Instructions Cefotaxime powder for solution for injection 1 g bottle No. 10
Composition
active ingredient: cefotaxime;
1 vial contains cefotaxime sodium salt sterile equivalent to cefotaxime 1 g.
Dosage form
Powder for solution for injection.
Main physicochemical properties: white or slightly yellow powder. Hygroscopic.
Pharmacotherapeutic group
Antimicrobials for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. ATX code J01D D01.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Cefotaxime is a broad-spectrum third-generation cephalosporin antibiotic for parenteral administration. Cefotaxime inhibits enzymes responsible for bacterial cell wall synthesis. This leads to bacterial cell lysis.
Resistance mechanisms
Bacterial resistance to cefotaxime may result from one or more of the following mechanisms:
hydrolysis by beta-lactamase. Cefotaxime can be hydrolyzed by many so-called “extended spectrum” beta-lactamases. It is also hydrolyzed by chromosomally encoded (Amp-C type) beta-lactamases; resistance based on impermeability; mechanism of expression of efflux pumps.
Several of these mechanisms can exist simultaneously in a single bacterium.
Cefotaxime-resistant bacteria may exhibit cross-resistance to varying degrees to other beta-lactam antibiotics. Cefotaxime-resistant Gram-negative bacteria exhibit cross-resistance to other broad-spectrum third-generation cephalosporins (ceftazidime, ceftriaxone).
Limit values
The minimum inhibitory concentration (MIC) breakpoints for cefotaxime recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which distinguish susceptible from resistant microorganisms, are given in the table below.
Clinical breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cefotaxime:
| Pathogenic microorganism | Sensitive | Resistant |
| Enterobacteriaceae | ≤ 1 mg/l | > 2 m/l |
| S. pneumoniae | ≤ 0.5 mg/l | > 2 mg/l |
| Other Streptococci | ≤ 0.5 mg/l | > 0.5 mg/l |
| H. influenza | ≤ 0.12 mg/l | > 0.12 mg/l |
| M. cattarhalis | ≤ 1 mg/l | > 2 mg/l |
| N. gonorrhea | ≤ 0.12 mg/l | > 0.12 mg/l |
| N. meningitidis | ≤ 0.12 mg/l | > 0.12 mg/l |
| Limit values not related to the bacterial species | ≤ 1 mg/l | > 2 mg/l |
The sensitivity of Staphylococcus to cephalosporins stems from their sensitivity to methicillin. The sensitivity of streptococci (Streptococcus) groups A, B, C, G stems from their sensitivity to benzylpenicillin. | | |
Spectrum of antibacterial action
The prevalence of resistance of individual species may vary, depending on the region and time. When treating serious infections, it is advisable to take into account local information on resistance. If necessary, specialist advice should be sought when the local prevalence of resistance is such that the benefit of use is questionable.
| Typically susceptible species of microorganisms |
| Aerobic Gram-positive bacteria |
| Methicillin-susceptible Staphylococcus aureus |
| Methicillin-sensitive coagulase-negative staphylococci |
| Methicillin-susceptible Staphylococcus epidermis |
| Methicillin-susceptible Staphylococcus haemolyticus |
| Group A streptococci (including Streptococcus pyogenes) |
| Group B streptococci |
| Streptococcus pneumoniae |
| Streptococcus viridans group |
| Aerobic Gram-negative bacteria |
| Citrobacter spp. (excluding Citrobacter freundii) |
| Escherichia coli |
| Haemophilus influenzae |
| Moraxella catarrhalis |
| Neisseria gonorrhoeae |
| Neisseria meningitidis |
| Klebsiella spp. |
| Proteus mirabilis |
| Serratia spp. |
| Yersinia enterocolitica |
| Other types of microorganisms |
| Borrelia spp. |
| Types of microorganisms that can acquire resistance |
| Bacteroides fragilis |
| Enterobacter spp. |
| Aerobic Gram-positive bacteria |
| Methicillin-resistant Staphylococcus aureus |
| Methicillin-resistant coagulase-negative staphylococci |
| Aerobic Gram-negative bacteria |
| Acinetobacter spp. |
| Citrobacter freundii |
| Morganella morganii |
| Providencia spp. |
| Pseudomonas aeruginosa |
| Stenotrophomonas maltophilia |
| Inherently resistant microorganisms |
| Aerobic Gram-positive bacteria |
| Enterococcus spp. |
| Other types of microorganisms |
| Chlamydia spp. |
| Legionella pneumophila |
| Listeria spp. |
| Mycoplasma spp. |
| Treponema pallidum |
Pharmacokinetics
After intramuscular administration of cefotaxime, its maximum serum concentration (approximately 20 mg/l after administration of 1 g) was reached after 30 minutes.
