Cefobide - instructions for use, doses, side effects, contraindications

Cefoperazone is a semi-synthetic cephalosporin antibiotic with a broad spectrum of action intended only for parenteral administration. The bactericidal action of cefoperazone is due to inhibition of bacterial cell wall synthesis. Cefoperazone active in vitro for a large number of different clinically relevant microorganisms. Resistant to the action of many beta-lactamases. The following microorganisms are susceptible to cefoperazone:

Gram-positive microorganisms:

Staphylococcus aureus, strains that produce and do not produce penicillinase Staphylococcus epidermidis

Streptococcus pneumoniae (before Diplococcus pneumoniae)

Streptococcus pyogenes (beta-hemolytic streptococcus groups A)

Streptococcus agalactiae (beta-hemolytic streptococcus group B)

Streptococcus faecalis (enterococcus)

Beta-hemolytic streptococci

Gram-negative microorganisms:

Escherichia coli

Klebsiella spp.

Enterobacter spp.

Citrobacter spp.

Haemophilus influenzae

Proteus mirabilis

Proteus vulgaris

Morganella morganii (before Proteus morganii)

Providencia rettgeri (before Proteus rettgeri) Providencia spp.

Serratia spp. (including S. marcescens) Salmonella and Shigella spp.

Pseudomonas aeruginosa and some others Pseudomonas

Acinetobacter calcoaceticus

Neisseria gonorrhoeae

Neisseria meningitidis

Bordetella pertussis

Yersinia enterocolitica

Anaerobic microorganisms:

Gram-positive and gram-negative cocci (including Peptococcus spp., Peptostreptococcus spp. and Veillonella spp.)

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

Gram-negative sticks (including Fusobacterium spp., many strains Bacteroides fragilis and others representatives Bacteroides spp.)

Pharmacokinetics:High concentrations in serum, bile and urine are achieved after a single application of the drug. The table shows the concentrations of cefoperazone in the blood serum of adult healthy volunteers after a 15-minute uniform intravenous (IV) infusion of 1, 2, 3 or 4 g of the drug, or a single intramuscular (IM) administration of 1 or 2 g of the drug.

Mean concentrations of cefoperazone in the blood serum (μg / ml)

Dose, route of administration	0*	30 min	1 h	2h	4h	8h	12 h
1 g of IV	153	114	73	38	16	4	0,5
2 g IV	252	153	114	70	32	8	2
3 g IV	340	210	142	89	41	9	2
4 g IV	506	325	251	161	71	19	6
1 g in and	32**	52	65	57	33	7	1
2 g IM	40**	69	93	97	58	14	4

* time elapsed after drug administration, 0 - time corresponding to the end of drug administration; ** results obtained 15 minutes after drug administration.

The average half-life of cefoperazone from serum is approximately 2 hours and does not depend on the mode of administration.

Cefoperazone achieves therapeutic concentrations in all the fluids and tissues in the body, including ascites and cerebrospinal fluid (with meningitis), urine, bile and gallbladder wall, sputum and lungs, palatine tonsils and sinus mucosa, atrial, kidney, ureter, prostate, testicles,uterus and fallopian tubes, bones, cord blood and amniotic fluid.

Cefoperazone is excreted by the kidneys and with bile. Usually the concentration of the drug in the bile reaches a maximum 1 to 3 hours after administration and exceeds the concentration in the blood serum 100 times. The concentration of cefoperazone in bile varies from 66 μg / ml after 30 minutes to 6,000 μg / ml 3 h after iv bolus administration of 2 g of the drug to patients not suffering from blockage of the bile ducts.

In patients with normal renal function, an average of 20-30% of cefoperazone is excreted through the kidneys 12 hours after the administration of different dosages in various ways. After a 15-minute IV infusion of 2 g of cefoperazone, the concentration of the drug in the urine exceeded 2200 μg / ml. After iv administration and 2 g of the drug, the maximum concentrations in the urine were approximately 1000 μg / ml.

