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

Semisynthetic antibiotic group of third generation cephalosporins for parenteral use. Cefotaxime acts bactericidal due to disruption of bacterial wall synthesis. It is also resistant to the action of most B-lactamases. TO cefotaxime are usually sensitive: Aeromonas hydrophila; Bacillus subtilis; Bordetella pertussis; Borrelia burgdorferi; Moraxella (Branhamella) catarrhalis; Citrobacter diversus *; Citrobacter freundii *; Clostridium perfringens;

Corynebacterium diphtheriae; Escherichia coli; Enterobacter spp. *; Erysipelothrix insidiosa; Eubacterium spp .; Haemophilus spp. (penicillinase-producing and non-producing strains, including ampicillin-resistant strains); Klebsiella pneumoniae; Klebsiella oxytoca; Staphylococcus spp. (methicillin-sensitive, including penicillinase-producing and non-penicillinase-producing strains); Morganella morganii; Neisseria gonorrhoeae (including strains producing and not producing penicillinase); Neisseria meningitidis; Propionibacterium spp .; Proteus mirabilis, Proteus vulgaris; Providencia spp .; Streptococcus spp. (including Streptococcus pneumonia), Salmonella spp .; Serratia spp. *; Shigella spp .; Veillonella spp .; Yersinia spp. *, Pscudomonas spp. (except Pseudomonas aeruginosa, Pseudomonas cepacia).

* - sensitivity depends on epidemiological data and on the level of resistance in each country.

Cefotaxime is resistant to: Acinetobacter baumanii, Bacteroides fragilis; Clostridium difficile; Enterococcus spp .; gram-negative anaerobes; Listeria monocytogenes, Staphylococcus spp. (methicillin-resistant strains); Pseudomonas aeruginosa, Pseudomonas cepacia; Stenotrophomonas maltophilia.

Pharmacokinetics:

Have of adults - 5 minutes after a single intravenous (iv) injection of 1 g of cefotaxime, the maximum concentration (C_m_Oh) in the blood plasma is 100 μg / ml.

After intramuscular (intramuscularly) administration of cefotaxime in the same dose FROMmах in a blood plasma is reached through 0,5 ч and makes from 20 up to 30 mkg / ml. Bioavailability of cefotaxime in the / in the introduction is 100%, with the / m introduction - 90-95%. The half-life (T_1/2) of cefotaxime is 1 hour with intravenous administration and 1-1.5 hours with a / m introduction. The binding with plasma proteins (mainly albumins) averages 25-40%. Metabolised in the liver with the formation of an active metabolite deacetylcefotaxime (M1), possessing antibacterial activity, and inactive metabolites (M2, M3). About 90% of the administered dose is excreted by the kidneys: 50% - unchanged, about 15-25% in the form of metabolite deacetylcefotaxime and 15-30% in the form of inactive metabolites (M2 + M3). 10% from the administered dose is excreted by the intestine.

Have elderly patients over 80 years old T_1/2 cefotaxime increases to 2.5The volume of distribution (Vd) is not changes in comparison with the young healthy volunteers.

In adults with impaired function kidneys Vd does not change, but T_1/2 not exceeds 2.5 hours even on the last stages of renal failure.

Children concentration of cefotaxime in plasma and Vd are similar that of adults receiving the same dose of the drug in mg / kg masses. T_1/2 cefotaxime is from 0.75 to 1.5 h.

In newborns and prematurely born children concentration cefotaxime in the blood plasma and Vd similar to those of children. Average T_1/2 cefotaxime ranges from 1.4 to 6.4 h.

Indications:

Cefotaxime is intended for the treatment of infections caused by microorganisms that are sensitive to the drug.

respiratory tract infections;

urinary tract infections;

septicemia, bacteremia;

endocarditis;

intra-abdominal infections (including peritonitis);

meningitis (with the exception of listeriosis) and other CNS infections;

infections of the skin and soft tissues;

infection of bones and joints;

Prevention of infections after surgery on the gastrointestinal tract, urological and obstetric-gynecological operations.