Distribution
Cefotaxime rapidly penetrates into tissues, crosses the placental barrier and reaches high concentrations in fetal tissues (up to 6 mg/kg). It is found in breast milk only in low quantities (concentration in breast milk 0.4 mg/l after administration of 2 g).
In case of inflammation of the membranes of the brain or spinal cord, cefotaxime and desacetylcefotaxime penetrate into the cerebrospinal fluid and reach therapeutically effective concentrations of the substance there (for example, in infections caused by gram-negative bacteria and pneumococci).
The apparent volume of distribution is 21–37 L. It is approximately 25–40% bound to plasma proteins.
Metabolism
Cefotaxime is extensively metabolized in humans. Approximately 15–25% of a parenterally administered dose is excreted as O-desacetylcefotaxime. The metabolite has antibacterial activity.
In addition to desacetylcefotaxime, two inactive metabolites (lactones) are formed. The lactone is formed from desacetylcefotaxime as a short-lived intermediate that is soon undetectable in urine or plasma because it is rapidly converted to the stereoisomers of the lactone with an open ring structure (β-lactam ring). These are also excreted in the urine.
Excretion
Cefotaxime and desacetylcefotaxime are excreted primarily by the kidneys. A small percentage (about 2%) is excreted in the bile. In urine collected over 6 hours, 40–60% of the dose was recovered as unchanged drug and approximately 20% as desacetylcefotaxime. After intravenous administration of radiolabeled cefotaxime, more than 80% was recovered in the urine, of which 50–60% was recovered as unchanged drug and the remainder as 3 metabolites.
The total clearance of cefotaxime is 240–390 ml/min, and the renal clearance is 130–150 ml/min.
The serum half-lives of cefotaxime and the active metabolite are 50–80 and 125 minutes, respectively. In elderly patients (> 80 years), the half-lives for cefotaxime and the active metabolite were 120–150 minutes and 5 hours, respectively.
In cases of severe renal impairment (creatinine clearance 3–10 ml/min), the half-life of cefotaxime may be prolonged to 2.5–10 hours.
Cefotaxime accumulates under these conditions only to a minor extent, unlike the active and inactive metabolites.
Both cefotaxime and desacetylcefotaxime are largely removed from the blood by hemodialysis.
Indication
Use for the treatment of the following serious infections that are caused or are highly likely to be caused by microorganisms susceptible to cefotaxime:
Bacterial pneumonia (cefotaxime is not effective against the bacteria that cause atypical pneumonia or against various other bacterial strains that can cause atypical pneumonia, including P. aeruginosa).
Complicated kidney and upper urinary tract infections.
Serious skin and soft tissue infections.
Genital infections caused by gonococci, especially when the use of penicillin has proven ineffective or is not appropriate.
Intra-abdominal infections (including peritonitis): In the treatment of intra-abdominal infections, cefotaxime should be used in combination with an antibiotic that is active against anaerobic microorganisms.
Acute bacterial meningitis (especially caused by H. Influenzae, N. Meningitis, S. pneumoniae, E. coli, Klebsiella spp.).
Lyme disease, or tick-borne borreliosis (especially stages II and III).
