pharmachologic effect
III generation cephalosporin antibiotic for parenteral administration.
It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. Has a wide spectrum of action. Active against gram-positive and gram-negative microorganisms resistant to other antibiotics: Staphylococcus spp. (including Staphylococcus aureus, including penicillinase-forming strains), Staphylococcus epidermidis (excluding Staphylococcus epidermidis and Staphylococcus aureus, methicillin-resistant), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus spp., Enterobacter spp., Escherichia coli, Borrelia burgdorferi, Haemophilus influenzae (including penicillinase-producing strains), Haemophilus parainfluenzae, Moraxella catarrhalis, Klebsiella spp. (including Klebsiella pneumoniae), Morganella morganii, Neisseria meningitidis, Neisseria gonorrhoeae (including penicillinase-producing strains), Acinetobacter spp., Corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, Eubacterium spp., Propionibacterium spp., Clostridium spp. (including Clostridium perfringens), Citrobacter spp., Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri), Serratia spp., some strains of Pseudomonas aeruginosa, Bacteroides spp. (including some strains of Bacteroides fragilis), Fusobacterium spp. (including Fusobacterium nucleatum), Peptococcus spp., Peptostreptococcus spp. Most strains of Clostridium difficile are resistant. Resistant to most beta-lactamases of gram-positive and gram-negative microorganisms.
Pharmacokinetics
After a single intravenous administration in doses of 0.5 g, 1 g and 2 g, the time to reach maximum concentration is 5 minutes, the maximum concentration is 39, 101.7 and 214 mcg/ml, respectively. After intramuscular administration in doses of 0.5 and 1 g, the time to reach the maximum concentration is 0.5 hours and the maximum concentration is 11 and 21 mcg/ml, respectively. Bonding with plasma proteins is 30-50%. Bioavailability - 90-95%. Creates therapeutic concentrations in most tissues (myocardium, bone tissue, gall bladder, skin, soft tissues) and fluids (synovial, pericardial, pleural, sputum, bile, urine, cerebrospinal fluid) of the body. Volume of distribution - 0.25 - 0.39 l/kg. The half-life is 1 hour for intravenous administration and 1 - 1.5 hours for intramuscular administration. Excreted by the kidneys - 20 - 36% unchanged, the rest - in the form of metabolites (15 - 25% - in the form of pharmacologically active desacetylcefotaxime and 20 - 25% - in the form of 2 inactive metabolites - M2 and M3). In chronic renal failure and in the elderly, the half-life increases by 2 times. The half-life in newborns is 0.75-1.5 hours, in premature newborns (body weight less than 1500 g) it increases to 4.6 hours; in children weighing more than 1500 g - 3.4 hours. With repeated intravenous administrations at a dose of 1 g every 6 hours for 14 days, no accumulation is observed. Passes into breast milk.
Cefotaxime powder for solution for injection 1g No. 10
Name
Cefotaxime por. din 1g fl in pack No. 10
Description
White or white with a yellowish tint powder.
Release form
powder for solution for injection
Pharmacological properties
Pharmacodynamics
III generation cephalosporin antibiotic for parenteral administration. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. Has a wide spectrum of action. Typically susceptible species Aerobic gram-positive microorganisms: Staphylococcus aureus (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes. Aerobic gram-negative microorganisms: Borrelia burgdorferi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Morax-ella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Salmonella spp. (including Salmonella typhi), Shigella spp. Anaerobic microorganisms: Fusobacterium species (including Fusobacterium nucleatum), Peptococcus species, Peptostreptococcus species. Species that can acquire resistance Aerobic gram-positive microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis. Aerobic gram-negative microorganisms: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens. Anaerobic microorganisms: Bacteroides fragilis. Resistant microorganisms Aerobic gram-positive microorganisms: Enterococcus species, Listeria monocytogenes, Staphylococcus aureus (methicillin-resistant). Aerobic gram-negative microorganisms: Acinetobacter species, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia. Anaerobic microorganisms: Clostridium difficile. Other microorganisms: Chlamydia species, Chlamydophila species, Mycoplasma species, Treponema pallidum.
