Cefotaxime-Vista powder for solution for injection 1000 mg vial No. 10

Instructions Cefotaxime-Vista powder for solution for injection 1000 mg vial No. 10

Composition

active ingredient: cefotaxime;

1 bottle contains

cefotaxime sodium 1.048 g, which corresponds 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. Beta-lactam antibiotics. Third-generation cephalosporins. Cefotaxime. 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.

Mechanism of resistance: Bacterial resistance to cefotaxime may result from one or more of the mechanisms listed below.

Hydrolysis by beta-lactamases: 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).

Breakpoints: The minimum inhibitory concentration (MIC) breakpoints for cefotaxime recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which distinguish susceptible from resistant organisms, are given in Table 1.

Table 1

Clinical breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cefotaxime

Spectrum of antibacterial activity. The prevalence of resistance may vary regionally and over time for selected species. Local information on resistance should be taken into account when treating serious infections. Specialist advice should be sought as necessary when the local prevalence of resistance is such that the benefit of use is questionable.

Pharmacokinetics.

After intramuscular administration of cefotaxime, its maximum serum concentration (approximately 20 mg/l after 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 a low percentage (the concentration in breast milk is 0.4 mg/l after 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 binds to blood plasma proteins by approximately 25-40%.

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 not detectable in urine or plasma for a short time, as it is rapidly converted to the stereoisomers of the lactone with an open ring structure (beta-lactam ring). These are also excreted in the urine. Excretion. Cefotaxime and desacetylcefotaxime are excreted mainly by the kidneys. A small percentage (approximately 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 excreted in the urine, of which 50-60% was unchanged and the rest was excreted 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 minutes 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 only slightly under these conditions, in contrast to the active and inactive metabolites.

Both cefotaxime and desacetylcefotaxime are removed to a significant extent from the blood by hemodialysis.

Indication

For the treatment of the following serious infections caused or likely to be caused by organisms susceptible to cefotaxime:

Bacterial pneumonia (cefotaxime is not active against bacteria that cause atypical pneumonia or against various other bacterial strains that can cause atypical pneumonia, including P. aeruginosa (see section "Pharmacodynamics")).

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).

Bacteremia associated or suspected to be associated with one of the listed infections (if the infection is caused by Gram-negative bacteria, this medicinal product should be combined with another appropriate antibiotic).

Endocarditis (if the infection is caused by gram-negative bacteria, this medicine 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 pronounced risk of postoperative infections). Official recommendations on the correct 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).

Interaction with other medicinal products and other types of interactions

With simultaneous use with nephrotoxic drugs (aminoglycosides) and potent diuretics (ethacrynic acid, furosemide), colistin, polymyxin increases the risk of developing renal failure. In these patients, renal function should be monitored.

During treatment with cefotaxime, the effectiveness of oral contraceptives may be reduced, so additional contraception should be used during this period. Cefotaxime should not be used together with bacteriostatic antibiotics (e.g. tetracyclines, erythromycin and chloramphenicol) because of the possible antagonistic effect.

In combination therapy, cefotaxime solutions should not be mixed with aminoglycoside solutions; they should be administered separately.

Concomitant use of nifedipine increases the bioavailability of cefotaxime by 70%. Probenecid blocks the tubular secretion of cefotaxime and prolongs its half-life, which increases cefotaxime exposure by approximately twofold and reduces renal clearance by approximately 50% at therapeutic doses.

Due to the wide therapeutic range of cefotaxime, dosage adjustment is not required in patients with normal renal function.

Patients with impaired renal function may require dosage adjustment. Cefotaxime-Vista should not be used with lidocaine:

with intravenous administration;

children under 30 months of age;

patients with a history of hypersensitivity to lidocaine;

patients with heart block;

patients with severe heart failure.

Impact on laboratory test results

A false-positive Coombs test may occur during therapy with cephalosporins; this phenomenon may also occur during treatment with cefotaxime and may interfere with cross-matching of blood.

It is recommended to use glucose oxidase methods for determining blood sugar levels due to the possibility of false-positive results when using non-specific reagents (Benedict, Fehling or Klinikest). The possibility of reducing cefotaxime clearance exists for mezlocillin and azlocillin.

Application features

Cefotaxime-Vista should be prescribed with caution in cases of impaired renal or hepatic function, with a history of hypersensitivity to penicillins. In cases of impaired renal function, the dose of the drug should be reduced, taking into account the severity of renal failure and the sensitivity of the pathogen. With prolonged use of the drug, it is necessary to monitor renal function and prevent dysbacteriosis. It is advisable to regularly monitor the cellular composition of peripheral blood and liver function. During the use of the drug, a false-positive Coombs test may develop.

Anaphylactic reactions.

The use of cephalosporins requires clarification of the allergic history (allergic diathesis, asthma, hypersensitivity reactions to beta-lactam antibiotics). If a patient develops a hypersensitivity reaction, treatment should be discontinued. The use of cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins. In case of any doubt, the presence of a doctor at the first administration of the drug is mandatory due to the possible development of an anaphylactic reaction. Cross-allergy between cephalosporins and penicillins is known, which occurs in 5-10% of cases. The drug should be used with extreme caution in patients with a history of allergy to penicillins.

Pseudomembranous colitis.

Pseudomembranous colitis may occur in the first weeks of treatment, manifested by severe prolonged diarrhea. The diagnosis is confirmed by colonoscopy and/or histological examination. These complications are considered quite serious: the drug should be immediately discontinued and adequate therapy should be prescribed, including oral vancomycin or metronidazole. The combination of cefatoxime with nephrotoxic drugs requires monitoring of renal function, and use for more than 10 days requires monitoring of blood composition. Elderly and debilitated patients should be prescribed vitamin K (prevention of hypocoagulation).

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 and/or mucosal reactions occur before continuing treatment. Clostridium difficile-associated diseases (e.g. pseudomembranous colitis) The occurrence of 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. Clostridium difficile-associated diseases 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 toxin detection, 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 treatment should be discontinued immediately and appropriate specific antibiotic treatment should be initiated immediately.

Fecal stasis can lead to the development of Clostridium difficile-associated diseases. The use of drugs that inhibit intestinal peristalsis should be avoided.

During treatment with cefotaxime, leukopenia, neutropenia, and less often 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 counts (hemogram), treatment should be discontinued. Several 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 failure.

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 elderly patients and in patients with pre-existing renal insufficiency.

Neurotoxicity (encephalopathy).

Particularly in patients with renal insufficiency, high doses of beta-lactam antibiotics, including cefotaxime, may lead to encephalopathy (impairment/loss of consciousness, abnormal movements, confusion and convulsions). Patients should be advised to seek immediate medical attention 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 times should be adhered to.

As with other broad-spectrum antibiotics, prolonged use of Cefotaxime-Vista may result in overgrowth of non-susceptible organisms, necessitating discontinuation of treatment. If superinfection occurs during treatment, antimicrobial therapy should be used. False-positive results may be obtained when determining the level of glucose in urine by the recovery method. To prevent this, an enzyme test should be used.

During treatment, alcohol should not be consumed, as effects similar to those of disulfiram are possible (facial hyperemia, abdominal and stomach cramps, nausea, vomiting, headache, decreased blood pressure, tachycardia, difficulty breathing).

Important information about excipients.

This medicinal product contains 2.2 mmol (or 50.5 mg) sodium per gram of powder for solution for injection. Caution should be exercised when administering this medicinal product to patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Pregnancy.

Cefotaxime crosses the placental barrier. Animal studies have not shown any teratogenic effects of cefotaxime. However, the safety of cefotaxime during human pregnancy has not been established, and the drug should not be used during pregnancy.

Breastfeeding period.

Cefotaxime passes into breast milk. An effect on the physiological intestinal flora of the infant cannot be excluded, which could lead to diarrhoea, colonization with yeast-like fungi or sensitization of the infant. Therefore, a decision must be made whether to temporarily discontinue breast-feeding or to permanently discontinue treatment, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.

Fertility.

The use of the drug in women of childbearing age requires an assessment of the expected benefits and possible risks.

Ability to influence reaction speed when driving vehicles or other mechanisms

Due to the possibility of adverse reactions such as dizziness or encephalopathy (e.g., impaired/loss of consciousness, abnormal movements, confusion, and seizures), patients should avoid driving or operating machinery during treatment.

Method of administration and doses

The drug is intended for intravenous jet, drip and intramuscular administration.

For intravenous infusion, dissolve 1 g of powder in 8 ml of sterile water for injection. Administer slowly over 3-5 minutes due to the possible development of life-threatening arrhythmias when cefotaxime is administered through a central venous catheter.