Bacteremias associated or suspected to be associated with one of the listed infections (if the infection is caused by Gram-negative bacteria, it should be combined with another appropriate antibiotic).
Endocarditis (if the infection is caused by gram-negative bacteria, it should be combined with another appropriate antibiotic).
For perioperative prevention of infectious complications (before/after surgical operations, in particular on the colon and rectum (colorectal surgery), on the gastrointestinal tract, prostate gland, in the genitourinary system, obstetric and gynecological operations in patients with a high risk of postoperative infections).
Official recommendations on the proper use of antibacterial agents should be taken into account.
Contraindication
Hypersensitivity to cephalosporin antibiotics and other β-lactam antibiotics.
Contraindications for the use of solutions containing lidocaine:
hypersensitivity to lidocaine or other amide-type local anesthetics; atrioventricular blocks without an established pacemaker; severe heart failure; intravenous administration; children under 1 year of age (intramuscular administration).
Incompatibility. The drug solution is incompatible with aminoglycoside solutions in the same syringe or dropper. For dilution, use the solutions specified in the section "Method of administration and dosage", "Interaction with other medicinal products and other types of interactions".
Interaction with other medicinal products and other types of interactions
Uricosuric drugs
This increases cefotaxime exposure by approximately two-fold and reduces renal clearance by approximately 50% at therapeutic doses. Given the wide therapeutic range of cefotaxime, no dosage adjustment is necessary for patients with normal renal function. Dosage adjustment may be necessary for patients with impaired renal function.
Aminoglycoside antibiotics and diuretics
As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effects of nephrotoxic drugs such as aminoglycosides and potent diuretics (such as furosemide). Renal function should be monitored in these patients.
Cefotaxime should not be combined with bacteriostatic antibiotics (e.g. tetracycline, erythromycin and chloramphenicol) as an antagonistic effect may occur.
The following solutions can be used for infusions: water for injection, 0.9% sodium chloride solution, 5% dextrose, Ringer's solution.
Application features
As with other antibiotics, the use of cefotaxime, especially long-term use, may result in overgrowth of non-susceptible organisms. It is important to monitor the patient regularly. If superinfection occurs during treatment, appropriate measures should be taken.
In case of prolonged use, liver and kidney function should be monitored.
Anaphylactic reactions
Serious, including fatal, hypersensitivity reactions have been reported in patients receiving cefotaxime. If an allergic reaction occurs, treatment should be discontinued.
The use of cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins.
Since there is a 5–10% cross-allergy between penicillins and cephalosporins, the latter should be used with extreme caution in people who are hypersensitive to penicillin.
It is recommended to prescribe the drug with caution to patients with allergic diathesis or asthma.
Severe bullous skin reactions
Severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported with the use of cefotaxime.
Patients should be advised to seek immediate medical attention if skin or mucosal reactions occur before continuing treatment.
Clostridium difficile-associated diseases (e.g., pseudomembranous colitis)
Diarrhoea, particularly if severe and/or persistent, during treatment or in the first few weeks after treatment may be symptomatic of Clostridium difficile-associated disease. Diseases associated with Clostridium difficile can range in severity from mild to life-threatening, with pseudomembranous colitis being the most severe form of the disease. The diagnosis of this rare but potentially incurable disease can be confirmed by the detection of toxins by endoscopy and/or histological examination. It is important to consider this diagnosis in patients who present with diarrhoea during or after treatment with cefotaxime. If pseudomembranous colitis is suspected, cefotaxime should be discontinued immediately and appropriate specific antibiotic treatment should be initiated immediately.
Fecal stasis may contribute to the development of Clostridium difficile-associated disease. Drugs that inhibit intestinal motility should be avoided.
Hematological reactions
During treatment with cefotaxime, leukopenia, neutropenia and, less frequently, bone marrow depression, pancytopenia and agranulocytosis may develop, especially with prolonged treatment. If treatment lasts longer than 7–10 days, blood counts should be monitored. In case of abnormalities in blood tests (hemogram), treatment should be discontinued.