Pharmacokinetics
After a single intravenous dose of 0.5 g, 1 g and 2 g TCmax - 5 min, Cmax is 39 mcg/ml, 101.7 mcg/ml and 214 mcg/ml, respectively. After intramuscular administration in doses of 0.5 g and 1 g, TCmax is 0.5 hours and Cmax is 11 μg/ml and 21 μg/ml, respectively. Communication with plasma proteins – 30 – 50%. Bioavailability – 90–95%. Creates therapeutic concentrations in most tissues (myocardium, bone tissue, gallbladder, skin, soft tissues) and fluids (synovial, pericardial, pleural, sputum, bile, urine, cerebrospinal fluid (CSF)) of the body. Volume of distribution – 0.25–0.39 l/kg. Cefotaxime is metabolized in the human body to a significant extent. By acetylation, the active metabolite O-desacetyl-cefotaxime (M1) and two inactive metabolites (M2 and M3) are formed. Metabolite M1 has good antibacterial activity against various pathogens. T1/2 – 1 hour for intravenous administration and 1 – 1.5 hours for intramuscular administration. Excreted by the kidneys - 40-60% unchanged, a small amount of cefotaxime (about 2%) is excreted in bile, the rest - in the form of metabolites (15-25% in the form of pharmacologically active desacetyl-cefotaxime and 20-25% in the form of 2 inactive metabolites – M2 and M3). Pharmacokinetics in special clinical situations: In elderly patients, the half-life is 120–150 minutes. In severe renal failure (creatinine clearance 3–10 ml/min), the half-life of cefotaxime can be increased to 2.5 hours, desacetyl-cefotaxime - up to 10 hours. Under these conditions, cefotaxime accumulates only to a limited extent, in contrast to active and inactive metabolites. Cefotaxime and desacetyl-cefotaxime can be removed from the blood by hemodialysis. In newborns, T1/2 ranges from 0.75 hours to 1.5 hours, in premature newborns it increases to 6.4 hours. In newborns, the pharmacokinetics of cefotaxime depends on the course of pregnancy and chronological age. The half-life in children born at term is increased by approximately 2 times, in premature infants and children with low birth weight - by 2–5 times.
Indications for use
Severe infections caused by bacteria sensitive to cefotaxime: infections of the central nervous system (meningitis), respiratory tract and ENT organs, kidneys and urinary tract, bones, joints, skin and soft tissues, genitals, including uncomplicated gonorrhea (cervical, urethral, rectal ), abdominal organs (including peritonitis), endocarditis, sepsis, Lyme disease (especially stages II and III), with an increased risk of infections in patients after surgical operations (including urological, obstetric-gynecological, gastrointestinal tract ).
Directions for use and doses
Adults and children over 12 years of age (body weight 50 kg or more): The usual recommended dose is 1–2 g of cefotaxime every 12 hours (average 3 g/day) intramuscularly (IM) or intravenously (IV). In severe cases, the daily dose can be increased to 12 g. Daily doses up to 6 g can be divided into at least two equal doses with an interval of 12 hours. Higher daily doses should be divided into at least 3 to 4 single doses at 8 or 6 hour intervals. The duration of treatment depends on the course of the disease. Recommended doses of cefotaxime in certain cases: Gonococcal urethritis, cervicitis: 0.5 g once intramuscularly. Rectal gonorrhea in men: 0.5 g once IM. Rectal gonorrhea in women: 1.0 g once IM. Uncomplicated infections: 2.0 g / day: 1.0 g every 12 hours IM or IV. Moderate to severe infections: 3–6 g/day: 1–2 g every 8 hours IM or IV. Infections that require frequent administration of antibiotics in high doses (for example, septicemia): 6-8 g/day: 2 g every 8 hours IV. Life-threatening infections: up to 12 g/day: 2 g every 4 hours IV. Lyme disease: daily dose is 6 g of cefotaxime (14–21 days). The daily dose is usually divided into 3 single doses (3 times a day, 2 g of cefotaxime), but in some cases it is administered in 2 separate doses (2 times a day, 3 g of cefotaxime). These dosing recommendations are not based on controlled clinical trials but on anecdotal observations. Caesarean section: the first dose - 1 g of cefotaxime - is administered intravenously immediately after clamping the umbilical cord. The second and third doses of cefotaxime - 1 g each should be administered intravenously or intramuscularly 6 and 12 hours after the first dose. In order to prevent the development of infections before surgery, a single dose of 1–2 g of cefotaxime is administered during induction of general anesthesia 30–60 minutes before surgery. Depending on the risk of infection, the same dose may be repeated. Renal dysfunction: if creatinine clearance (CC) is 20 ml/min/1.73 m2 or less, the daily dose is reduced by 2 times. In adult hemodialysis patients, 1 g of cefotaxime administered intravenously at the end of each dialysis session, repeated every 24 hours, is recommended to effectively treat most infections. Children under 12 years of age (weighing less than 50 kg): depending on the severity of the infection, the dose of cefotaxime is from 50 mg to 100 mg (150 mg) per kilogram of body weight per day, divided into equal separate doses administered every 12 (up to 6 ) hourly intervals (2–4 times/day). In some cases, especially in life-threatening situations, it may be necessary to increase the daily dose to 200 mg of cefotaxime per kilogram of body weight. Typically recommended dose regimen: newborns: 0-6 days of life - 50 mg/kg every 12 hours IV, 7-28 days of life - 50 mg/kg every 8 hours IV, infants and children (1 month - 12 years ): children weighing less than 50 kg - 50–180 mg/kg/day IV or IM, divided into four to six single doses. Higher doses should be used for more severe or severe infections, including meningitis. For body weights of 50 kg or more, the usual dose for adults is used. The maximum daily dose should not exceed 12 g. In premature infants, given the immaturity of the kidneys and reduced renal clearance, it is not recommended to exceed a dose of cefotaxime 50 mg per kilogram of body weight per day intravenously. In especially severe cases, the dose can be increased to 100 mg/kg/day. Recommended doses of cefotaxime in selected cases: in children over three months of age: for pneumococcal meningitis during the first 48 to 72 hours: 50 to 75 mg/kg intravenously over 20 minutes every 6 hours (200 to 300 mg/kg/day). Then 15 mg/kg vancomycin IV over 60 minutes (60 mg/kg/day). This regimen may continue beyond 48–72 hours depending on the MIC for the isolated pneumococcal strain. Elderly: Cefotaxime is primarily eliminated by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Since elderly patients are more prone to decreased renal function, particular care should be taken in dose selection, and monitoring of renal function may be helpful. Rules for the preparation of injection solutions To prepare the reconstituted solution, you must use only those solvents that are indicated in the instructions for medical use! Solutions of local anesthetics should not be used as a solvent for preparing solutions for intramuscular and intravenous administration of the drug. Only freshly prepared injection solutions should be used! Before using the medicine, you must check its expiration date. Do not use the medicine after the expiration date indicated on the package. After adding the solvent to the bottle, shake it until the medicine dissolves; after 1-2 minutes the solution will become clear. Before administering the drug, make sure that the solution is clear and does not contain undissolved particles. The drug solution may be colorless or light yellow. Intramuscular injection 1 g of cefotaxime is diluted in 4 ml of water for injection. The drug should be administered deeply intramuscularly. It is not recommended to inject more than 4 ml on one side. If the daily dose of cefotaxime is more than 2 g or the frequency of administration is more than 2 times a day, intravenous administration is recommended. Intravenous injection The contents of the vial are diluted in water for injection in a volume of 10 ml of water for injection. Inject slowly over at least 5 minutes. Intravenous infusion For intravenous infusion, the drug is diluted in water for injection (same as for intravenous injection). After the initial dilution, the drug should be diluted to 50–100 ml in one of the solvents: 0.9% sodium chloride solution, 5% glucose solution, 5% glucose solution with 0.45% sodium chloride solution, 5% glucose solution with 0. 2% sodium chloride solution, lactated Ringer's solution, sodium lactate for injection. Drip administration is carried out for 20–60 minutes. Infusion fluids containing sodium bicarbonate are not recommended due to the instability of cefotaxime in these solutions. Cefotaxime solutions should not be mixed with aminoglycoside solutions. If cefotaxime and aminoglycosides are used simultaneously in the same patient, they should be administered separately and not as a mixed injection/infusion.
Use during pregnancy and lactation
The safe use of cefotaxime during pregnancy has not been established. Animal studies have not shown reproductive toxicity. There are no adequate controlled studies in pregnant women. Cefotaxime crosses the placenta. Therefore, cefotaxime should not be used during pregnancy unless the expected benefits outweigh the potential risks. Lactation Cefotaxime is excreted in breast milk, but in doses significantly lower than therapeutic ones. At the same time, cefotaxime can affect the child's intestinal flora, leading to diarrhea and increased fungal colonization, as well as sensitization of the child. Therefore, cefotaxime should be used with caution in nursing women. If diarrhea, candidiasis or rash occurs in infants while taking cefotaxime, a woman should stop breastfeeding (or use of the drug). Before making a decision, the relationship between the benefits of breastfeeding for the child and the benefits of therapy for the woman should be assessed.
Precautionary measures
1 g of Cefotaxime contains 48 mg of sodium (2.09 mmol), 0.5 g of Cefotaxime contains 24 mg of sodium (1.045 mmol). When given intravenously too quickly (faster than 1 minute), cefotaxime can cause cardiac arrhythmias. Anaphylactic reactions Before starting treatment with cefotaxime, it is necessary to exclude the patient's history of hypersensitivity reactions to cefotaxime, cephalosporins, other beta-lactam antibiotics and drugs. The drug is contraindicated in patients with hypersensitivity to cephalosporins and patients with type I hypersensitivity reactions (anaphylaxis) to other beta-lactam antibiotics. These reactions can be very serious, sometimes fatal. There is evidence of cross-sensitivity between penicillins and cephalosporins in 5–10% of cases. Antibiotics should be used with caution in patients with any manifestations of allergies, especially to drugs. If allergic reactions occur during the use of cefotaxime, it is recommended to stop treatment. Severe hypersensitivity reactions require emergency measures, including the administration of epinephrine. Severe bullous skin reactions Severe cases of blistering reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported in association with the use of cefotaxime. The patient should be informed of the need for medical advice if such reactions occur. Complications associated with Clostridium difficile During or after treatment, pseudomembranous colitis may develop as a result of overgrowth of drug-resistant Clostridium difficile bacteria. If diarrhea occurs, the possibility of this complication should be considered. In mild cases, it is sufficient to discontinue the drug; in severe cases, after stopping the drug, ensure the patient is adequately hydrated, replenish electrolytes, and conduct a study to detect bacteria. If C. difficile is detected, metronidazole or vancomycin should be administered orally. Medicines that inhibit peristalsis should not be used. Caution should be exercised when using cefotaxime in patients with a history of inflammatory bowel disease, especially colitis. Patients with renal insufficiency Patients with renal insufficiency should receive an appropriately reduced dose depending on creatinine clearance. Caution should be exercised if cefotaxime is administered in combination with aminoglycosides or other nephrotoxic drugs. Renal function should be monitored in these patients, in the elderly and in patients with pre-existing renal impairment. Neurotoxic effects High doses of beta-lactam antibiotics, including cefotaxime, especially in patients with renal failure, can cause encephalopathy (impaired consciousness, uncoordinated movements and seizures). Particular vigilance should be exercised in patients with meningitis. The patient should be advised to consult a doctor if such reactions occur. Hematological reactions Leukopenia, neutropenia and rarely agranulocytosis may occur during therapy with cefotaxime, especially if the course of treatment is prolonged. In case of treatment for more than 7-10 days, the white blood cell count should be monitored and treatment should be discontinued if neutropenia occurs. Several cases of eosinophilia and thrombocytopenia have been reported, rapidly resolving after cessation of treatment. Cases of hemolytic anemia, including fatal cases, have also been reported in patients receiving cephalosporins. If a patient develops anemia while taking cefotaxime, treatment should be discontinued until the cause is determined. Monitoring As with any antibiotic use, the use of cefotaxime may lead to the emergence of resistance, which may render the drug ineffective. This must be taken into account in case of recurrent infection and adequate therapy must be prescribed. Effect on laboratory results Cefotaxime, like other cephalosporins, may cause a false-positive Coombs test result. Determination of glucose levels in urine using nonspecific reduction tests may give false-positive results. This phenomenon is not observed when using the oxidase test. Cefotaxime does not interfere with enzyme tests that detect sugar in the urine. During long-term therapy, liver function should be monitored.
Interaction with other drugs
Cefotaxime is pharmaceutically incompatible with solutions of other antibiotics in the same syringe or dropper. Special Problems of INR (International Normalized Ratio) Imbalance Increased activity of oral anticoagulants has been reported in patients receiving antibiotics. Risk factors include infectious or other inflammatory diseases, age and general condition of the patient. Under these conditions, it is difficult to distinguish between the infectious disease and its treatment in causing INR imbalance. However, some classes of antibiotics are more involved: these include fluoroquinolones, macrolides, tetracyclines, co-trimoxazole and some cephalosporins. Other antibiotics In vitro, an antagonistic effect on antibacterial activity has been observed when cefotaxime is combined with bacteriostatic agents (for example, tetracycline, erythromycin, chloramphenicol or sulfonamides). A synergistic effect may be observed in combination with aminoglycosides. Uricosuric drugs Probenecid affects the tubular secretion of cefotaxime in the kidneys, reducing its clearance by half and doubling the effect of cefotaxime in therapeutic doses. Due to the broad therapeutic index of cefotaxime, no dose adjustment is required in patients with normal renal function. Aminoglycosides and diuretics When combined with potentially nephrotoxic drugs (for example, aminoglycosides, polymyxin B and colistin) or potent diuretics (for example, furosemide), cefotaxime, like other cephalosporins, increases the negative effect on the kidneys. Monitoring of renal function is recommended.
Contraindications
Hypersensitivity to cefotaxime or any other cephalosporins. History of severe hypersensitivity reactions (eg, anaphylactic reactions) to any other beta-lactam antibiotic (penicillins, carbapenems, monobactams). With caution: Neonatal period (for intravenous administration), chronic renal failure, ulcerative colitis (including history), pregnancy, lactation (excreted in milk in small concentrations).
Compound
One bottle contains: active substance – cefotaxime (in the form of cefotaxime sodium salt) – 0.5 g or 1.0 g.