In healthy people, repeated administration of cefoperazone does not result in cumulation.

Application for hepatic and / or renal insufficiency

In patients with liver disease or biliary duct obstruction, the half-life of cefoperazone from serum usually lengthens, and the excretion of the drug by the kidneys increases.But even with severe violations of liver function in bile, therapeutic concentrations of cefoperazone are achieved, and the half-life is only 2-4 times longer

The maximum concentrations in the blood serum, the area under the concentration-time curve (AUC) and the half-life period from serum are the same in healthy people and in patients with renal insufficiency.

In patients with renal-hepatic insufficiency cefoperazone can accumulate in the blood serum.

Indications:

Monotherapy

Cefoperazone is indicated for the treatment of the following infectious diseases caused by susceptible 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

- Septicemia

- Meningitis

- Infections of the skin and soft tissues

- Infections of bones and joints

- Inflammatory diseases of the pelvic organs, endometritis, gonorrhea and other genital tract infections

Prof. infectious postoperative complications with abdominal, gynecological, cardiovascular and orthopedic operations.

Combination Therapy

A wide spectrum of action of cefoperazone allows for monotherapy of most infections, however, in the presence of indications cefoperazone can also be used in combination with other antibiotics.

Contraindications:Hypersensitivity to cefoperazone, as well as allergic reactions to cephalosporins in the anamnesis.

Carefully:Obstruction of the bile ducts, severe hepatic insufficiency, renal failure, simultaneous damage to the liver and kidneys (see section "Method of administration and dose").

Pregnancy and lactation:Controlled studies on the effect of the drug on pregnant women were not conducted. Use in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. A small amount of cefoperazone is excreted in breast milk. Caution should be exercised when using cefoperazone in nursing mothers.

Dosing and Administration:

Adults

2-4 g / day, divided into two injections, every 12 hours. In severe infections, the dose can be increased to 8 g / day, divided into two injections, every 12 hours.When a dose of 12 g / day or even 16 g / day was given in equal parts in 3 divided doses every 8 hours, no complications were found. Therapy can begin before the results of sowing and other laboratory tests.

In uncomplicated gonococcal urethritis, a single intramuscular injection of 500 mg of the drug is recommended.

The drug is injected intramuscularly into the large gluteus muscle or the anterior surface of the thigh.

When i / in the jet slow introduction, the maximum single the dose of the drug is 2 g; duration of administration - at least 3-5 minutes. The duration of IV infusion is 15-60 minutes.

Prevention of postoperative complications

Apply 1 g or 2 g of IV in 30-90 minutes before the operation. If necessary, the administration of the drug can be repeated every 12 hours (in most cases for no more than 24 hours). In case of operations with an increased risk of infection (for example, in colorectal surgery), or if the infection is particularly dangerous (for example, in open-heart surgery or joint replacement), the drug can be prevented for 72 hours after the operation is completed.

When a violation of liver function

Correction of the dose may be required in case of severe obstruction of the bile duct, severe hepatic insufficiency or with concomitant renal dysfunction. The daily dose should not exceed 2 g, while there is no need to monitor the concentration of the drug in the blood serum.

In case of impaired renal function

Because the cefoperazone is mainly excreted not through the kidneys, then when applied in therapeutic doses (2-4 g / day), dose adjustment is not required. For patients who have a glomerular filtration rate below 18 ml / min or a serum creatinine concentration above 3.5 mg / dL, the daily dose should not exceed 4 g. When hemodialysis, the half-life of cefoperazone decreases slightly, so the drug should be administered after the end dialysis.

When the liver and kidney function is impaired

In the case of a simultaneous violation of the liver and kidneys, you should monitor the concentration of cefoperazone in the blood serum and, if necessary, adjust the dose. If the daily dose does not exceed 2 g, there is no need to monitor serum concentrations.

