Expiration date: 01/2025

Composition and form of issue:

Powder for preparation of solution for intravenous and intramuscular administration 1 Flask:

Cefotaxime 1 g (corresponds to 1, 048 g of Cefotaxime sodium salt) 

in bottles (complete with the solvent in vials) in carton of 1 vial.

Description of dosage form:

White or yellowish-white powder.

Characteristic:

Semi-synthetic antibiotic of cephalosporin group of III generation for parenteral use.

Pharmacokinetics:

In adults-5 minutes after a single I / V administration of 1 g of Cefotaxime concentration in blood plasma is 100 mg / ml. After I/m administration of Cefotaxime in the same dose, the maximum concentration in blood plasma is detected after 0, 5 hours and ranges from 20 to 30 mg / ml.

T1/2 of the drug within 1 h at in/in the introduction and 1-1. 5 hours when the/m introduction.

Binding to plasma proteins (mainly albumin) is an average of 25-40%.

About 90% of the administered dose is excreted in the urine: 50% — in unchanged form and approximately 20% — in the form of metabolite desacetylcefotaxime.

In the elderly (over 80 years) T1 / 2 Cefotaxime increases to 2, 5 hours.

In adults with impaired renal function-the volume of distribution does not change, and T1/2 does not exceed 2, 5 h, even at the last stages of renal failure.

In children, newborns and premature infants, the plasma level of Cefotaxime and the volume of distribution are similar in adults receiving the same dose of the drug in mg / kg. T1 / 2 Cefotaxime ranges from 0, 75 to 1, 5 hours.

In newborns and prematurely born children, the level of Cefotaxime in plasma and the volume of distribution are similar to those in children. The average T1 / 2 Cefotaxime is from 1, 4 to 6, 4 hours.

Description of the pharmacological action:

Cefotaxime acts bactericidal. It is also resistant to the action of most &beta-lactamase.

The drug is usually sensitive: Aeromonas hydrophila Bacillus subtilis Bordetella pertussis Borrelia burgdorferi Moraxella (Branhamella) catarrhalis Citrobacter diversus Clostridium perfringens Corynebacterium diphtheriae Escherichia coli Enterobacter spp. (sensitivity depends on the epidemiology and the level of sustainability in each country) Erysipelothrix insidiosa Eubacterium Haemophilus penitsillinazoobrazuyuschih and nepenitsillinazoobrazute strains, including ampi-R Klebsiella pneumoniae Klebsiella oxytoca Methi-S-Staphylococcus, including penitsillinazoobrazuyuschih and nepenitsillinazoobrazute strains of Morganella morganii Neisseria gonorrhoeae, including penitsillinazoobrazuyuschih and nepenitsillinazoobrazute the Neisseria meningitidis strains Propionibacterium Proteus mirabilis, vulgaris, Providencia Streptococcus pneumoniae, Salmonella, Seratia spp. (sensitivity depends on epidemiology data and the level of resilience in each country) Shigella, Streptococcus spp. Veillonella Yersinia (sensitivity depends on epidemiology data and the level of resilience in each country).

Drug resistant: Acinetobacter baumannii, Bacteroides fragilis Clostridium difficult Enterococcus gram-negative anaerobes Listeria monocytogenes, Methi-R staphylococcus Pseudomonas aeruginosa, Pseudomonas cepacia stenotrophomonas maltophilia.

Indications:

Treatment of infections caused by microorganisms sensitive to the drug:

• respiratory tract infection
  
• urinary tract infections
  
• septicemia, bacteriemia
  
• endocarditises
  
• intra-abdominal infections (including peritonitis)
  
• meningitis (except Listeria) and other CNS infections
  
• skin and soft tissue infections
  
• bone and joint infections
  
• prevention of infections after surgical operations on the gastrointestinal tract, urological and obstetric operations.
  

Contraindications:

hypersensitivity to cephalosporins

for forms containing lidocaine:

• hypersensitivity to lidocaine or other local anesthetics of amide type
  
• intracardiac blockade without an installed pacemaker
  
• severe heart failure
  
• children under the age of 2, 5 years (/m introduction).
  

Application for pregnancy and breastfeeding:

Cefotaxime penetrates the placental barrier.