Overdose
Symptoms of overdose may correspond to the side effect profile. The most common increases in serum urea and creatinine concentrations were observed. In cases of high doses, there is a risk of reversible encephalopathy with symptoms of central nervous system excitation, myoclonus and convulsions (clonic/tonic). The risk of these side effects increases in patients with severe renal failure, epilepsy and meningitis. Treatment: symptomatic. There is no specific antidote. Cefotaxime serum concentrations can be reduced by hemodialysis or peritoneal dialysis.
Side effect
Allergic reactions: urticaria, chills, fever, rash, itching; rarely - bronchospasm, eosinophilia, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylactic reactions, anaphylactic shock, Jarisch-Herxheimer reaction (fever, chills, headache and joint pain). From the central nervous system: headache, dizziness, encephalopathy, convulsions. Local reactions: phlebitis, pain along the vein during intravenous administration, pain and infiltration during intramuscular administration, inflammatory reactions at the injection/infusion site in the form of thrombophlebitis. From the urinary system: azotemia, oliguria, anuria, increased urea content in the blood, acute renal failure, interstitial nephritis. From the digestive system: nausea, vomiting, diarrhea, constipation, flatulence, abdominal pain, dysbacteriosis; rarely - stomatitis, glossitis, pseudomembranous colitis. From the liver and biliary tract: liver dysfunction (sometimes with jaundice). From the hematopoietic system: leukopenia, neutropenia, granulocytopenia, thrombocytopenia, hemolytic anemia, hypocoagulation, pancytopenia, agranulocytosis. From the cardiovascular system: potentially life-threatening arrhythmias after rapid bolus administration into the central vein. Laboratory indicators: azotemia, increased concentration of urea in the blood, increased activity of “liver” transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, positive Coombs test, increased concentration of lactate dehydrogenase, gamma-glutamyltransferase. Other: superinfection (including candidal stomatitis), acute widespread exanthematous pustulosis. Reporting of Adverse Reactions It is important to report suspected adverse reactions after registration of a medicinal product to ensure continuous monitoring of the benefit-risk profile of the medicinal product. Medical workers are recommended to send information about any suspected adverse reactions, ineffectiveness of the drug and cases of development of antibiotic resistance to the address: Republican Unitary Enterprise "Center for Expertise and Testing in Healthcare", per. Tovarishchesky, 2a, 220037 Minsk, Republic of Belarus
Storage conditions
Store in a place protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children.
Indications for use
Infectious and inflammatory diseases caused by microorganisms sensitive to cefotaxime: infections of the central nervous system (meningitis), respiratory tract and ENT organs, urinary tract, bones, joints, skin and soft tissues (including infected wounds and burns), pelvic organs, peritonitis , bacteremia, septicemia, intra-abdominal infections, endocarditis, Lyme disease, gonorrhea, infections due to immunodeficiency. Prevention of infections after surgical operations (including urological, obstetric-gynecological, gastrointestinal tract).
Contraindications
Hypersensitivity to cefotaxime (including penicillins, other cephalosporins, carbapenems), children (intramuscular administration - up to 2.5 years when using lidocaine as a solvent).
Carefully
Neonatal period (for intravenous administration), chronic renal failure, ulcerative colitis (including history).
Use during pregnancy and breastfeeding
Use during pregnancy is possible only in cases where the potential benefit to the mother outweighs the risk to the fetus. Adequate and strictly controlled studies have not been conducted in pregnant women.
If it is necessary to use the drug during lactation, breastfeeding should be stopped.
special instructions
In the first weeks of treatment, pseudomembranous colitis may occur, manifested by severe, prolonged diarrhea. In this case, stop taking the drug and prescribe adequate therapy, including vancomycin or metronidazole.
Patients with a history of allergic reactions to penicillins may have increased sensitivity to cephalosporin antibiotics.
When treating with the drug for more than 10 days, it is necessary to control the number of blood cells. During treatment with cefotaxime, it is possible to obtain a false-positive Coombs test and a false-positive urine test for glucose.
With the simultaneous use of cephalosporin antibiotics and ethanol, the development of disulfiram-like reactions is possible, however, in clinical studies of cefotaxime (Claforan), no such effect was recorded when used simultaneously with ethanol.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, you should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Instructions for use CEFOTAXIM (CEFOTAXIME)
Before prescribing Cefotaxime, it is necessary to collect an allergic history, especially regarding indications of allergic diathesis, hypersensitivity reactions to beta-lactam antibiotics. Cross-allergy between penicillins and cephalosporins is known, which occurs in 5-10% of cases. If hypersensitivity reactions occur, the drug is discontinued. Emergency measures for the development of anaphylactic shock:
- ensuring airway patency (intubation if necessary), oxygen therapy, adrenaline, glucocorticoids.
Caution should be exercised when treating patients with a history of gastrointestinal diseases. Avoid prescribing the drug for coprostasis. In the first weeks of treatment, pseudomembranous colitis may occur, manifested by severe, prolonged diarrhea. The diagnosis is confirmed by colonoscopy and/or histological examination. This complication is regarded as very serious; Cefotaxime is immediately discontinued and adequate therapy is prescribed. Emergency measures:
- restoration of water and electrolyte balance; if necessary, antibiotics active against C. difficile are prescribed orally (including the use of vancomycin or metronidazole orally). Loperamide should not be prescribed.
Like other cephalosporins, Cefotaxime may cause a positive direct Coombs test result. When determining the level of glucose in urine using the recovery method, false positive results may be obtained. To avoid this, an enzymatic method should be used.
During treatment with Cefotaxime, especially over a long period, hematological reactions may develop - leukopenia, neutropenia, and less commonly - agranulocytosis. If the course of treatment lasts more than 7-10 days, the number of leukocytes in the blood should be monitored. Treatment should be discontinued in case of neutropenia. Some cases of eosinophilia and thrombocytopenia are quickly reversible after discontinuation of drug treatment. There are also cases of hemolytic anemia.
For patients with renal failure, the dose should be adjusted taking into account creatinine clearance. Caution should be exercised when prescribing the drug together with aminoglycosides or other nephrotoxic drugs. For such patients, as well as for elderly patients and patients with pre-existing renal failure, monitoring of renal function during use of the drug is necessary.
The use of high doses of beta-lactam antibiotics, including cefotaxime, especially in people with renal failure, can lead to encephalopathy (for example, impaired consciousness, impaired movement and seizures). In such cases, the patient is advised to immediately consult a doctor before continuing antibiotic treatment. Potentially life-threatening arrhythmias occurred in a very small number of patients in whom cefotaxime was administered rapidly through a central venous catheter. Therefore, the recommended time for injections or infusions of the drug must be observed.
Since the drug is presented in the form of the sodium salt of cefotaxime, it is necessary to take into account the content of sodium ions (48.2 mg/g) when using it.
Children
When prescribing the drug to premature and newborn children, special care should be taken.
The ability to influence the reaction speed when driving a vehicle or a robot with other mechanisms
To date, there is no evidence that Cefotaxime directly affects the ability to drive a car or use other mechanical means. The use of high doses of cefotaxime, especially in patients with renal failure, can lead to encephalopathy (for example, impaired consciousness, impaired movement and convulsions). If such cases occur, patients are advised to refrain from driving a car or using other mechanical means.
Directions for use and doses
For adults and children weighing 50 kg or more: for uncomplicated infections - intramuscularly or intravenously, 1 g every 12 hours; for uncomplicated acute gonorrhea - intramuscularly, 0.5 - 1 g once; for moderate infections - intramuscularly or intravenously, 1 - 2 g every 8 hours; for sepsis - intravenously, 2 g every 6 - 8 hours, for life-threatening infections (meningitis) - intravenously, 2 g every 4 hours, maximum daily dose - 12 g. The duration of treatment is determined individually.
In order to prevent the development of infections before surgery, 1 g is administered once during induction of general anesthesia. If necessary, the administration is repeated after 6 - 12 hours.
For caesarean section (at the time of clamping the umbilical vein) - 1 g intravenously, then 6 and 12 hours after the first dose - an additional 1 g.
When creatinine clearance is 20 ml/min/1.73 sq.m or less, the daily dose is reduced by 2 times.
Premature and newborns up to 1 week - intravenously 50 mg/kg every 12 hours; at the age of 1 - 4 weeks - intravenously 50 mg/kg every 8 hours; children weighing up to 50 kg - intravenously or intramuscularly 50 - 180 mg/kg in 4 - 6 injections. For severe infections, including meningitis, the daily dose is increased to 100 - 200 mg/kg, intramuscularly or intravenously, in 4 - 6 doses, the maximum daily dose is 12 g.
Rules for preparing injection solutions: for intravenous injection, water for injection is used as a solvent (1 g diluted in 4 ml of solvent); for intravenous infusion, 0.9% sodium chloride solution or 5% dextrose solution is used as a solvent (1 g diluted in 50 - 100 ml of solvent). The duration of the infusion is 50 - 60 minutes. For intramuscular administration, use water for injection or 1% lidocaine solution (1 g diluted in 4 ml of solvent).
