INSTRUCTIONS FOR MEDICAL USE ASTAPIM ™ Trade name of the drug: ASTAPIM™ Active substance (INN): cefepim Dosage form: powder for the preparation of a solution for injection. Composition: Each bottle contains: active substance: Sterile cefepime hydrochloride equivalent (buffered with L-arginine) to cefepime 1000 mg Description: white to yellowish powder Pharmacotherapeutic group: Antibiotic (gr.cephalosporins) ATX Code: J01DE01
Pharmacological properties Pharmacodynamics Cefepim, the active substance of the drug ASTAPIM, is an antibiotic of the fourth generation cephalosporin group with a wide spectrum of action for intramuscular or intravenous administration. Mechanism of action Cefepime acts bactericidal, inhibiting the synthesis of the cell wall. Cefepime is active against various gram-positive and gram-negative bacteria, including most strains resistant to aminoglycosides or third-generation cephalosporins. Pharmacodynamic effects Cefepime has high resistance to hydrolysis of most β-lactamases, low affinity for β-lactamases encoded by chromosomal genes, and quickly penetrates gram-negative bacterial cells. Inside bacterial cells, the molecular targets of cefepime are penicillin-binding proteins (PBP). In studies with Escherichia coli and Enterobacter cloacae, cefepime had the highest affinity for PBP3, PBP2, PBP1a and PBP1b. Binding to PBP2 occurred with a significantly higher degree of affinity compared to other parenteral cephalosporins, which may increase the antibacterial activity of cefepime. The moderate affinity of cefepime for PBP1a and PBP1b may also contribute to its overall antibacterial activity. ASTAPIM is active against a wide range of microorganisms. The ratio of the minimum bactericidal concentration to the minimum inhibitory concentration (MBC/MIC) for cefepime for more than 80% of isolates of all gram-positive and gram-negative microorganisms studied is ≤ 2. In vitro studies on Pseudomonas aeruginosa isolates revealed a synergistic effect of cefepime with aminoglycosides. The prevalence of resistance of individual bacterial strains may vary geographically and over time. Therefore, it is advisable to take into account information about the resistance of microorganisms for a specific area before starting treatment. The drug is active against the following microorganisms: - aerobic gram-positive microorganisms: Staphylococcus aureus (including beta-lactamase-producing strains), Staphylococcus epidermidis (including beta-lactamase-producing strains), other staphylococcus strains, including Staphylococcus hominis, Staphylococcus saprophyticus; Streptococcus pyogenes (group A streptococci), Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae (including strains with moderate resistance to penicillin - MIC is 0.1-1 mcg/ml), other beta-hemolytic streptococci (groups C, G, F), Streptococcus bovis (group D), streptococci groups Viridans. Note: Most strains of enterococci, for example, Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to most cephalosporin antibiotics, including cefepim. - aerobic gram-negative microorganisms: Acinetobacter calcoaceticus (subspecies anitratus, lwoffii), Aeromonas hydrophila, Capnocytophaga sp., Citrobacter sp. (including Citrobacter diversus, Citrobacter freundii), Campylobacter jejuni, Enterobacter sp. (including Enterobacter cloacae, Enterobacter aerogenes, Enterobacter sakazakii), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella sp. (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae), Legionella sp., Morganella morganii, Moraxella catarrhalis (Branhamella catarrhalis, including beta-lactamase-producing strains); Neisseria gonorrhoeae (including beta-lactamase-producing strains β-lactamase), Neisseria meningitidis, Pantoea agglomerans (formerly known as Enterobacter agglomerans), Proteus sp. (including Proteus mirabilis, Proteus vulgaris), Providencia sp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas sp. (including Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri), Salmonella sp., Serratia sp. (including Serratia marcescens, Serratia liquefaciens), Shigella sp., Yersinia enterocolitica. Note: Cefepime is inactive against many strains of Stenotrophomonas maltophilia (formerly known as Xanthomonas maltophilia (Pseudomonas maltophilia)). - anaerobic microorganisms: Bacteroides sp., Clostridium perfringens, Fusobacterium sp., Mobiluncus sp., Peptostreptococcus sp., Prevotella melaninogenica (formerly known as Bacteroides melaninogenicus), Veillonella sp. Note: Cefepime is inactive against Bacteroides fragilis and Clostridium difficile. Pharmacokinetics Adult Distribution The average concentrations of cefepime in blood plasma in adult healthy men at various times after a single 30-minute intravenous or intramuscular injection in doses of 0.5 g, 1 g and 2 g are shown in the table below. Average plasma concentrations of cefepime (mg/ml) in adult healthy men The dose of cefepime is 0.5 hours 1 hour 2 hours 4 hours 8 hours 12 hours Intravenous administration 0.5 g 38.2 21.6 11.6 5.0 1.4 0.2 1 g 78.7 44.5 24.3 10.5 2.4 0.6 2 g 163.1 85.8 44.8 19.2 3.9 1.1 Intramuscular injection 0.5 g 8.2 12.5 12.0 6.9 1.9 0.7 1 g 14.8 25.9 26.3 16.0 4.5 1.4 2 g 36.1 49.9 51.3 31.5 8.7 2.3 Absorption Cefepim is completely absorbed after intramuscular administration. Therapeutic concentrations of cefepime in various tissues and fluids are shown in the table below.