Studies conducted in animals have not revealed teratogenic effects of the drug. However, the safety of use of Cefotaxime in pregnancy in humans has not been determined, so the drug should not be used during pregnancy.

Cefotaxime penetrates into breast milk, so if necessary, the appointment of the drug breastfeeding should be interrupted.

Side effect:

Anaphylactic reactions: angioedema, bronchospasm, weakness, rarely-anaphylactic shock.

Skin reactions: rash, redness, urticaria. As in the case of other cephalosporins, very rarely can the development of complications such as erythema multiforme, Stevens-Johnson syndrome, toxic skin necrosis.

Gastrointestinal reactions: nausea, vomiting, abdominal pain, diarrhea may occur. As with the appointment of other broad-spectrum antibiotics, diarrhea may be a symptom of enterocolitis, which in some cases is accompanied by the appearance of blood in the stool. A special form of enterocolitis is pseudomembranous colitis (see "Special instructions").

Reactions from the liver: increased liver enzymes (ALT, AST, LDH, GGT, schf) and/or bilirubin.

Reactions from peripheral blood: neutropenia, rarely-agranulocytosis, eosinophilia, thrombocytopenia, in some cases — hemolytic anemia.

Reactions from the kidneys: deterioration of renal function (increase in creatinine), especially when combined with aminoglycosides, very rare cases of interstitial nephritis.

Reactions from the Central nervous system: encephalopathy (in the case of large doses), especially in patients with renal insufficiency.

The reaction of the cardiovascular system: in rare cases — arrhythmia, following bolus administration via Central venous catheter (see "Method of application and dosage").

Other: fever, inflammation at the injection site, superinfection.

In the treatment of borreliosis: response Arisa-Herxheimer (during the first days of treatment), skin rash, itching, fever, leucopenia, increase in level of liver enzymes, shortness of breath and discomfort in the joints.

In addition to the above, you should monitor the speed of drug administration (See. "Dosage and administration"), as well as monitor kidney function in all cases of combined use of Cefotaxime with aminoglycosides.

In patients requiring sodium restriction, the sodium content in the Cefotaxime sodium salt (48, 2 mg/g) should be taken into account. When the duration of treatment (more than 10 days) should monitor the number of leukocytes and, in the case of neutropenia, treatment should be discontinued.

Drug interaction:

Probenecid delays excretion and increases plasma concentrations of cephalosporins.

As in the case of other cephalosporins, Cefotaxime can potentiate the nephrotoxic effect of drugs with nephrotoxic effect.

During therapy with cephalosporins, a positive sample of Coombs may appear.

It is recommended to use glucose oxidase methods to determine blood sugar levels, due to the development of false-positive results when using non-specific reagents.

Compatibility notes: Cefotaxime should not be mixed with other antibiotics, either in the same syringe or in the same infusion solution.

This also applies to aminoglycosides.

For infusion can be used the following solutions (concentration of Cefotaxime 1 g/250 ml): water for injection, 0, 9% sodium chloride solution, 5% dextrose, ringer solution, sodium lactate and: Hemical, Lanosterol, Macrodex 6%, Rheomacrodex 12%, Autofusion V.

Method of application and doses:

V/m, in/in (slow injection or infusion).

Dosage in adults with normal renal function:

With uncomplicated gonorrhea single dose is 0, 5-1 g and is administered once / m.

In uncomplicated infections of moderate severity, Cefotaxime is administered in a single dose of 1-2 g/m or / in, after 8-12 h, thus, the daily dose ranges from 2 to 6 g. 

In severe infections, a single dose is 2 g and is administered in / in 6-8 hours, thus, the daily dose ranges from 6 to 8 g.

In cases where the infection is caused by insufficiently sensitive strains, antibiotic sensitivity test is the only means of confirming the effectiveness of Cefotaxime.

Dosage in adults with impaired renal function:

In cases where the creatinine level is less than 10 ml/min, half of a single dose is used. The interval of administration remains unchanged (see above).

Accordingly, the daily dose will also be reduced by 2 times.

In the cases when Cl creatinine cannot be measured, it is possible to calculate the level of serum creatinine using the Cockroft formula for adults.