A few cases of eosinophilia and thrombocytopenia have been reported, which resolved rapidly after discontinuation of treatment. Cases of hemolytic anemia have also been reported.
Patients with renal insufficiency:
Dosage should be adjusted based on estimated creatinine clearance. Caution should be exercised when cefotaxime is administered concomitantly with aminoglycosides, furosemide, probenecid or other nephrotoxic drugs. Renal function should be monitored regularly in these patients, in the elderly and in patients with pre-existing renal impairment.
Neurotoxicity (encephalopathy)
The use of high doses of beta-lactam antibiotics, including cefotaxime, primarily in patients with renal insufficiency, may lead to encephalopathy (impairment/loss of consciousness, abnormal movements, confusion and convulsions).
Patients should be advised to seek medical advice immediately if such reactions occur before continuing treatment.
During post-marketing surveillance, potentially life-threatening arrhythmias have been reported in a very small number of patients receiving cefotaxime by rapid intravenous administration through a central venous catheter. Therefore, the recommended administration or infusion time should be adhered to.
Impact on laboratory test results:
When determining the level of glucose in urine by the reduction method with nonspecific reagents, false-positive results may be obtained. To avoid this, a glucose oxidase test should be used.
Sodium intake
This medicinal product contains 48.18 mg sodium per gram of cefotaxime sodium. Caution should be exercised when administering this medicinal product to patients on a controlled sodium diet.
Ability to influence reaction speed when driving vehicles or other mechanisms
In case of side effects such as dizziness or encephalopathy (e.g., impaired/loss of consciousness, abnormal movements, confusion, and seizures), patients should refrain from driving or operating machinery.
Use during pregnancy or breastfeeding
Cefotaxime crosses the placental barrier. Animal studies have not shown any teratogenic effects of the drug. However, the safety of cefotaxime during human pregnancy has not been established, and the drug should not be used during pregnancy.
The use of the drug in women of childbearing age requires an assessment of the expected benefits and possible risks.
Cefotaxime passes into breast milk.
An effect on the physiological intestinal flora of the infant cannot be excluded, which could lead to diarrhea, colonization with yeast-like fungi, or sensitization of the child.
Therefore, a decision must be made whether to temporarily discontinue breastfeeding or to permanently discontinue treatment, weighing the benefits of breastfeeding for the child and the benefits of treatment for the mother.
Method of administration and doses
The drug is administered intravenously (as a slow injection or infusion) and intramuscularly.
Treatment can be started before the results of the antibiotic sensitivity test are known. Cefotaxime has a synergistic effect in combination with aminoglycosides.
Dosage
Dosage and route of administration depend on the severity of the infection, the sensitivity of the microorganism, and the patient's condition.
Duration of treatment
The duration of treatment with Cefotaxime depends on the clinical condition of the patient and varies depending on the course of the disease.
Treatment should last at least 10 days if the infection is caused by Streptococcus pyogenes (parenteral therapy may be replaced by oral therapy before the end of the 10-day period).
Adults and adolescents (ages 12 to 16–18 years)
Usually 1 g of cefotaxime every 12 hours. In serious infections, the daily dose may be increased to 12 g. Daily doses up to 6 g may be divided into at least two separate administrations at 12-hour intervals. Higher daily doses should be divided into at least 3 or 4 separate administrations at 8 or 6-hour intervals, respectively.
The table below can serve as a guideline for dosage.
| Type of infection | Single dose of cefotaxime | Interval between drug administration | Daily dose of cefotaxime |
| Typical infections where susceptibility of the microorganism has been demonstrated or is expected | 1 g | 12 hours | 2 g |
| Infections where high or moderate susceptibility of various microorganisms has been demonstrated or is expected | 2 g | 12 hours | 4 g |
| Bacterial diseases of unclear etiology that cannot be localized and the patient's condition is critical | 2–3 g | 8 hours 6 hours | 6–9 g 8–12 g |
Infants and children (ages 28 days to 11 years)
Usually 50–100 mg/kg body weight per day, depending on the severity of the infection (up to 150 mg), divided into 2–4 equal doses (every 12–6 hours).