Average concentrations of cefepime in various body fluids (mcg/ml) and in tissues (mcg/g) in adult healthy men Body fluids and tissues Dose (IV) Average time sampling (hours) after dosing Average concentration Urine 0.5 g 1 g 2 g 0-4 0-4 0-4 292 926 3120 Bile 2 g 9.4 17.8 Peritoneal fluid 2 g 4.4 18.3 Liquid blisters 2 g 1.5 81.4 Bronchial mucosa 2 g 4.8 24.1 Sputum 2 g 4.0 7.4 Prostate 2 g 1.0 31.5 Appendix 2 g 5,7 5,2 Gallbladder 2 g 8,9 11,9 Metabolism/excretion Cefepime is metabolized to N-methylpyrrolidine, which is rapidly converted to N-methylpyrrolidine oxide. Approximately 85% of the administered dose of unchanged cefepime, less than 1% of N-methylpyrrolidine, 6.8% of N-oxide and 2.5% of the cefepime epimer are detected in urine. The degree of binding of cefepime to serum proteins averages 16.4% and does not depend on the concentration of the drug in the blood serum. After administration of doses from 250 mg to 2 g, the half-life (T1 / 2) of cefepime from the body is on average about 2 hours. In healthy volunteers who received cefepime in doses up to 2 g intravenously at intervals of 8 hours for 9 days, there was no accumulation of cefepime in the body. The average total clearance is 120 ml/min. Cefepim is excreted almost completely by the kidneys, mainly by glomerular filtration (the average renal clearance is 110 ml / min). Pharmacokinetics in special groups of patients Patients with cystic fibrosis Clinically significant improvement was noted in patients with cystic fibrosis who took cefepime with acute lung diseases (n=24, average age 15 years, age range 5-47 years). Antibiotic therapy may not produce bacteriological eradication in such patients. There were no clinically significant changes in the pharmacokinetics of cefepime in patients with cystic fibrosis. Patients with impaired renal function In patients with varying degrees of renal insufficiency, T1/2 from the body increases, while there is a linear relationship between total clearance and creatinine clearance. With impaired renal function, dose adjustment is required. The average half-life in patients with severe renal impairment requiring dialysis is 13 hours with hemodialysis and 19 hours with continuous peritoneal dialysis. Patients with impaired liver function In patients with impaired liver function, when taking a single dose of cefepime 1 g, the pharmacokinetics did not change. Dose adjustment of the drug is not required in this group of patients. Elderly patients After a single intravenous administration of 1 g of cefepime to healthy volunteers over the age of 65, an increase in the area under the concentration-time curve (AUC) and a decrease in renal clearance compared to young subjects were observed. In elderly patients with impaired renal function, dose adjustment is recommended. Children The pharmacokinetics of cefepime was studied in children aged 2.1 months to 11.2 years after a single and repeated administration of a dose of 50 mg / kg of body weight intravenously or intramuscularly, as well as after repeated administration of cefepime (every 8 or 12 hours for at least 48 hours). After a single intravenous injection, the average values of total clearance and volume of distribution were 3.3 ml / min / kg and 0.3 l / kg, respectively. The half-life from the body averaged 1.7 hours. The excretion of cefepime unchanged by the kidneys averaged 60.4% of the administered dose, and renal clearance averaged 2.0 ml/min/kg. After repeated intravenous administration, the concentration of cefepime in the blood plasma in an equilibrium state did not differ from those after a single administration, except for a slight accumulation. Other pharmacokinetic parameters in infants and children did not differ with either single or multiple administration, as well as with different dosage regimens (8 or 12 hours). The age and gender of the patients did not significantly affect the pharmacokinetics of cefepime. After intramuscular administration, the maximum concentration of cefepime in the blood plasma at steady state averaged 68 mcg /ml and was achieved in an average of 0.75 hours. 