Cefotaxime,.fl 1 g + 5 ml 1 amp.

Pharmacotherapeutic group

Cephalosporin antibiotic

ATX code: J01DD01

Pharmacodynamics

A semisynthetic antibiotic of the group of III generation cephalosporins. Cefotaxime acts bactericidally by disrupting the synthesis of the bacterial wall. It is also resistant to the action of most β-lactamases.

The following bacteria are usually sensitive to cefotaxime: 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 nonproducing strains); Morganella morgcinii; Neisseria gonorrhoeae (including penicillinase-producing and nonproducing strains); Neisseria meningitidis; Propionibacterium spp.Proteus mirabilis; Proteus vulgaris; Providencia spp.; Streptococcus spp. (including Streptococcus pneumoniae); Salmonella spp.; Serratia spp*; Shigella spp; Veillonella spp.*;Yersinia spp.*; Pseudomonas spp. (except Pseudomonas aeruginosa, Pseudomonas cepacia).

*Sensitivity depends on epidemiological data and on the level of resistance in each specific country.

The following are resistant to cefotaxime: 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

Absorption and distribution

In adults, 5 minutes after a single intravenous (IV) injection of 1 g of cefotaxime, the maximum concentration (Cmax) in blood plasma is 100 mcg/ml. After intramuscular (i/m) injection of cefotaxime at the same dose Cmax in plasma is reached after 0.5 h and is 20 to 30 mcg/ml. Bioavailability of cefotaxime when administered intravenously is 100%, when administered intravenously – 90-95%.

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

Metabolism

Metabolized in the liver with the formation of the active metabolite desacetylcephotaxime (Ml), which has antibacterial activity, and inactive metabolites (M2, M3).

Excretion

About 90% of the administered dose is excreted by the kidneys: 50% – unchanged, about 15-25% as the metabolite deacetylcephotaxime and 15-30% as inactive metabolites (M2-M3). 10% of the administered dose is excreted by the intestine. The half-life (T1/2) of cefotaxime is 1 h when administered by IV and 1-1.5 h when administered by IV/m.

In elderly patients over 80 years old the T1/2 of cefotaxime is increased to 2.5 h. The volume of distribution (Vd) does not change compared to young healthy volunteers.

In adults with impaired renal function, Vd is unchanged and T1/2 does not exceed 2.5 h, even in the last stages of renal failure.

In children the plasma concentration of cefotaxime and Vd are similar to those in adults receiving the same dose of the drug in mg kg weight. T1/2 of cefotaxime is 0.75 to 1.5 h.

In newborns and prematurely born children the plasma concentration of cefotaxime and Vd are similar to those in children. Mean T1/2 of cefotaxime is 1.4 to 6.4 h.

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;

– intraabdominal infections (including peritonitis);

– meningitis (except listeria) and other central nervous system (CNS) infections;

– skin and soft tissue infections;

– bone and joint infections.

The prevention of infections after surgical operations on the gastrointestinal tract (GIT), urological, obstetric and gynecological operations.

Active ingredient

Composition

1 vial contains:

The active ingredient

Cefotaxime sodium (in terms of cefotaxime) – 1 g.

How to take, the dosage

Intramuscularly (i.m.) or intravenously (i.v.).

The dose, route and frequency of administration should be determined by the severity of the infection, the sensitivity of the pathogen and the patient’s condition. Treatment can be started before the results of the sensitivity test are available.

Adults and children over 12 years of age and weighing 50 kg or more:

For mild to moderate infections, 1 g every 12 hours. The dose may vary depending on the severity of the infection, the sensitivity of the pathogen and the patient’s condition;

– In severe infections, the dose may be increased to 12 g per day, divided into 3 or 4 injections;

– In infections caused by Pseudomonas spp. the daily dose should be more than 6 g.

Children under 12 years of age and with a body weight under 50 kg:

The usual dose is 100-150 mg/kg/day, divided into 2 to 4 injections;

In very severe infections, the dose may be increased to 200 mg kg/day.

Newborns:

– dose of 50 mg/kg/day. divided into 2-4 injections;

– for severe infections, dose of 150-200 mg/kg/day, divided into 2-4 injections.

In gonorrhea:

1 g once in/v or i/m.

For prophylaxis before surgery (30 to 90 minutes before surgery), administer 1 g w/v or w/m.

In case of caesarean section at the time of application of clamps on the umbilical vein, 1 g of the drug is administered IV, then after b 12 hours 1 g is administered again IV or IM.