The table below can serve as a guideline for dosage.
| Type of infection | Interval between drug administration | Daily dose of cefotaxime |
| Typical infections where susceptibility of the microorganism has been demonstrated or is expected | 6–12 hours | 50 mg/kg |
| Infections where high or moderate susceptibility of various microorganisms has been demonstrated or is expected | 6–12 hours | 100 mg/kg |
| Bacterial diseases of unclear etiology that cannot be localized and the patient's condition is critical | 6–8 hours | 150 mg/kg* |
(*) In individual cases, especially if there is a threat to life, it may be necessary to increase the daily dose to 200 mg/kg body weight per day. However, the maximum daily dose of 12 grams should not be exceeded.
Premature and full-term newborns (age 0–27 days)
Usually 50 mg/kg body weight per day, divided into 2–4 equal doses (every 12–6 hours). In case of life-threatening situations, an increase in the daily dose may be necessary. In serious infections, 150 mg/kg body weight per day is prescribed.
The table below can serve as a guideline for dosage.
| Type of infection | Age | Interval between drug administration | Daily dose of cefotaxime |
| Typical infections caused by susceptible microorganisms or cases where high or moderate susceptibility has been demonstrated or is expected | 0-7 days 8 days - 1 month | 6–12 hours | 50 mg/kg |
| Bacterial diseases of unclear etiology that cannot be localized and the patient's condition is critical | 0–7 days 8 days - 1 month | 6–12 hours | 150 mg/kg* |
(*) In individual cases, especially if there is a threat to life, it may be necessary to increase the daily dose to 200 mg/kg body weight per day. This dose should not be exceeded due to insufficiently developed renal excretory function (indicator: endogenous creatinine clearance).
Elderly patients
With normal renal and hepatic function, no dose adjustment is required.
Dosage for patients with renal insufficiency
For patients with creatinine clearance less than 10 ml/min after the initial normal dose, maintenance doses should be reduced to half the standard dose without changing the interval between drug administrations.
For patients undergoing hemodialysis: 1 to 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 dialysis session.
For patients undergoing peritoneal dialysis: 1 to 2 g daily, depending on the severity of the infection. Cefotaxime is not removed by peritoneal dialysis.
Other recommendations
Gonorrhea
Single injection (intramuscular or intravenous) of 0.5 g to 1 g cefotaxime. In complicated infections, official recommendations should be followed. Syphilis should be excluded before treatment is initiated.
Urinary tract infections
In case of uncomplicated urinary tract infections: at a dose of 1 g every 12 hours.
Bacterial meningitis
Adults are recommended daily doses of 6 to 12 g per day, divided into equal doses, every 6 to 8 hours. Children are recommended daily doses of 150 to 200 mg/kg body weight per day, divided into equal doses, every 6 to 8 hours. Neonates from 1 to 7 days of life can be given 50 mg/kg of cefotaxime every 12 hours, and neonates from 7 to 28 days of life can be given 50 mg/kg of body weight every 8 hours.
Intra-abdominal infections
Intra-abdominal infections should be treated with cefotaxime in combination with other appropriate antibiotics.
Perioperative prophylaxis
For perioperative prophylaxis of infectious complications, a single dose of 1 to 2 g of cefotaxime is recommended 30–60 minutes before the start of surgery. Another antibiotic is required to protect against anaerobic microorganisms. If the operation lasts longer than 90 minutes, an additional dose is required.
Lyme disease (tick-borne borreliosis)
The daily dose of cefotaxime is 6 g (for 14–21 days). The daily dose is usually divided into three doses (2 g of cefotaxime three times a day).
Method of application
Cefotaxime and aminoglycosides should not be mixed in the same syringe or infusion solution.
Preparation of solutions should be carried out under aseptic (sterile) conditions. Use immediately after preparation.
