Cefotaxime powder solution 1g vials, 1pc – Belmedpreparaty

Composition

Per bottle:  active substance:  cefotaxime (in the form of cefotaxime sodium salt) – 1000 mg

Pharmacological action

Pharmacotherapeutic group: Antibiotic-cephalosporin

ATX Code: J01DD01

Pharmacodynamics :

Cephalosporin antibiotic of the third generation for parenteral use. It acts bactericidal by disrupting the synthesis of mucopeptide of the cell wall of microorganisms. It has a wide spectrum of action.

Usually sensitive to cefotaxime:  Aeromonashydrophila Bacillussubtilis Bordetellapertussis Borreliaburgdorferi Moraxellacatarrhalis Citrobacterdiversus* Citrobacterfreundii* Clostridiumperfringens Corynebacteriumdiphtheriae Escherichiacoli Enterobacterspp. * Erysipelothrixinsidiosa Eubacteriumspp. Haemophilus Spp. (penicillinase-producing and non-producing strains, including ampicillin-resistant ones) Klebsiellapneumoniae Klebsiellaoxytoca Staphylococcusspp. (methicillin-sensitive including penicillinase-producing and non-producing strains) Morganellamorganii Neisseriagonorrhoea (including penicillinase-producing and non-producing strains) Neisseriameningitidis Propionibacteriumspp. Proteusmirabilis Proteusvulgaris Providenciaspp. Streptococcusspp. (including Streptococcuspneumoniae) Salmonellaspp. Serraliaspp. * Shigellaspp. Veillonellaspp. Yersiniaspp. * Pseudomonasspp. (except Pseu­domonasaeruginosa Pseudomonascepacia).

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

They are resistant to cefotaxime:  Acinetobacterbaumanii Bacteroidesfragilis Clostridiumdifficile Enterococcusspp. gram-negative anaerobes Listeriamonocytogenes Staphylococcusspp. (methicillin-resistant strains) Pseudomonas aeruginosa Pseudomonas cepacia Stenotrophomonas maltophilia.

Pharmacokinetics:

In adults,5 minutes after a single intravenous (iv) use of 1 g of cefotaxime, the maximum concentration (Cmax) in blood plasma is 100 mcg/ml. After intramuscular (iv) use of cefotaxime at the same dose, Cmax in blood plasma is reached in 05 hours and ranges from 20 to 30 mcg / ml. The bioavailability of cefotaxime with intravenous use is 100% with intravenous use-90-95%.

The half-life (T 1/2) of cefotaxime is 1 hour with intravenous use and 1-15 hours with intramuscular use.

Binding to plasma proteins (mainly albumins) is on average 25-40%. It is metabolized in the liver to form the active metabolite of deacetylcefotaxime (M1), which has antibacterial activity, and inactive metabolites (M2m3). About 90% of the administered dose is excreted by the kidneys: 50% – unchanged, about 15-25% in the form of the deacetylcefotaxime metabolite and 15-30% in the form of inactive metabolites (M2 + M3).10% of the administered dose is excreted by the intestine.

In elderly patients over 80 years of age, the T 1/2 of cefotaxime increases to 25 hours. The volume of distribution (Vd) does not change in comparison with young healthy volunteers.

In adults with impaired renal function, Vd does not change and T 1/2 does not exceed 25 hours, even in the last stages of renal failure.

In children, the concentration of cefotaxime in blood plasma and Vd are similar to those in adults receiving the same dose of the drug in mg/kg of body weight. The T 1/2 of cefotaxime ranges from 0.75 to 15 hours.

In newborns and prematurely born children, the concentration of cefotaxime in blood plasma and Vd are similar to those in children. The average T 1/2 of cefotaxime is 14 to 64 hours.

Indications

Cefotaxime is intended for the treatment of infections caused by microorganisms sensitive to the drug:

– respiratory tract infections;

– urinary tract infections;

– septicemia bacteremia;

– endocarditis;

– intra-abdominal infections (including peritonitis);

– meningitis (excluding listeriosis) and other infections of the central nervous system;

– skin and soft tissue infections;

– bone and joint infections.

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

Use during pregnancy and lactation

Pregnancy

Cefotaxime penetrates the placental barrier. Animal studies have not shown any teratogenic or fetotoxic effects of the drug. However, the safety of using cefotaxime during pregnancy in humans has not been established, so the drug should not be used during pregnancy.

The period of breastfeeding

Cefotaxime penetrates into breast milk, so if it is necessary to prescribe the drug, breastfeeding should be interrupted.

Contraindications

-Hypersensitivity to cefotaxime and other cephalosporins.

– For forms containing lidocaine as a solvent:

– hypersensitivity to lidocaine or other local anaesthetic of the amide type;

– intracardiac blockages without an established pacemaker;

– severe heart failure;

– intravenous use;

– children under 25 years of age (intramuscular use).

With caution:

In patients with a history of allergy to penicillins (risk of cross-allergic reactions);

with simultaneous use with aminoglycosides;

with renal failure.