Contraindications:

- Hypersensitivity to cefotaxime, other cephalosporins.

- For forms containing lidocaine as a solvent:

- hypersensitivity to lidocaine or other local anesthetic of the amide type;

- intracardiac blockades without an established pacemaker;

- severe heart failure;

- intravenous administration;

- Children under the age of 2.5 years (intramuscular injection).

Carefully:

- Patients with a history of allergy to penicillins (risk of developing

cross-sectional allergic reactions, see section "Special instructions").

- With simultaneous use with aminoglycosides (see sections "Special instructions",

"Interaction with other drugs").

- In case of renal insufficiency (see section "Method of administration and dose").

Pregnancy and lactation:

Pregnancy

Cefotaxime penetrates the placental barrier. Studies conducted on animals did not reveal a teratogenic or fetotoxic effect of the drug. However, security applications

cefotaxime in pregnancy in humans is not established, so the drug should not be used during pregnancy.

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

Dosing and Administration:

Intramuscularly or intravenously. The dose, mode and frequency of administration should be determined by the severity of the infection, the sensitivity

the pathogen and the patient's condition. Treatment should be started before receiving the results of the sensitivity test. Adults and children over 12 years of age and weighing 50 kg or more for infections of mild and moderate severity - 1 g every 12 h. The dose may vary depending on the severity of the infection, the sensitivity of the pathogen and the patient's condition. When severe infections the dose can be increased to 12 g per day, divided into 3-4 injections.

When infections caused by Pseudomonas spp, the daily dose should be more than 6 g. For children under 12 years and with a body weight of up to 50 kg, the usual dose is 100-150 mg / kg body weight per day, divided into 2-4 injections. When very serious infections the dose can be increased to 200 mg / kg of body weight per day. For newborns, the dose is 50 mg / kg of body weight per day, divided into 2-4 injections. When severe infections - a dose of 150-200 mg / kg of body weight per day, divided into 2-4 injections.

When gonorrhea: 1 g once-intramuscularly or intravenously.

With the aim of prevention of infection before surgery (from 30 to 90 minutes before the operation) 1 g intramuscularly or intravenously. When implementation of cesarean section at the time of application of the clips to the umbilical vein, 1 g of the drug is intravenously injected, then 1 g intramuscularly or intravenously is reintroduced after 6-12 h.

Patients with renal disease insufficiency

In cases where creatinine clearance is less than 10 ml / min, it is necessary to reduce the dose. After the introduction of the initial single dose, the daily dose should be halved without changing the frequency of administration, that is, instead of 1 g every 12 hours - 0.5 g every 12 hours, instead of 1 g every 8h- 0.5 g every 8 h, instead of 2 g every 8 h - 1 g every 8 h, etc. A further dose adjustment may be required depending on the course of the infection and the general condition of the patient.

Rules for the preparation of solutions For intravenous injection, water for injection is used as the solvent (1 g diluted in 4 ml); with intravenous injection, the solution should be injected for 3 to 5 minutes.

For intravenous infusion, a solvent is used 0,9% solution of sodium chloride or 5% dextrose solution (1 -2 g diluted in 40- 100 ml of solvent). Ringer's solution can also be used lactate. Duration infusion - 20-60 min.

For intramuscular introduction of use water for injection or

1% lidocaine solution (1 g bred in 4 ml of solvent).

Side effects:

Classification of undesirable adverse reactions according to the frequency of development, according to recommendations

World Health Organization: very often (>10 %); often (>1% and <10%); infrequently (>0,1 %

and <1%); rarely (>0.01% and <0.1%); very rarely (<0.01%); the frequency is unknown (based on the available data it is impossible to estimate the incidence of side effects).

Infectious and parasitic diseases

Frequency unknown: superinfection.

As with the appointment of other antibiotics, the use of cefotaxime, especially prolonged, can lead to an excessive growth of insensitive microorganisms. Regular monitoring of the patient's condition should be made. If the development of superinfection occurs during therapy with cefotaxime, appropriate measures should be taken.