8 hours after intramuscular administration, the minimum concentration of cefepime in the blood plasma at steady state averaged 6 micrograms /ml. The bioavailability of cefepime after intramuscular injection averaged 82%. Cefepime concentrations (± standard deviation) in cerebrospinal fluid (CSF) and in blood plasma and the ratio of concentrations in CSF/blood plasma in infants and children are shown in the table below*. Time after administration, hours N Plasma concentration, mcg/ml Concentration in CSF, mcg/ml Ratio of concentrations in CSF / blood plasma 0,5 7 67,1 (51,2) 5,7 (7,3) 0,12 (0,14) 1 4 44,1 (7,8) 4,3 (1,5) 0,10 (0,04) 2 5 23,9 (12,9) 3,6 (2,0) 0,17 (0,09) 4 5 11,7 (15,7) 4,2 (1,1) 0,87 (0,56) 8 5 4,9 (5,9) 3,3 (2,8) 1,02 (0,64) * The age of the patients ranged from 3.1 months to 12 years with a standard deviation 2.6 (3.0) years. In patients with suspected infections of the central nervous system, the dose of cefepime was 50 mg / kg of body weight with intravenous administration for 5-20 minutes every 8 hours. Plasma and CSF concentrations were determined at the end of administration on the 2nd or 3rd day of cefepime administration.
Indications for use Adults The drug is indicated for the treatment of the following infections in adults caused by microorganisms sensitive to cefepime: lower respiratory tract infections (including pneumonia and bronchitis); uncomplicated and complicated urinary tract infections (including pyelonephritis); skin and soft tissue infections; intraabdominal infections (including peritonitis and biliary tract infections); gynecological infections; bacteremia caused or suspected to be caused by any of the above infections; febrile neutropenia*; prevention of surgical infections during intraabdominal operations. Children ASTAPIM™ is intended for the treatment of the following infections caused by microorganisms sensitive to cefepime in children over the age of 2 months: pneumonia; uncomplicated and complicated urinary tract infections (including pyelonephritis); skin and soft tissue infections; septicemia; febrile neutropenia*; bacterial meningitis. * The drug is used as monotherapy for the empirical treatment of patients with febrile neutropenia. In patients with a high risk of developing severe infections (for example, with a recent bone marrow transplant, with arterial hypotension, with malignant blood diseases or severe or prolonged neutropenia), monotherapy with the drug may be insufficient. In such patients, complex antibacterial therapy is indicated. Empirical therapy with the drug can be initiated before receiving the results of a sensitivity study, followed by correction of the choice of antibiotic and treatment regimen, if necessary. ASTAPIM ™ can be used as monotherapy before the identification of the causative agent of infection, since the drug has a wide spectrum of antibacterial action against gram-positive and gram-negative microorganisms. In patients at risk of mixed aerobic and anaerobic infection, especially in the case of the possible presence of microorganisms insensitive to cefepime, it is recommended to start concomitant therapy with an anti-anaerobic drug before the identification of the pathogen. After identification of the pathogen and determination of sensitivity to cefepime, treatment should be carried out in accordance with the results of studies.