Side effects

Classification of adverse reactions by frequency according to the World Health Organization guidelines: very common (≥10%); common (≥1% and <10%); uncommon (≥01% and <1%); rare (≥001% and <01%); very rare (

Infectious and parasitic diseases: frequency unknown:  superinfections. As with other antibiotics, especially prolonged use of cefotaxime can lead to excessive growth of insensitive microorganisms. The patient’s condition should be monitored regularly. If superinfection occurs during cefotaxime therapy, appropriate measures should be taken.

Blood and lymphatic system disorders: infrequent:  leukopenia eosinophilia thrombocytopenia. Frequency unknown:  insufficiency of bone marrow hematopoiesis pancytopenia neutropenia agranulocytosis hemolytic anemia.

Immune system disorders: infrequent:  the Yarish-Gerksheimer reaction. As with the use of other antibiotics in the treatment of borreliosis during the first days of therapy, a Jarisch-Herxheimer reaction may develop. There are reports of one or more symptoms occurring after a few weeks of treatment for borreliosis: skin rash pruritus fever leukopenia increased activity of “liver” enzymes difficulty breathing joint discomfort. It should be borne in mind that to some extent these manifestations are consistent with the symptoms of the underlying disease for which the patient is receiving treatment. Frequency unknown:  anaphylactic reactions angioedema bronchospasm anaphylactic shock.

Nervous system disorders: infrequent:  convulsions. Frequency unknown:  encephalopathy (e. g. impaired consciousness motor activity disorders) headache dizziness.

Cardiac disorders: frequency unknown:  arrhythmias (due to rapid bolus insertion through a central venous catheter).

Gastrointestinal disorders: infrequent:  diarrhea. Frequency unknown:  nausea vomiting abdominal pain pseudomembranous colitis.

Liver and biliary tract disorders: infrequent:  increased activity of “liver” enzymes (alanine aminotransferase (ALT) aspartate aminotransferase (ACT) lactate dehydrogenase (LDH) gamma-glutamyltransferase (gamma-GT) alkaline phosphatase (ALP)) and/or bilirubin concentration. These deviations in laboratory parameters (which can also be explained by the presence of infection) in rare cases exceed the upper limit of normal by 2 times and indicate liver damage manifested by cholestasis and often asymptomatic. Frequency unknown:  hepatitis (sometimes with jaundice).

Skin and subcutaneous tissue disorders: infrequent:  rash pruritus urticaria. Frequency unknown:  erythema multiforme Stevens-Johnson syndrome toxic epidermal necrolysis acute generalized exanthematous pustulosis.

Renal and urinary tract disorders: infrequent:  decreased renal function/ increased creatinine, especially when co-administered with aminoglycosides. Frequency unknown:  acute renal failure interstitial nephritis.

General disorders and disorders at the injection site: often:  pain at the injection site (when administered intramuscularly). Infrequently:  fever inflammatory reactions at the injection site including phlebitis / thrombophlebitis. Frequency unknown:  when administered intramuscularly if lidocaine is used as a solvent it is possible to develop systemic reactions associated with lidocaine especially in cases of unintentional intravenous use of the drug injections into highly vascularized tissues or overdose.

Interaction

Probenecid delays excretion and increases the concentration of cephalosporins in blood plasma.

As with other cephalosporins, cefotaxime may enhance the nephrotoxic effect of drugs with nephrotoxic effects (such as furosemide aminoglycosides).

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

For infusions, the following solutions can be used (cefotaxime concentration 1 g / 250 ml): water for injection 09% sodium chloride solution 5% dextrose solution Ringer’s solution lactate Ionosteryl.

How to take, course of use and dosage

Either intravenously or intramuscularly. The dose method and frequency of use should be determined by the severity of the infection the sensitivity of the pathogen and the patient’s condition. Treatment can be initiated before receiving the results of a sensitivity test.

Adults and children over 12 years of age and weighing 50 kg or more: for mild and moderate infections-1000 mg every 12 hours. The dose may vary depending on the severity of the infection, the sensitivity of the pathogen and the patient’s condition. For severe infections, the dose can be increased to 12,000 mg per day divided into 3 or 4 injections. For infections caused by Pseudomonasspp. the daily dose should be more than 6000 mg. Children under 12 years of age and weighing up to 50 kg: the usual dose is 100-150 mg / kg / day divided into 2-4 injections. For very severe infections, the dose can be increased to 200 mg / kg / day. Newborns: 50 mg / kg / day divided into 2-4 injections. For severe infections – a dose of 150-200 mg / kg / day divided into 2-4 injections.

For gonorrhea: 1000 mg once intravenously or intramuscularly.

In order to prevent infections before surgery (from 30 to 90 minutes before the operation),1000 mg is administered intramuscularly or intravenously.

When performing a caesarean section,1000 mg of the drug is administered intravenously at the time of applying clamps to the umbilical vein, then 1000 mg is re-administered intravenously or intramuscularly after 6 and 12 hours.