For intravenous infusion, dissolve 1 g or 2 g of powder in 40-100 ml of 0.9% sodium chloride solution or 5% glucose solution. The infusion duration is 50-60 minutes. For intramuscular administration, dissolve 1 g of powder in 4 ml of sterile water for injection or 1% lidocaine solution and inject deeply into the gluteal muscle. In case of using lidocaine, intravenous administration of the drug is strictly contraindicated.

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 susceptibility of the microorganism, and the patient's condition.

The duration of use of Cefotaxime-Vista 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 (aged 12 to 16 18 years).

Cefotaxime is usually administered at a dose of 1 g every 12 hours. In severe 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 12-hour intervals. Higher daily doses should be divided into at least 3 or 4 separate administrations at 8 or 6-hour intervals, respectively.

Table 2 can be a guideline for dosage.

Table 2

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).

Table 3 can be a guideline for dosage.

Table 3

* In some cases, especially in life-threatening situations, 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).

The usual dose is 50 mg/kg/day, divided into 2-4 equal doses (every 12-6 hours). In life-threatening situations, an increase in the daily dose may be necessary. In serious infections, 150 mg/kg/day is prescribed. Table 4 can be used as a guide for dosing.

Table 4

* In individual cases, especially in life-threatening situations, 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 kidney and liver function, there is no need to adjust the dose.

Dosage in patients with renal insufficiency.

In 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.

In patients undergoing hemodialysis: 1 g 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.

In patients undergoing peritoneal dialysis: 1 g to 2 g per day, depending on the severity of the infection. Cefotaxime is not removed by peritoneal dialysis.

Other recommendations.

Gonorrhea. Single administration (intramuscularly or intravenously) of 0.5 g to 1 g cefotaxime. In complicated infections, official recommendations should be considered. Syphilis should be excluded before treatment. Urinary tract infections. In uncomplicated urinary tract infections: 1 g every 12 hours.

Perioperative prophylaxis. For perioperative prophylaxis of infectious complications, a single dose of 1 g to 2 g of cefotaxime is recommended 30 to 60 minutes before surgery. Another antibiotic is required to protect against anaerobic organisms. If the surgery lasts longer than 90 minutes, an additional dose is required.

Method of application.

Cefotaxime and aminoglycosides should not be mixed in the same syringe or infusion solution. The solutions should be prepared under aseptic (sterile) conditions. Use immediately after preparation.

Children.

Do not administer the drug intramuscularly to children under 1 year of age.

Overdose

Symptoms: possible fever, leukopenia, thrombocytopenia, acute hemolytic anemia, skin, gastrointestinal and liver reactions, shortness of breath, renal failure, stomatitis, anorexia, temporary hearing loss, loss of spatial orientation, encephalopathy (especially in renal failure and when using high doses of beta-lactam antibiotics, including cefotaxime). In isolated cases, convulsions are observed, as well as increased side effects.

Treatment. There is no specific antidote. Serum cefotaxime levels can be reduced by hemodialysis. Peritoneal dialysis is not effective. If necessary, symptomatic therapy should be carried out.

If anaphylactic shock occurs, appropriate measures should be taken immediately. At the first signs of a hypersensitivity reaction (skin rash, urticaria, headache, nausea, loss of consciousness), cefotaxime administration should be discontinued. In the event of a severe hypersensitivity reaction or anaphylactic reaction, appropriate therapy should be initiated (administration of epinephrine and/or glucocorticoids). In other clinical conditions, additional measures may be required, such as artificial respiration, the use of histamine receptor antagonists. In the event of vascular insufficiency, resuscitation measures should be taken.

Adverse reactions

The frequency of adverse reactions is defined as follows: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), and frequency unknown (cannot be estimated from the available data).

Table 5

* Post-marketing surveillance.

Jarisch-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.

From the liver and biliary tract.

Elevations in liver enzymes (ALT, AST, LDH, 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 with an asymptomatic course.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Expiration date

3 years.

Storage conditions

Store in the original packaging to protect from light at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Incompatibility.

The solution of the drug is incompatible with solutions of other antibiotics, aminoglycoside solutions in the same syringe or dropper. For dilution, use the solutions specified in the section "Method of administration and doses".

Packaging

1 g of powder in a vial; 1 or 10 vials in a cardboard box.

Vacation category

According to the recipe.

Producer

ACS DOBFAR S.P.A.

Location of the manufacturer and address of its place of business.

VIA ALESSANDRO FLEMING, 2, VERONA (VR), 37135, Italy.