Method of administration and dosage The drug is intended for intravenous or intramuscular administration. The dose and route of administration depend on the severity of the infection, kidney function and the general condition of the patient. Method of application Intravenous administration The intravenous route of administration is used in patients with severe or life-threatening infections, especially at risk of septic shock. For intravenous injection, the powder of the drug is dissolved in one of the following solvents (see the table "Preparation of solution for intramuscular and intravenous administration" below): sterile water for injection; 5% glucose solution for injection; 0.9% sodium chloride solution for injection. The prepared solution of the drug is administered intravenously slowly for 3-5 minutes. For intravenous infusion, the prepared solution of the drug (see preparation above) is added to a vial containing a compatible infusion solution and administered for at least 30 minutes. The prepared solution of the drug in a concentration of 1-40 mg/ml is compatible with the following solutions: 0, 0.9% sodium chloride solution for injection; 5% or 10% glucose solution for injection; 1/6 M sodium lactate solution for injection; 5% glucose solution for injection and 0.9% sodium chloride solution for injection; Ringer's lactate solution for injection and 5% glucose solution for injection. The prepared solutions are stable for 24 hours at a temperature of 15 ° C-25 ° C or for 7 days when stored in the refrigerator (2 ° C-8 ° C). Intramuscular injection The powder of the drug is dissolved in one of the following solvents (for the volumes of added solvents, see the table "Preparation of solution for intramuscular and intravenous administration" below): sterile water for injection; 5% glucose solution for injection; 0.9% sodium chloride solution for injection; bacteriostatic water for injection with parabens or benzyl alcohol; 0.5% or 1.0% lidocaine hydrochloride solution for injection*. The prepared solutions are stable for 24 hours at a temperature of 15 ° C-25 ° C or for 7 days when stored in the refrigerator (2 ° C-8 ° C). The prepared solution of the drug is injected deep intramuscularly into a large muscle array (for example, into the outer upper quadrant of the gluteus maximus). A dose of up to 1 g can be administered as a single injection. The maximum dose of 2 g should be administered in the form of two injections in different places. * Since intramuscular injections of the drug are usually painless, in most cases there is no need to use lidocaine hydrochloride solution as a solvent. Table. Preparation of a solution for intramuscular and intravenous administration
Cefepime dosage/vial Volume of added solvent, ml Approximate volume obtained, ml Approximate concentration of cefepime, mg/ml Intravenously 1 g 10 11.4 90 Intramuscularly 1 g 3.0 4.4 230 The drug should not be mixed with other drugs in one syringe or in one infusion bottle. As with most beta-lactam antibiotics, ASTAPIM solution should not be added to a solution of metronidazole, vancomycin, gentamicin, tobramycin sulfate or netilmycin sulfate due to physical or chemical incompatibility. If concomitant therapy with cefepime is indicated, each of these drugs should be administered separately. Before the introduction of the prepared solution of the drug, it is necessary to make sure that the solution does not contain mechanical inclusions. Do not use the drug in the presence of foreign particles. From a microbiological point of view, the drug should be used immediately. If the preparation was not used immediately after preparation, the storage time and conditions should not exceed 24 hours at a temperature of 2 ° C-8 ° C in the case of preparation of the solution in uncontrolled and non-sterile conditions. As with other cephalosporins, the prepared solution of the drug may have a yellow-brown color, which does not affect the activity and quality of the drug. Dosage regimen Adults and children with a body weight of 40 kg with normal kidney function The recommended dosage regimen for adults and children with a body weight of 40 kg with normal kidney function* is presented in the table below: Type and severity of infection Dose and route of administration Interval between injections Urinary tract infections of mild to moderate severity 1.0 g intravenously or intramuscularly 12 hours Other infections of mild and moderate severity 1.0 g intravenously or intramuscularly 12 hours * The usual duration of therapy is 7-10 days, more severe infections may require longer treatment. For empirical treatment of febrile neutropenia, the usual duration of treatment is at least 7 days or until neutropenia resolves. Prevention of surgical infections during intraabdominal operations (adults) 60 minutes before the start of surgery, 2 g of the drug is administered intravenously in the form of