Cefotaxime 1g For Injection
Cefotaxime 1g for injection
Instructions for use and dosage The drug is administered intravenously (stream or drip (in a dropper) and intramuscularly. The drug is prescribed to adults and children over 12 years of age (with body weight ≥50 kg) For uncomplicated infections, as well as for urinary tract infections - intravenously m or IV 1 g every 8-12 hours. For uncomplicated acute gonorrhea - IM in a dose of 1 g once. For moderate infections - IM or IV 1-2 g every 12 hours. severe infections, for example, with meningitis - 2 g IV every 4-8 hours, the maximum daily dose is 12 g. The duration of treatment is determined individually. In order to prevent the development of infections before surgery, it is administered during induction anesthesia in a single dose of 1 d. If necessary, the administration is repeated after 6-12 hours. For caesarean section - at the time of applying clamps to the umbilical vein - IV at a dose of 1 g, then 6 and 12 hours after the first dose - an additional 1 g. Premature and for newborns under 1 week of age - IV at a dose of 50 mg/kg every 12 hours; at the age of 1-4 weeks - IV at a dose of 50 mg/kg every 8 hours. Children weighing ≤50 kg - IV or IM (children over 2.5 years old) 50-180 mg/kg IV 4-6 injections. In case of severe infections (including meningitis), the daily dose when prescribed to children is increased to 100-200 mg/kg, IM or IV for 4-6 injections, the maximum daily dose is 12 g. Rules for the preparation of injections solutions (how to dilute Cefotaxime) For intravenous injection: 1 g of the drug is diluted in 4 ml of sterile water for injection; the drug is administered slowly over 3-5 minutes. For intravenous infusion: 1-2 g of the drug is diluted in 50-100 ml of solvent. The solvent used is 0.9% sodium chloride solution or 5% dextrose (glucose) solution. Duration of infusion - 50 - 60 minutes. For intramuscular administration: 1 g is dissolved in 4 ml of solvent. Water for injection or a 1% solution of lidocaine (novocaine) is used as a solvent. Release forms Powder for the preparation of a solution for intravenous and intramuscular administration (injections in injection ampoules) 250 mg, 500 mg and 1 gram of powder for dilution in water for injection or novocaine. Cefotaxime is a 3rd generation cephalosporin antibiotic with a broad spectrum of action. It has a bactericidal effect by inhibiting the synthesis of bacterial cell walls. The mechanism of action is due to acetylation of membrane-bound transpeptidases and disruption of peptidoglycan cross-linking, which is necessary to ensure the strength and rigidity of the cell wall. Highly active against gram-negative bacteria (resistant to other antibiotics): Escherichia coli (Escherichia coli), Citrobacter spp., Proteus mirabilis, Providencia spp., Klebsiella spp., Serratia spp., some strains of Pseudomonas spp., Haemophilus influenzae. Less active against Streptococcus spp. (including Streptococcus pneumoniae), Staphylococcus spp., Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides spp. Resistant to most beta-lactamases. Pharmacokinetics: Rapidly absorbed from the injection site. Plasma protein binding is 40%. Widely distributed in tissues and body fluids. Reaches therapeutic concentrations in the cerebrospinal fluid, especially in meningitis. Penetrates the placental barrier and is excreted in breast milk in low concentrations. 40-60% of the dose is excreted unchanged in the urine after 24 hours, 20% in the form of metabolites. Indications Infectious and inflammatory diseases caused by sensitive microorganisms, including: central nervous system infections (meningitis); infections of the respiratory tract and ENT organs; urinary tract infections; bone and joint infections; skin and soft tissue infections; pelvic organ infections; abdominal infections; peritonitis; sepsis; endocarditis; gonorrhea; infected wounds and burns; salmonellosis; Lyme disease; infections due to immunodeficiency; prevention of infections after surgical operations (including urological, obstetric and gynecological, on the gastrointestinal tract). Contraindications : pregnancy; children up to 2.5 years of age (for intramuscular administration); hypersensitivity (including to penicillins, other cephalosporins, carbapenems). Special instructions In the first weeks of treatment, pseudomembranous colitis may occur, manifested by severe, prolonged diarrhea. In this case, stop taking the drug and prescribe adequate therapy, including vancomycin or metronidazole. Patients with a history of allergic reactions to penicillins may have increased sensitivity to cephalosporin antibiotics. When treating with the drug for more than 10 days, monitoring of the peripheral blood picture is necessary. During treatment with cefotaxime, it is possible to obtain a false-positive Coombs test and a false-positive urine test for glucose. During treatment, you should not drink alcohol, since effects similar to those of disulfiram are possible (facial hyperemia, spasms in the abdomen and stomach, nausea, vomiting, headache, decreased blood pressure, tachycardia, shortness of breath). Side effect : headache; dizziness; renal dysfunction; oliguria; nausea, vomiting; diarrhea or constipation; flatulence; abdominal pain; dysbacteriosis; stomatitis; glossitis; pseudomembranous enterocolitis; hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, agranulocytosis; potentially life-threatening arrhythmias following rapid central venous bolus administration; increased concentration of urea in the blood; positive Coombs reaction; phlebitis; pain along the vein; pain and infiltration at the site of intramuscular injection; hives; chills or fever; rash; skin itching; bronchospasm; eosinophilia; anaphylactic shock; superinfection (vaginal and oral candidiasis). Drug interactions Cefotaxime increases the risk of bleeding when combined with antiplatelet agents and nonsteroidal anti-inflammatory drugs. The risk of kidney damage increases with simultaneous use of aminoglycosides, polymyxin B and loop diuretics. Drugs that block tubular secretion increase plasma concentrations of cefotaxime and slow down its elimination. Pharmaceutical interactions Pharmaceutically incompatible with solutions of other antibiotics in the same syringe or dropper. Use in children Contraindicated in children under 2.5 years of age (for intramuscular administration). Use during pregnancy and lactation Cefotaxime is contraindicated for use during pregnancy.