Violations of the blood and lymphatic system

Infrequently: leukopenia, eosinophilia, thrombocytopenia.

Frequency unknown: insufficiency of bone marrow hematopoiesis, pancytopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system disorders

Infrequently: the reaction of Jarish-Gerxheimer. As with the use of other antibiotics, in the treatment of borreliosis during the first days therapy, the development of the Yarisch-Gerxheimer reaction is possible. There are reports of the occurrence of one or more symptoms after a few weeks of treatment of borreliosis: skin rash, itching, fever, leukopenia, increased activity of "hepatic" enzymes, shortness of breath, discomfort in the joints. It should be borne in mind that to some extent, these manifestations are consistent with the symptoms of the underlying disease, over which the patient is receiving treatment.

Frequency unknown: anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock.

Disturbances from the nervous system

Infrequently: convulsions.

Frequency unknown: encephalopathy (eg, impaired consciousness, impaired motor activity), headache, dizziness.

Heart Disease

Frequency unknown: arrhythmias (due to rapid bolus administration through the central venous catheter).

Disorders from the gastro-intestinal tract

Infrequently: diarrhea.

Frequency unknown: nausea, vomiting, abdominal pain, pseudomembranous colitis.

Disorders from the liver and bile ducts

Infrequently: increased activity "hepatic" enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [ACT], lactate dehydrogenase [LDH], gamma-glutamyltransferase [gamma-GT], alkaline phosphatase [APF]) and / or concentration of bilirubin. These deviations in laboratory indicators (which can also be explained by the presence of infection), in rare cases exceed the upper border of the norm is 2 times and indicate to liver damage, manifested cholestasis and often leaking

is asymptomatic.

Frequency unknown: hepatitis (sometimes with jaundice).

Disturbances from the skin and subcutaneous tissue

Infrequently: rash, itching, hives.

Frequency unknown: multiform erythema, Stevens-Johnson, toxic

epidermal necrolysis, acute generalized exanthematous pustulosis.

Infringements from kidneys and urinary tract

Infrequently: reduced function kidney / increased concentration creatinine, especially when combined use with aminoglycosides.

Frequency unknown: acute renal insufficiency, interstitial nephritis.

General disorders and disorders in place of introduction

Often: pain at the injection site (with intramuscular injection).

Infrequently: fever, inflammatory reactions at the site of administration, including phlebitis / thrombophlebitis.

Frequency unknown: when intramuscular introduction, if in The quality of the solvent is lidocaine, possible development systemic reactions associated with lidocaine, especially in cases unintentional intravenous administration of the drug, injection into highly vascularized tissue or overdose.

Overdose:

There is a risk of developing reversible encephalopathy when using high doses of B-lactam antibiotics, including cefotaxime. There is no specific antidote.

Interaction:

Probenecid retards excretion and increases concentration

cephalosporins in the blood plasma. As with other cephalosporins, cefotaxime can enhance the nephrotoxic effect of drugs that havenephrotoxic effect (such as furosemide, aminoglycosides).

Compatibility guidelines: cefotaxime should not be mixed with other antibiotics (including aminoglycosides), as in one syringe, and in one infusion solution.

For infusions, the following solutions can be used (concentration of cefotaxime: 1 g / 250 ml): water for injection, 0.9% solution of sodium chloride, 5% dextrose solution, Ringer's solution lactate, Yonosteryl.

Special instructions:

Anaphylactic reactions

The appointment of cephalosporins requires the collection of an allergic anamnesis (allergic diathesis, hypersensitivity reactions to B-lactam antibiotics).

If the patient develops a hypersensitivity reaction, then the treatment should be stopped.

The use of cefotaxime is contraindicated in patients with a history of reaction

immediate type hypersensitivity to cephalosporins. In case of any doubt, the presence of a doctor at the first administration of the drug is necessary, in view of the possible anaphylactic reaction.

A cross-allergy between cephalosporins and penicillins is known, which occurs in

5-10% of cases. Anaphylactic reactions that develop in this situation can be serious or even fatal.