an infusion lasting 30 minutes. Immediately after the end of the infusion, 0.5 g of metronidazole is administered intravenously to the patient. Due to the pharmaceutical incompatibility of metronidazole and cefepime, they should not be mixed in one vial of infusion solution. It is recommended to rinse the infusion system with a compatible liquid before administering metronidazole. During prolonged (more than 12 hours) surgical operations, the same dose of cefepime is re-administered 12 hours after the first dose of the drug, followed by metronidazole. Patients with impaired renal function In patients with impaired renal function, the dose of cefepime should be adjusted to compensate for the reduced rate of excretion of the drug by the kidneys. The recommended initial dose of cefepime in patients with mild to moderate renal impairment should be the same as in patients with normal renal function. Recommended maintenance doses for adult patients with impaired renal function are presented in the table below:
Creatinine clearance (ml/min) Recommended maintenance doses > 50 is the usual dose, no dose adjustment is required. 2 g each 8 hours 2 g each 12 hours 1 g each 12 hours 0.5 g every 12 hours 30-50 2 g every 12 hours 2 g each 24 hours 1 g every 24 hours 0.5 g every 24 hours 11-29 2 g each 24 hours 1 g every 24 hours 0.5 g every 24 hours 0.5 g every 24 hours ≤ 10 1 g each 24 hours 0.5 g every 24 hours 0.25g every 24 hours 0.25g every 24 hours Hemodialysis* 0.5 g every 24 hours 0.5 g every 24 hours 0.5 g every 24 hours 0.5 g every 24 hours * According to pharmacokinetic studies in patients undergoing hemodialysis, the dose of the drug should be reduced. In patients undergoing hemodialysis, the initial dose of the drug on the first day of therapy is 1 g, subsequently, the daily maintenance dose is 0.5 g for all infections, except febrile neutropenia, in which the daily maintenance dose is 1 g. On the day of hemodialysis, the drug is administered after the end of dialysis. If possible, the solution of the drug should be administered at the same time every day. If only the concentration of creatinine in the blood serum at equilibrium is known, creatinine clearance (SLcr) can be calculated using the following Cockcroft-Gault formulas:
Men:
SLcr (ml/min) =
Women: SLcr (ml/min) = SLcr (in men) × 0.85 Patients on dialysis During hemodialysis, about 68% of the administered dose of the drug is removed from the body within 3 hours. With continuous outpatient peritoneal dialysis, the drug can be used in doses recommended for patients with normal renal function, for example, 0.5 g, 1 g or 2 g, depending on the severity of the infection, with 48-hour intervals between injections. Patients with hepatic insufficiency Dose adjustment is not required. Children with normal kidney function (aged 2 months and older) Pneumonia, urinary tract infections, skin and soft tissue infections The usual recommended dose for children with a body weight of less than 40 kg is 50 mg/ kg every 12 hours for 10 days. In the case of more severe infections, the interval between injections can be reduced to 8 hours. Sepsis, bacterial meningitis and empirical treatment of febrile neutropenia The usual recommended dose for children with a body weight of less than 40 kg is 50 mg/ kg every 8 hours for 7-10 days. The experience of using cefepime in children under the age of 2 months is limited. Despite the clinical experience of using cefepime at a dose of 50 mg/ kg, the data of pharmacokinetic studies obtained in children older than 2 months show that in children aged A dose of cefepime 30 mg / kg every 12 or 8 hours can be used for 1-2 months. Doses of 50 mg / kg for patients older than 2 months and 30 mg / kg for patients aged 1-2 months are comparable to a dose of 2 g for adults. When using the drug, patients of this age group should be closely monitored. For children with a body weight of 40 kg, the dosage regimen is similar to that of adults. The dose for children should not exceed the maximum recommended dose for adults (2 g every 8 hours). The experience of intramuscular administration of cefepime in children is limited. Children with impaired renal function Since cefepim is mainly excreted by the kidneys, in children with impaired renal function, the dose of the drug should be adjusted by increasing the intervals between injections and / or reducing the dose in accordance with the recommended maintenance doses for adult patients with impaired renal function. According to the known concentration of creatinine in the blood serum , creatinine clearance is calculated using the following formulas:
SLcr (ml/min/1.73 m2) =
or
SLcr (ml/min/1.73 m2) =
Elderly patients In elderly patients, due to a more likely decrease in renal function, the dose should be selected with caution and renal function should be monitored. In patients with impaired renal function, dose adjustment is recommended.