For men:

Creatinine Cl (ml/min) = Weight (kg) × (140 ? age) / 72 × creatinine (mg/%)

or:

Weight (kg) × (140 ? age)/0, 814 × creatinine (mmol/l)

For women:

Cl creatinine (ml / min) = 0, 85 × male

For patients on hemodialysis: 1-2 g per day, depending on the severity of the infection. On the day of dialysis, Cefotaxime is administered after dialysis.

In prematurely born children (up to 1 week of life), the daily dose of the drug is 50-100 mg/kg and is administered in / in at intervals of 12 hours.

In prematurely born children (1-4 weeks of life), the daily dose of the drug is 75-150 mg/kg and is administered in / in at intervals of 8 hours.

In children weighing up to 50 kg, the daily dose of the drug is 50-100 mg / kg and is administered in / in or / m at intervals of 6-8 hours.

Note: the daily dose should never exceed 2 g. in the case of severe infections, such as meningitis, may increase the daily dose in 2 times. Q / m introduction to 1% lidocaine is strictly contraindicated in children under 2, 5 years.

Children weighing 50 kg or more, the drug is prescribed in the same dose as adults.

In order to prevent the development of infections before surgery is usually administered 1 g/m or/in with the beginning of anesthesia, with repeated administration through 6-12 h after surgery.

When performing caesarean section at the time of application of the clamps on the umbilical vein in / enter 1 g of the drug, then after 6-12 h re-enter 1 g of Cefotaxime / m or / in.

Method and duration of use: for the/m injection to dissolve Cefotaxime sterile water for injection in amount of 4 ml for 1 g and 10 ml for 2 g. For I/V infusion of 1 or 2 g are dissolved in 40-100 ml of sterile water for injection or infusion solution. Injection of the solution should be carried out slowly for 3-5 minutes, due to the possible development of life-threatening arrhythmias with the introduction of Cefotaxime through the Central venous catheter.

With the/m introduction the contents of the bottle with Cefotaxime can be dissolved in water for injection or 1% lidocaine solution. In the case of lidocaine is strictly contraindicated in/in the introduction of the drug (see "Special instructions").

The duration of treatment is set individually.

Note: it is necessary to provide aseptic conditions when diluting the contents of the vial and preparing the solution (especially if the diluted Cefotaxime is introduced immediately).

Overdose:

There is a risk of developing reversible encephalopathy with high doses of &beta-lactam antibiotics including Cefotaxime. There is no specific antidote.

Special instruction:

Anaphylactic reaction:

• the assignment requires the collection of cephalosporins Allergy history (allergic diathesis, hypersensitivity reactions to beta-lactam antibiotics)
  
• if the patient has developed a hypersensitivity reaction, the treatment should be discontinued
  
• the use of Cefotaxime is strictly contraindicated in patients with a history of hypersensitivity reaction of immediate type to cephalosporins. In case of any doubt, the presence of a doctor at the first administration of the drug is necessary in view of a possible anaphylactic reaction
  
• known cross Allergy between cephalosporins and penicillins, which occurs in 5-10% of cases. In persons who have a history of Allergy to penicillins, the drug is used with extreme caution.
  

Pseudomembranous colitis

In the first weeks of treatment, pseudomembranous colitis may occur, manifested by severe, prolonged diarrhea. The diagnosis is confirmed by colonoscopy and / or histological examination. This complication is regarded as very serious: immediately stop administering Claforan and prescribe appropriate therapy, including oral vancomycin or metronidazole.

When using lidocaine as a solvent, it is necessary to take into account the information provided in the section "Contraindications".

Shelf life of solutions after dilution

For I/m injection: sterile powder of Cefotaxime after dilution in water or 0 5 or 1% solution of lidocaine hydrochloride is chemically stable for 8 hours (with room temperature not exceeding 25 °C) or for 24 h (at the temperature of 2-8 °C, protected from light).

For injections or infusions when dissolved with water for injection: for 12 h (at room temperature not above +25 °C) or for 24 h (at a temperature of 2-8 °C, in a dark place). Pale yellow tint of the solution does not mean a decrease in antibiotic activity.

For infusion in the infusion solutions are: sterile powder of Cefotaxime chemically stable for 8 h after dilution in a solution of Haemaccel, Lanosterol or Autofusion, and for 6 h after dilution in 10% glucose solution, Macrodex or Rheomacrodex.