Side effect
Allergic reactions: urticaria, chills or fever, rash, itching, bronchospasm, eosinophilia, erythema malignant exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), angioedema, anaphylactic shock.
From the nervous system: headache, dizziness, encephalopathy, movement disorders, convulsions.
From the urinary system: impaired renal function, oliguria, interstitial nephritis.
From the digestive system: nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, dysbacteriosis, liver dysfunction, stomatitis, glossitis, pseudomembranous colitis, hepatitis, jaundice.
From the hematopoietic organs: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, hypocoagulation, agranulocytosis.
From the cardiovascular system: potentially life-threatening arrhythmias after rapid bolus administration into the central vein.
Laboratory indicators: azotemia, increased urea concentration in the blood, increased activity of “liver” transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, false-positive Coombs test.
Other: superinfection (in particular, candidal vaginitis).
Local reactions: phlebitis, pain along the vein, pain and infiltration at the site of intramuscular injection.
Overdose
Symptoms: convulsions, encephalopathy (in case of large doses, especially in patients with renal failure), tremor, increased neuromuscular excitability.
Treatment: symptomatic, maintenance of vital functions. There is no specific antidote.
Cefotaxime
Classification of undesirable side reactions by frequency of development, according to the recommendations of the World Health Organization: very often (≥10%); often (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%); very rare (<0.01%); frequency unknown (based on available data, it is impossible to estimate the frequency of side effects).
Infectious and parasitic diseases
Frequency unknown: superinfections. As with the prescription of other antibiotics, the use of cefotaxime, especially long-term, can lead to excessive growth of non-susceptible 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
Uncommon: leukopenia, eosinophilia, thrombocytopenia.
Frequency unknown: bone marrow hematopoietic failure, pancytopenia, neuropenia, agranulocytosis, hemolytic anemia.
Immune system disorders
Uncommon: Jarisch-Herxheimer reaction. As with the use of other antibiotics, when treating borreliosis, the development of a Jarisch-Herxheimer reaction is possible during the first days of therapy. There are reports of the occurrence of one or more symptoms after a few weeks of treatment for borreliosis: skin rash, itching, fever, leukopenia, increased activity of liver enzymes, difficulty breathing, 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 for which the patient is receiving treatment.
Frequency unknown: anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock.
Nervous system disorders
Uncommon: convulsions.
Not known: encephalopathy (eg, impaired consciousness, impaired motor activity), headache, dizziness.
Heart disorders
Frequency unknown: arrhythmias (due to rapid bolus administration through a central venous catheter).
Gastrointestinal disorders
Uncommon: diarrhea.
Frequency unknown: nausea, vomiting, abdominal pain, pseudomembranous colitis.
Disorders of the liver and biliary tract
Uncommon: increased activity of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], gamma-glutamyl transferase [gamma-GT], alkaline phosphatase [AL]) and/or bilirubin concentration. These laboratory abnormalities (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
Uncommon: rash, itching, urticaria.
Frequency unknown: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis.
Renal and urinary tract disorders
Uncommon: decreased renal function/increased creatinine concentration, especially when combined with aminoglycosides.
Frequency unknown: acute renal failure, interstitial nephritis.
General and administration site disorders
Often: pain at the injection site (with intramuscular injection).
Uncommon: fever, inflammatory reactions at the injection site, including phlebitis/thrombophlebitis.
Frequency unknown: With intramuscular administration, 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 overdose.
Interaction with other drugs
Pharmaceutically incompatible with solutions of other antibiotics in the same syringe or dropper.
Increases the risk of bleeding when combined with antiplatelet agents and non-steroidal anti-inflammatory drugs.
The likelihood of kidney damage increases when taken simultaneously with aminoglycosides, polymyxin B and loop diuretics.
Drugs that block tubular secretion increase plasma concentrations of cefotaxime and slow down its elimination.