Intravenous administration
For intravenous (IV) infusion, 1 g or 2 g of the drug is dissolved in 40–100 ml of sterile water for injection or infusion solution. The duration of the infusion is 50–60 minutes.
For intravenous infusion, dissolve 1 g of powder in 8 ml of sterile water for injection. The solution should be injected slowly over 3–5 minutes, as life-threatening arrhythmias may develop when cefotaxime is administered through a central venous catheter.
Intramuscular injection
For intramuscular (IM) injection, cefotaxime is diluted with sterile water for injection in an amount of 4 ml for 1 g. For IM administration, the contents of the cefotaxime vial can be dissolved in water for injection or in 1% lidocaine solution. Then the injection is made deep into the gluteal muscle. In the case of using lidocaine, IV administration of the drug is strictly contraindicated.
Children
Intramuscular administration of the drug is contraindicated in children under 1 year of age.
Overdose
Symptoms of overdose largely correspond to the adverse reaction profile.
There is a risk of developing encephalopathy, particularly in patients with renal insufficiency and when using high doses of beta-lactam antibiotics, including cefotaxime.
In case of overdose, treatment with cefotaxime should be discontinued. Supportive therapy should be initiated, including measures to accelerate the processes of drug elimination from the body, and symptomatic treatment of adverse reactions (e.g., convulsions).
There is no specific antidote. Hemodialysis may reduce the serum concentration of cefotaxime. Peritoneal dialysis is ineffective.
Adverse reactions
The frequency of adverse reactions is defined as follows:
very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1,000, < 1/100); rare (< 1/10,000); frequency unknown (cannot be estimated from the available data).
Infections and infestations: frequency unknown - superinfection.
From the side of the blood and lymphatic system: infrequently - leukopenia, eosinophilia, thrombocytopenia; frequency unknown - bone marrow depression, pancytopenia, neutropenia, agranulocytosis, hemolytic anemia.
On the part of the immune system: infrequently - Jarisch-Herxheimer reaction (exacerbation); frequency unknown - anaphylactic reactions, angioedema, bronchospasm, general malaise, anaphylactic shock.
From the nervous system: infrequently - convulsions; frequency unknown - headache, dizziness, encephalopathy.
Gastrointestinal: uncommon - diarrhea; frequency unknown - nausea, vomiting, abdominal pain, pseudomembranous colitis.
Hepatobiliary disorders: uncommon - increased levels of liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (γ-GT) and/or alkaline phosphatase) and/or bilirubin; frequency unknown - hepatitis* (sometimes with jaundice).
Skin and subcutaneous tissue disorders: uncommon - rash, pruritus, urticaria; frequency unknown - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis.
Renal and urinary disorders: uncommon - decreased renal function/increased creatinine concentration (especially with simultaneous use of aminoglycosides); frequency unknown - acute renal failure, interstitial nephritis.
General disorders and administration site conditions: very common - pain at the injection site (with intramuscular injection); uncommon - fever, inflammatory reactions at the injection site, such as phlebitis/thrombophlebitis.
(*) Post-marketing surveillance.
Jarish-Herxheimer reaction
When treating Lyme disease, a Jarisch-Herxheimer reaction may occur during the first few days of treatment. The following symptoms have been reported after several weeks of Lyme disease treatment: skin rash, itching, fever, leukopenia, elevated liver enzymes, shortness of breath, and joint pain.
Encephalopathy
The use of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal insufficiency, may lead to encephalopathy (with symptoms such as impaired/loss of consciousness, abnormal movements, confusion and convulsions).
Liver and biliary tract disorders
Elevations in liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (γ-GT) and/or alkaline phosphatase) and/or bilirubin have been observed. These values may in isolated cases exceed twice the upper limit of normal and indicate liver damage, usually cholestatic and usually asymptomatic.
Expiration date
3 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
1 g in vials, 10 vials in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyivmedpreparat".
Location of the manufacturer and its business address
Ukraine, 01032, Kyiv, Saksaganskoho St., 139.