Use in children

50-200 mg / kg of body weight / day in equal parts every 8-12 hours.The maximum dose should not exceed 12 g / day.

With intravenous infusion of slow injection, the maximum single dose is 50 mg / kg of body weight; duration of administration - at least 3-5 minutes.

Application in newborns (age less than 8 days)

50-200 mg / kg of body weight / day. The daily dose is administered in equal portions every 12 hours.

Preparation of solutions

Intramuscular injection

To prepare solutions, sterile or bacteriostatic water for injections is used. If it is necessary to prepare a solution with a concentration of 250 mg / ml or more, a lidocaine solution is recommended for dilution, which is prepared by diluting 2% lidocaine solution in sterile water for injection (approximate concentration of lidocaine hydrochloride in the resulting solution is 0.5%). It is recommended to dilute the drug in two stages: 1) first add the necessary amount of sterile water for injection and shake until the powder is completely dissolved, 2) then add the necessary amount of 2% lidocaine solution and mix.

The final concentration of cefoperazone

1 stage Sterile water volume

2 stage

Volume of 2% of lidocaine

Entered volume *

250 mg / ml

2.6 ml

0.9 ml

4.0 ml

333 mg / ml

1.8 ml

0.6 ml

3.0 ml

* Excess volume allows to completely fill the syringe of the specified volume.

Intravenous administration

General recommendations

The preparation of the solution is carried out in two stages:

- The contents of the vial are first diluted in any of the following compatible solutions for intravenous administration (at a rate of at least 2.8 ml per 1 g of cefoperazone):

- 5% dextrose solution for injection,

- 10% dextrose solution for injection,

- 5% dextrose solution in a 0.9% solution of sodium chloride for injection,

- 0.9% solution of sodium chloride for injection,

- Normosol M in a 5% solution of dextrose for injection,

- 5% dextrose solution in 0.2% solution of sodium chloride for injection,

- Normosol R,

- sterile water for injections.

To facilitate dissolution, it is recommended to use 5 ml of solvent per 1 g of cefoperazone.

2. Then the entire amount of the resulting solution is further diluted in one of the following solutions:

- 5% dextrose solution for injection,

- 10% dextrose solution for injection,

- 5% dextrose solution in Ringer's lactate solution for injection,

- Ringer's lactate solution,

-0,9% solution of sodium chloride for injection,

- 5% dextrose solution in a 0.9% solution of sodium chloride for injection,

- Normosol M in a 5% solution of dextrose for injection,

- Normosol R,

- 5% dextrose solution in 0.2% solution of sodium chloride for injection.

Intravenous drip introduction

The contents of one vial are dissolved in 20-100 ml of a compatible sterile solution for

in / in injections. Infusion is carried out for 15 minutes to 1 hour. When applied as aof the solvent of sterile water for injection, its volume should not exceed 20 ml.

Prolonged intravenous infusion

The contents of one vial (1 g) are dissolved in 5 ml of sterile water for injection or bacteriostatic water for injection; the resulting solution is added to the corresponding solution for iv administration.

Intravenous Jet Slow Injection

The maximum dose of cefoperazone should not exceed 2 g per administration in adults and 50 mg / kg of body weight in children. The drug is dissolved in a suitable solvent (final concentration of 100 mg / ml) and injected for at least 3-5 minutes.

Side effects:

Frequency of adverse reactions according to WHO classification:

Often: >10%

Often: >1% and <10%

Infrequently: >0.1% and <1%

Rarely: >0.01% and <0.1%

Rarely: <0,01 %

Frequency unknown It is impossible to determine from the available data

From the side digestive system *: often - diarrhea; infrequently - nausea, vomiting; rarely - pseudomembranous colitis.

From the hepatobiliary system: often - jaundice.

Allergic reactions: often hypersensitivity reactions; infrequently - drug fever; rarely anaphylactoid reactions (including shock).