In patients with renal insufficiency: in cases where the creatinine clearance is less than 10 ml/min, the dose should be reduced. After use of the initial single dose, the daily dose should be halved without changing the frequency of use, i. e. instead of 1000 mg every 12 hours-500 mg every 12 hours instead of 1000 mg every 8 hours-500 mg every 8 hours instead of 2000 mg every 8 hours-1000 mg every 8 hours, etc.

Rules for preparing solutions: for intravenous injection, water for injection is used as a solvent (500 mg is diluted in 2 ml of solvent,1000 mg-in 4 ml); for intravenous injection, the solution should be administered within 3 to 5 minutes. For intravenous infusion, a 09% NaCl solution or 5% dextrose solution is used as a solvent (1-2 g is diluted in 40-100 ml of solvent). Ringer’s lactate solution can also be used. The duration of the infusion is 20-60 minutes. For intramuscular use, use water for injection or 1% lidocaine solution (500 mg diluted in 2 ml of solvent 1000 mg-in 4 ml).

Overdose

There is a risk of developing reversible encephalopathy with the use of beta-lactam antibiotics including cefotaxime, especially in cases of overdose or impaired renal function. There is no specific antidote. Cefotaxime can be removed by hemodialysis and is not removed by peritoneal dialysis.

Special instructions

Anaphylactic reactions

use of cephalosporins requires the collection of an allergic history (allergic diathesis of hypersensitivity reactions to beta-lactam antibiotics).

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

The use of cefotaxime is contraindicated in patients with a history of immediate hypersensitivity reactions to cephalosporins. In case of any doubts, the presence of a doctor at the first use of the drug is mandatory due to a possible anaphylactic reaction.

There is a known cross-allergy between cephalosporins and penicillins that occurs in 5-10% of cases. Anaphylactic reactions that develop in this situation can be serious or even fatal.

In patients with a history of penicillin allergy, the drug is used with extreme caution. The patient’s condition should be carefully monitored at the first use of the drug due to a possible anaphylactic reaction.

If the first symptoms and signs of anaphylactic shock develop, the drug should be discontinued immediately. The patient should remain in the “lying” position with the legs raised. Slow intravenous use of 01 mg (1 ml) of epinephrine (epinephrine) solution under pulse and blood pressure control is indicated, as well as intravenous use of human albumin plasma substitutes or balanced electrolyte solutions; subsequently, intravenous use of glucocorticosteroids (for example,250-1000 mg of hydrocortisone) once or if necessary repeatedly.

Supportive therapeutic measures should be taken: artificial ventilation, oxygen inhalation, use of antihistamines.

Diseases caused by Clostridium Difficile (e. g. pseudomembranous colitis)

Diarrhea especially severe and / or prolonged that develops during treatment or in the first weeks after the end of treatment with various particularly broad-spectrum antibiotics may be a symptom of a disease caused by Clostridium Difficile, the most severe form of which is pseudomembranous colitis. The diagnosis of this rare but possibly fatal disease is confirmed endoscopically and / or histologically. The most important method of confirming the diagnosis of pseudomembranous colitis is the detection of toxins Clostridium Difficile in the stool. If a diagnosis of pseudomembranous colitis is suspected, cefotaxime should be discontinued immediately and appropriate specific antibiotic therapy (for example, oral vancomycin or metronidazole) should be initiated immediately. Drugs that inhibit intestinal motility are contraindicated.

Encephalopathy

When using beta-lactam antibiotics including cefotaxime, the risk of developing encephalopathy (which can manifest as seizures, confusion, impaired consciousness, motor disorders) increases, especially in the case of overdose or kidney failure.

Application of lidocaine as a solvent

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

Introduction rate

The rate of use of the drug should be monitored (See the section “Dosage and use”).

Kidney failure

In patients with renal insufficiency, the dose should be adjusted depending on creatinine clearance (See section “Dosage and use”).

Caution should be exercised when concomitantly using cefotaxime and aminoglycosides. Renal function should be monitored in all cases of combined use of cefotaxime with aminoglycosides and other nephrotoxic drugs in elderly patients or with renal insufficiency.

Sodium content

In patients requiring restricted sodium intake, the sodium content of cefotaxime sodium salt (482 mg/g) should be taken into account.

Hematopoietic disorders

During treatment with cefotaxime, leukopenia neutropenia and, more rarely, bone marrow hematopoiesis failure pancytopenia and agranulocytosis may develop.

If the course of treatment lasts more than 10 days, the number of formed blood elements should be monitored. If these blood parameters deviate from the norm, the drug should be discontinued.

Laboratory tests

During cephalosporin therapy, a positive Coombs test may occur. It is recommended to use glucose-oxidase methods for determining the concentration of glucose in the blood due to the development of false positive results when using non-specific reagents.

Influence on the ability to drive vehicles and mechanisms:

In the event of such adverse reactions as dizziness and encephalopathy (which may be manifested by convulsions confusion disorders of consciousness motor disorders), patients should refrain from driving vehicles and working with mechanisms.

Form of production

Powder for solution preparation for intravenous and intramuscular use

Storage conditions

Store in a dark place at a temperature not exceeding 25°C.

Keep out of the reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Cefotaxime

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion