed during treatment.

Local Reactions: after intramuscular injection, transient pain is possible. With intravenous administration of the drug with the help of a catheter, phlebitis can develop at the site of infusion.

Other: headache, fever, chills, vasculitis.

Overdose:

Symptoms: neurological disorders, including convulsions.

Treatment: sedative therapy. Effective hemodialysis, especially in patients with impaired renal function.

Interaction:Ethanol

When drinking alcohol during treatment with the drug and for the next 5 days after its administration, disulfiram-like reactions characterized by "hot flashes", sweating, headache and tachycardia were recorded, so patients should be warned about the possibility of their appearance when drinking alcoholic beverages against the background of drug treatment. Patients who need artificial feeding (inside or parenteral) should avoid using solutions containing ethanol.

Aminoglycosides

Solutions of the drug and aminoglycosides should not be mixed, given the pharmaceutical incompatibility between them. If combined therapy with the drug and aminoglycoside is carried out, the two drugs are administered by successive infusions using separate secondary catheters, and the primary catheter is washed with an adequate solution between doses of the drugs. Intervals between the administration of the drug and aminoglycoside throughout the day should be as large as possible.

Loop diuretics

Joint use of the drug with loop diuretics can lead to the development of nephrotoxic action.

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. Incompatible with Ringer's solution, 2% lidocaine solution (initial use of water for injection leads to the formation of a compatible mixture).

Special instructions:

When allergic reactions occur, it is necessary to cancel the drug and prescribe adequate therapy.

In the treatment of cefoperazonom in rare cases, vitamin K deficiency develops. Its cause is probably suppression of normal intestinal microflora, which synthesizes this vitamin. 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 is possible. Patients should be carefully observed during treatment.

With prolonged therapy, it is recommended to periodically monitor the performance of internal organs, including the kidneys, liver and hematopoiesis system. This is especially important in the treatment of newborns, especially premature babies, and small children.

With the simultaneous use of aminoglycosides, kidney function should be monitored.

With severe obstruction of the biliary tract, severe hepatic insufficiency, a dose change and control of the concentration of cefoperazone in the serum (maximum daily dose - 2 g) is necessary.

Treatment of premature newborns is carried out if the possible benefits

exceeds the potential risk.

Effect on the results of laboratory tests.

When using a solution of Benedict or Felling, a false-positive reaction to glucose in the urine can be observed. Possible false positive test Coombs.

Effect on the ability to drive transp. cf. and fur:The drug does not affect the ability to drive vehicles and maintain machinery.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection 1 g + 1 g.

Packaging:

By 2.18 grams of powder in glass bottles of colorless glass, sealed with rubber stoppers, coated with aluminum caps.

One bottle together with the instruction for use is placed in a cardboard box or 100 bottles (for hospitals) together with instructions for use in a cardboard box.

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:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001677

Date of registration:28.12.2011

The owner of the registration certificate:Medocemi Co., Ltd.Medocemi Co., Ltd. Cyprus

Manufacturer: & nbsp

MEDOCHEMIE, Ltd. Cyprus

Representation: & nbspMEDOKEMI LTD. MEDOKEMI LTD. Cyprus

Information update date: & nbsp26.10.2015

Illustrated instructions

Instructions

Sulceph (Sulcef)