Laboratory indicators: Often - eosinophilia, a decrease in hemoglobin or

hematocrit; often - neutropenia, positive line The Coombs antiglobulin test, an increase activity alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase, a transient increase in the concentration of urea nitrogen, creatinine in the blood plasma; rarely - hypoprothrombinemia; rarely - thrombocytopenia.

From the skin: often- Maculopapular rash, hives, itching; rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome.

Local reactions: often - phlebitis at the injection site (with intravenous infusion through the catheter); infrequently Pain at the injection site.

From the cardiovascular system: rarely - bleeding.

* - in all cases, these phenomena succumbed to symptomatic therapy or disappeared after its termination.

Overdose:

Information on acute toxicity of cefoperazone is limited. It is assumed that an overdose of the drug can cause effects, mainly being a more pronounced manifestation of the side effect of the drug. Given that high concentrations of beta-lactam antibiotics in cerebrospinal fluid can cause neurologic effects, one should remember the possibility of developing seizures in overdose. In the case of an overdose of the drug in patients with renal insufficiency, hemodialysis can help remove the drug from the body.

Treatment: sedative therapy with the use of diazepam in epileptic seizures caused by overdose.

Interaction:

Alcohol

When alcohol was taken during or within 5 days after the administration of cefoperazone, a disulfiram-like reaction was reported, manifested in the form of hot flashes, increased sweating, headache and tachycardia. Patients should be warned about the danger of taking alcohol during the application of cefoperazone. For patients who are on oral or parenteral artificial feeding, solutions containing alcohol should be excluded.

Laboratory Tests

False positive reaction to glucose in urine is possible when using solutions

Benedicta (Benedict's) or Feeling (Fehling's).

Probenicides

Probenicid does not affect the concentration of cefoperazone in the blood serum.

Incompatibility

Aminoglycosides

Solutions of cefoperazone and aminoglycoside should not be mixed directly, because there is a physical incompatibility between them. If it is necessary to carry out combined therapy with cefoperazone and aminoglycoside, it is prescribed as a sequential iv drip infusion using two separate catheters, provided that they are adequately washed with appropriate solvents between the administration of consecutive doses of the drugs. Cefoperazone should be administered before the administration of the aminoglycoside.

When treating aminoglycosides, it is recommended to monitor kidney function.

Special instructions:Hypersensitivity

There have been reports of serious (in some cases, lethal outcome) reactions

hypersensitivity (anaphylactic reactions) in patients who received beta-lactam antibiotics or cephalosporins, including cefoperazone. These reactions are more typical for patients who had hypersensitivity reactions to several allergens earlier. Before using cefoperazone, it is necessary to determine whether the patient has previously had an increased sensitivity to cephalosporins, penicillins and other drugs. In patients from hypersensitivity to penicillin, the drug should be used with great care. In all patients with a tendency to various allergic reactions in the anamnesis (in particular to the drug allergies), antibacterial drugs should be used with caution. If an allergic reaction occurs, cefoperazone should be discontinued and appropriate treatment initiated. Serious anaphylactic reactions require immediate administration epinephrine. If necessary, apply oxygen, intravenous glucocorticosteroids, and support for respiratory function, including intubation.

General instructions

In some patients, treatment with cefoperazone, as well as treatment with other antibacterial