Side effects When using other cephalosporins, the following adverse reactions have been reported: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxic neuropathy, aplastic anemia, hemolytic anemia, hemorrhage and false positive results for determining glucose levels in urine. Clinical studies In clinical studies of the use of cefepime (n = 5598), the most common adverse reactions were reactions from the gastrointestinal tract and hypersensitivity reactions. Frequency of occurrence: < 0.05% Hypersensitivity reactions: anaphylaxis. From the central nervous system: convulsions. Frequency of occurrence: 0.05-0.1% From the gastrointestinal tract: abdominal pain, constipation, candidiasis. From the central nervous system: dizziness, paresthesia, taste disorders. Other reactions: vasodilation, shortness of breath, genital itching, chills, inflammation at the injection site with intravenous infusion (0.1%). Frequency of occurrence: > 0.1-1% Hypersensitivity reactions: itching, urticaria. From the gastrointestinal tract: nausea, vomiting, candidiasis of the oral mucosa, colitis (including pseudomembranous colitis). From the central nervous system: headache. Other reactions: fever, vaginitis, erythema. Frequency of occurrence: > 1% Hypersensitivity reactions: rash (1.8%). From the gastrointestinal tract: diarrhea (1.2%). Other reactions: reactions at the injection site with intravenous infusion (5.2%), including phlebitis (2.9%), inflammation and pain at the site of intramuscular injection (2.6%). Post-marketing application experience The parameters of the frequency of adverse reactions are determined as follows: very often (≥ 1/10); often (≥ 1/100, but < 1/10); infrequently (≥ 1/1000, but < 1/100); rarely (≥ 1/10000, but < 1/1000); very rarely (< 1/10000); frequency unknown (cannot be estimated by available data). In each group, adverse reactions are presented in order of decreasing severity. Infectious and parasitic diseases: infrequently – candidiasis of the oral mucosa, vaginal infections; rarely - candidiasis. From the blood and lymphatic system: often – anemia, eosinophilia; infrequently – thrombocytopenia, leukopenia, neutropenia; frequency unknown – aplastic anemia, hemolytic anemia, agranulocytosis.From the immune system: rarely – anaphylactic reaction, angioedema; frequency unknown - anaphylactic shock. Mental disorders: the frequency is unknown – confusion, hallucinations. From the nervous system: infrequently – headache; rarely – convulsions, paresthesia, dysgeusia, dizziness; frequency unknown – coma, stupor, encephalopathy, altered state of consciousness, myoclonus. From the side of the vessels: often – phlebitis at the injection site; rarely – vasodilation; frequency unknown – hemorrhage. From the respiratory system, chest organs and mediastinum: rarely – dyspnea. From the gastrointestinal tract: often – diarrhea; infrequently – pseudomembranous colitis, colitis, nausea, vomiting; rarely - abdominal pain, constipation; frequency unknown – gastrointestinal disorders. From the skin and subcutaneous tissues: often – rash; infrequently – erythema, urticaria, itching; frequency unknown – toxic epidermal necrolysis*, Stevens-Johnson syndrome*, erythema multiforme*. From the kidneys and urinary tract: the frequency is unknown – impaired renal function, toxic nephropathy*. From the genitals and breast: the frequency is unknown – itching in the genital area. General disorders and disorders at the injection site: often – reactions at the infusion site, pain at the injection site, inflammation at the injection site; infrequently – pyrexia, inflammation at the infusion site; rarely – chills. Influence on the results of laboratory and instrumental studies: very often – a positive result of the Coombs test; often – an increase in the levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, an increase in bilirubin in the blood, an extension of prothrombin time, an extension of partial thromboplastin time; infrequently - an increase in the levels of urea in the blood, creatinine in the blood; frequency unknown – a false positive result of determining the level of glucose in the urine*. * Adverse reactions, usually related to other compounds of the cephalosporin group. Children The safety profile of cefepime in newborns and children is similar to that of adults. The most common adverse reaction reported in clinical studies was a rash. Reports of suspected adverse reactions Reports of suspected adverse reactions after drug registration are important. If a serious adverse reaction to a drug is detected in a patient or a new adverse reaction appears that is not described in this section, please inform in accordance with the National Pharmacovigilance System.