In case of renal failure: in cases where creatinine clearance is less than 10 ml/min, the dose should be reduced. After the initial single dose, the daily dose should be halved without changing the frequency of administration, i.e. instead of 1 g every 12 hours, 0.5 g every 12 hours. instead of 1 g every 8 hours, 0.5 g every 8 hours, instead of 2 g every 8 hours, 1 g every 8 hours, etc. Further dose adjustments may be required depending on the course of the infection and the patient’s general condition.

Patients on hemodialysis are prescribed 1-2 g per day depending on the severity of the infection. On the day of hemodialysis, cefotaxime should be administered after the end of the hemodialysis session, since cefotaxime is removed during hemodialysis. Patients on peritoneal dialysis are prescribed 1-2 g per day depending on the severity of the infection. Cefotaxime is not removed during peritoneal dialysis.

Rules for preparation of solutions: for intravenous injection, water for injection is used as solvent (0.5 g diluted in 2 ml of solvent, 1 g in 4 ml, 2 g in 10 ml); during intravenous injection the solution should be injected within 3 to 5 minutes. For intravenous infusion 0.9% sodium chloride solution or 5% dextrose solution (1-2 g diluted in 40-100 ml of solvent) is used as a solvent. Ringer’s lactate solution can also be used. Infusion duration is 20-60 minutes. For intramuscular injection, water for injection or 1% lidocaine solution is used (for 0.5 g drug dose – 2 ml of solvent, for 1 g dose – 4 ml, for 2 g dose – 10 ml).

Interaction

Probenecid delays excretion and increases plasma concentrations of cephalosporins.

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

Prompts for compatibility: cefotaxime should not be mixed with other antibiotics (including aminoglycosides), both in the same syringe and in the same infusion solution.

The following solutions may be used for infusion (cefotaxime concentration 1 g/250 ml): water for injection, 0.9% sodium chloride solution, 5% dextrose solution, Ringer’s lactate solution, Jonosteril.

Special Instructions

Anaphylactic reactions

An allergic history (allergic diathesis, hypersensitivity reactions to β-lactam antibiotics) is required before using cephalosporins. If a patient develops a hypersensitivity reaction, treatment must be discontinued.

The use of cefotaxime is contraindicated in patients with a history of immediate hypersensitivity reactions to cephalosporins. If there is any doubt, a physician must be present the first time the drug is administered because of a possible anaphylactic reaction.

Cross-allergy between cephalosporins and penicillins is known to occur in 5-10% of cases. Anaphylactic reactions developing in this situation can be serious or even fatal.

In patients with a history of allergy to penicillins, the drug is used with extreme caution. The patient’s state should be carefully monitored during the first administration of the drug due to possible anaphylactic reaction. If the first symptoms and signs of anaphylactic shock develop, the drug administration should be stopped immediately. The patient should remain in the supine position with elevated legs. Slow intravenous injection of 0.1 mg (1 ml) of epinephrine (adrenaline) solution under monitoring of heart rate and blood pressure is indicated, as well as intravenous injection of plasma substitutes, human albumin or balanced electrolyte solutions; subsequently, intravenous injection of glucocorticosteroids (e.g., 250-1000 mg of hydrocortisone), once or repeatedly if necessary. Supportive therapeutic measures should be carried out: artificial lung ventilation, oxygen inhalation, administration of antihistamines.

Diseases caused by Clostridium difficile (e.g., pseudomembranous colitis)

Diarrhea, especially severe and/or prolonged diarrhea that develops during treatment or in the first weeks after treatment with various antibiotics, especially 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 Clostridium difficile toxins in feces. If the diagnosis of pseudomembranous colitis is suspected, cefotaxime should be stopped immediately and appropriate specific antibiotic therapy (e.g. oral vancomycin or metronidazole) started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

Encephalopathy

The use of beta-lactam antibiotics, including cefotaxime, increases the risk of encephalopathy (which may manifest as seizures, confusion, impaired consciousness, movement disorders), especially in case of overdose or renal failure.

The use of lidocaine as a solvent

When using lidocaine as a solvent, the information under “Contraindications” must be considered.

The rate of administration

The rate of administration must be controlled (see section “Administration and Doses”).

Renal failure

The dose should be adjusted according to creatinine clearance if there is renal failure (see section “Administration and Doses”).

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

Hematopoietic disorders

When treating with cefotaxime leukopenia, neutropenia and more rarely bone marrow hematopoiesis, pancytopenia and agranulocytosis may develop. During the treatment course of more than 10 days the number of blood cells should be monitored. In case of deviations from normal blood counts the drug should be discontinued.