Patients who have a history of having an allergy to penicillins, the drug is used with extreme caution. Care should be taken to monitor the patient's condition with the first administration of the drug because of possible anaphylactic peaks.

In case of development of the first symptoms and signs of anaphylactic shock, the drug should be stopped immediately. The patient should remain in the "lying" position with raised legs. A slow intravenous injection of 0.1 mg (1 ml) of epinephrine solution (Epinephrine)

under the control of pulse and arterial pressure, and also in / in the introduction of plasma substitutes, human albumin or balanced electrolyte solutions; in the subsequent - in / in the introduction of glucocorticosteroids (for example, 250-1000 mg hydrocortisone), once or, if necessary, repeatedly. Supportive therapeutic measures should be carried out: artificial lung ventilation, inhalation with oxygen, administration of antihistamines

preparations.

Diseases caused by Clostridium difficile (eg, pseudomembranous colitis)

Diarrhea, especially severe and / or prolonged, developing during treatment or in the first weeks after the end of treatment with various antibiotics, especially a broad spectrum of action, may be a symptom of the disease,caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. The diagnosis of this rare, but possible and

fatal disease, is confirmed endoscopically and / or histologically. The most important method of confirming the diagnosis of pseudomembranous colitis is the detection of Clostridium difficile toxins in the stool. If you suspect a diagnosis of pseudomembranous colitis, cefotaxime should be discontinued immediately and the appropriate specific

antibiotic therapy (for example, oral administration of vancomycin or metronidazole). Preparations,

inhibiting peristalsis of the intestine, are contraindicated.

The use of lidocaine as a solvent

When using lidocaine as a solvent, the information provided in the section "Contraindications" should be taken into account.

The rate of administration

It is necessary to control the rate of administration of the drug (see section "Method of administration and dose").

Renal insufficiency

In renal failure, the dose should be adjusted depending on the creatinine clearance

(See section "Method of administration and dose").

Caution should be exercised while using cefotaxime and aminoglycosides.

Kidney function should be monitored in all cases of combined use

cefotaxime with aminoglycosides, other nephrotoxic drugs, in elderly patients

age or with renal insufficiency.

The sodium content

Patients requiring the intake of sodium limitations should be taken into account the sodium content of the sodium salt of cefotaxime (48.2 mg / g).

Hemorrhage disorders

During treatment, cefotaxime may develop leukopenia, neutropenia and more rarely

insufficiency of bone marrow hematopoiesis, pancytopenia and agranulocytosis.

With a duration of treatment more than 10 days should be monitored the number of blood cells. If the deviations from the norm of these blood parameters should be canceled drug.

Laboratory Tests

During therapy with cephalosporins, a positive Coombs test may occur.

It is recommended to use glucose oxidase methods for determining glucose concentration in

blood, due to the development of false positive results using nonspecific

reagents.

Effect on the ability to drive transp. cf. and fur:

In case of development of such a side effect as dizziness, the ability to

concentration and reactions.In this case, patients should refrain from driving

motor transport and work with mechanisms.

Form release / dosage:Powder for the preparation of solution for intravenous and intramuscular injection.

Packaging:For 1 g of the drug in a glass colorless bottle, corked with a rubber stopper and crimped with an aluminum cap, equipped with a plastic lid. 1 bottle with instructions for use in a cardboard box.

Storage conditions:Store at temperatures below + 25 ° C in a place protected from light and out of the reach of children.

Shelf life:2 years. After the expiration date, the drug can not be used.

Terms of leave from pharmacies:On prescription

Registration number:P N008945

Date of registration:05.09.2011

The owner of the registration certificate:Aventis Pharma LimitedAventis Pharma Limited United Kingdom

Manufacturer: & nbsp

PATHEON UK, Ltd. United Kingdom

Representation: & nbspPharm Company Sotex CJSC Pharm Company Sotex CJSC Russia

Information update date: & nbsp02.11.2015

Illustrated instructions

Instructions

Claforan® (Claforan®)