drugs, can lead to a deficiency in the body of vitamin K. This is probably due to the suppression of the intestinal flora that synthesizes this vitamin.Such a risk is susceptible to patients with malabsorption (for example, caused by cystic fibrosis), as well as patients who adhere to a defective diet or who are for a long time on parenteral nutrition. In such patients, prothrombin time, if necessary, to prescribe vitamin K. As with other antibiotics, prolonged use of cefoperazone can lead to increased growth of resistant microorganisms, so during treatment patients should be under strict medical supervision. With prolonged therapy, it is recommended periodically monitor the performance of internal organs, including the kidneys, liver and hematopoiesis system. This is especially important for newborns, especially premature and small children. Diarrhea associated with Clostrifium difficile is observed against the background of almost all antibacterial drugs, including cefoperazone, and is manifested from mild forms of diarrhea to severe colitis with lethal outcome. Treatment with antibacterial drugs leads to damage to the normal microflora of the colon, resulting in an increased growth of Clostrifium difficile. FROM.difficile produces toxins A and B, leading to the development of diarrhea associated with Clostrifium difficile. Hypertoxin-producing strains of Clostrifium difficile cause an increase in morbidity and mortality, as the infections caused by these strains can be refractory to ongoing antibiotic therapy and may require a colonectomy. All cases of diarrhea in patients with antibiotic therapy should be considered as suspicious for the development of diarrhea associated with Clostrifium difficile. It is necessary to carefully collect the anamnesis in case of the development of diarrhea associated with Clostrifium difficile within 2 months after the appointment of antibacterial drugs.

Neonatal application

Cefoperazone is successfully used in the treatment of newborns. If you need to use the drug for premature and newborn children, you should consider both the expected positive effects and the possible risk associated with treatment. In newborns with nuclear jaundice cefoperazone does not displace bilirubin from the bonds with plasma proteins.

Stability of solutions

The following solvents and exemplary concentrations of cefoperazone ensure the stability of the solution under the following conditions and for the specified periods of time.After expiration of the indicated periods of storage, unused residues of solutions should be destroyed.

At a temperature of 15 ° - 25 ° C - during 24 h.	Approximate concentrations
5% dextrose solution in Ringer's solution lactate for injection	2-50 mg / ml
10% solution dextrose for injections At a temperature of 15 ° - 25 ° C - within 24 hours or in the refrigerator (2 ° - 8 ° C) - within 5 days	2-50 mg / ml
Bacteriostatic water for injections	300 mg / ml
5% dextrose injection solution	2-50 mg / ml
5% dextrose solution in a 0.9% solution of sodium chloride for injection	2-50 mg / ml
5% dextrose solution in 0.2% solution Sodium Chloride For Injection	2-50 mg / ml
Ringer's solution lactate for injection	2 mg / ml
0.5% lidocaine for injection	300 mg / ml
0.9% solution of sodium chloride for injection	2-300 mg / ml
Normosol M in a 5% solution of dextrose for injection	2-50 mg / ml
Normosol R	2-50 mg / ml
Sterile water for injections	300 mg / ml

The reconstituted solutions are stored in glass or plastic syringes, glass or flexible plastic containers intended for parenteral solutions.

In the freezer (from -20 ° to -10 ° C) - for 3 weeks
5% dextrose injection solution	50 mg / ml
5% dextrose solution in 0.9% solution of sodium chloride for injection	2 mg / ml
5% dextrose solution in 0.2% solution of sodium chloride for injection	2 mg / ml
In the freezer (-20 ° to -10 ° C) - for 5 weeks
0.9% solution of sodium chloride for injection	300 mg / ml
Sterile water for injections	300 mg / ml

In the freezer, the reconstituted solutions are stored in plastic syringes or flexible plastic containers intended for parenteral solutions.

Before use, frozen drug solutions are thawed at room temperature. Unused thawed solution must be destroyed. Do not refreeze the solution.

Effect on the ability to drive transp. cf. and fur:Experience in the use of the drug in clinical practice indicates that the deterioration of the ability to drive and control machinery during the period of cefoperazone is unlikely.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection 1 g.

Packaging:1 g of cefoperazone per bottle of clear, colorless glass of Class III (Hebrew Pharm.), Sealed with a halogen-butyl rubber stopper, latex-free, crimped with an aluminum cap with a plastic protective cap of the flip-off type. 1 bottle with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 of the year. Do not use after the expiry date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:P N008921

Date of registration:07.06.2010

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

HAUPT PHARMA LATINA, S.R.L. Italy

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp27.10.2015

Illustrated instructions

Instructions

Cefobide (Cefobid)