The sodium content of cefotaxime sodium salt (48.2 mg/g) should be taken into account in patients who require sodium restriction.

Laboratory tests

A positive Coombs test may occur during therapy with cephalosporins. The use of glucose oxidase methods of determining blood glucose concentration is recommended due to the development of false-positive results when using non-specific reagents.

In case of adverse reactions such as dizziness and encephalopathy (which may be manifested by seizures, confusion, impaired consciousness, movement disorders), patients should refrain from driving and operating machinery.

Contraindications

Hypersensitivity to cefotaxime, other cephalosporins.

For forms containing lidocaine as a solvent:

– hypersensitivity to lidocaine or another amide-type local anesthetic;

– intracardiac blockages without an established pacemaker;

– severe heart failure;

– intravenous administration;

– children under 2.5 years of age (intramuscular administration).

With caution

In patients with a history of allergy to penicillins (risk of cross-allergic reactions); concomitant use with aminoglycosides; in renal failure.

Side effects

Classification of adverse reactions according to the frequency of development, according to the recommendations of the World Health Organization: Very common (>10%); common (>1% and <10%); infrequent (>0.1% and <1%); rare (>0.01% and <0.1%); very rare (<0.01%); frequency unknown (based on available data, the frequency of adverse effects cannot be estimated).

Infectious and parasitic diseases

Frequency unknown: superinfections. The use of cefotaxime, as well as other antibiotics, especially long-term, may lead to an overgrowth of insensitive microorganisms. The patient’s condition should be monitored regularly. If the development of superinfection occurs during therapy with cefotaxime, appropriate measures should be taken.

Blood and lymphatic system disorders

Infrequent: leukopenia, eosinophilia, thrombocytopenia.

Prevalence unknown: insufficiency of medullary hematopoiesis, pancytopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system disorders

Infrequent: Jarisch-Herxheimer reaction. As with the use of other antibiotics, a Jarisch-Herxheimer reaction may develop during the first days of therapy when treating borreliosis. There are reports of the occurrence of one or more symptoms after a few weeks of borreliosis treatment: skin rash, itching, fever, leukopenia, increased liver enzyme activity, difficulty in breathing, discomfort in the joints. Note that to some degree these manifestations are consistent with the symptoms of the underlying disease for which the patient is receiving treatment.

Prevalence unknown: anaphylactic reactions, angioedema, bronchospasm,

anaphylactic shock.

Nervous system disorders

Infrequent: seizures.

Prevalence unknown: encephalopathy (which may manifest as seizures, confusion, impaired consciousness, impaired motor activity), headache, dizziness.

Cardiac disorders

Prevalence unknown: arrhythmias (due to rapid bolus injection through a central venous catheter).

Gastrointestinal disorders

Infrequent: diarrhea.

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

Liver and biliary tract disorders

Infrequent: Increased activity of “hepatic” enzymes (alanine aminotransferase (ALT), aspartagaminotransferase (ACT), lactate dehydrogenase (LDH), gamma glutamyltransferase (GGT), alkaline phosphatase (ALP) and or bilirubin concentration. These abnormal laboratory values (which can also be explained by the presence of infection), rarely exceed the upper limit of the norm by a factor of 2 and indicate liver damage manifested by cholestasis and are often asymptomatic.

Prevalence unknown: hepatitis (sometimes with jaundice).

Skin and subcutaneous tissue disorders

Infrequent: rash, itching, urticaria.

Prevalence unknown: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis.

Renal and urinary tract disorders

Infrequent: decreased renal function/increased concentration of creatinine, especially when combined with aminoglycosides.

Often unknown: acute renal failure, interstitial nephritis.

General disorders and disorders at the site of injection

Often: pain at the site of injection (when administered intramuscularly).

Infrequent: fever, inflammatory reactions at the injection site including phlebitis/thrombophlebitis.

Prevalence unknown: In intramuscular injection, if lidocaine is used as a solvent, systemic reactions associated with lidocaine may develop, especially in cases of unintentional intravenous administration of the drug, injection into highly vascularized tissues or in overdose.

Overdose

Pregnancy use

Pregnancy

Cefotaxime penetrates the placental barrier. Studies conducted on animals have not revealed teratogenic or fetotoxic effects of cefotaxime. However, the safety of cefotaxime in human pregnancy has not been established, so the use of cefotaxime is contraindicated in pregnancy.

Breast-feeding period

Cefotaxime penetrates into the breast milk; therefore, if it is necessary to use the drug, breast-feeding should be stopped.

Similarities