Contraindications Hypersensitivity to cefepime or any of the excipients, or to other cephalosporins or beta-lactam antibiotics (for example, penicillins, monobactams and carbapenems).
Drug interactions Interaction studies have not been conducted. When used simultaneously with anticoagulants, thrombolytics and antiplatelet agents, increased bleeding may occur. Probenecid slows down the excretion of cefepime by the kidneys, enhancing and prolonging its effect. In combination with alcohol intake, cefepime can cause an "antabuse, disulfiram-like" reaction with nausea and vomiting. The use of the drug can lead to false positive results of glucose determination in urine. In this regard, it is recommended to use enzyme tests with glucose oxidase to determine glucose in urine. Combined use with bacteriostatic antibacterial drugs may reduce the effectiveness of beta-lactam antibiotics.
Special instructions Hypersensitivity reactions As with other beta-lactam antibiotics, severe hypersensitivity reactions, including fatal cases, have been reported. Before starting treatment with the drug, patients should be carefully examined for possible hypersensitivity reactions in the anamnesis to cefepime, beta-lactams or other medications. The drug should be used with caution in patients with a history of asthma or prone to allergies. At the beginning of treatment, the patient should be closely monitored. If an allergic reaction to cefepime occurs, the use of the drug should be stopped immediately and appropriate therapy should be prescribed. Severe hypersensitivity reactions may require the use of adrenaline and additional maintenance therapy. Antibacterial activity of cefepime Before using the drug, identification and determination of the sensitivity of the pathogen to cefepime should be carried out. Impaired renal function In patients with impaired renal function (creatinine clearance is < 50 ml / min) or with other conditions that cause impaired renal function, the dose of the drug should be adjusted to compensate for the reduced rate of excretion of the drug by the kidneys. Since in patients with impaired renal function or other factors affecting renal function, when using the usual dosage regimen, the level of cefepime may be high and persist for a long time, the maintenance dose should be reduced. When determining the optimal dosage regimen, the degree of renal dysfunction, the severity of infection and the sensitivity of the microorganisms that caused the infection should be taken into account. During the post-marketing experience with cefepime, the following severe adverse reactions were observed: reversible encephalopathy (disorders of consciousness, including confusion, hallucinations, stupor and coma), myoclonia, convulsions (including non-convulsive epileptic status) and / or renal failure. Most cases were observed in patients with impaired renal function when using cefepime at doses exceeding the recommended ones. In general, neurotoxic symptoms were reversible and resolved after discontinuation of cefepime and/or after hemodialysis. In some cases, deaths have been reported. Diarrhea associated with Clostridium difficile Almost all broad-spectrum antibacterial drugs, including cefepime, can cause diarrhea associated with Clostridium difficile (CDAD), which can range from mild diarrhea to fatal colitis. Thus, it is important to consider this diagnosis in patients with diarrhea that occurs after the use of antibacterial agents. Patients should be closely monitored for the development of CDAD, as cases of its occurrence were observed two months after antibacterial therapy. If CDAD is suspected or confirmed, the use of antibiotics other than those prescribed to suppress Clostridium difficile should be discontinued. Superinfection The use of the drug may cause the growth of insensitive microorganisms. With the development of superinfection, appropriate measures should be taken. It is necessary to carefully monitor kidney function while using drugs with potential nephrotoxic effects, such as aminoglycosides or potent diuretics, with ASTAPIM. Elderly patients In clinical studies involving more than 6,400 adult patients (35% aged over 65 years and 16% aged 75 years and older) when using the usual recommended dose for adults, the clinical efficacy and safety of cefepime were comparable to those in adult patients with normal renal function, not related to the elderly and senile age. There was a slight increase in the half-life and a decrease in renal clearance compared to younger subjects. In patients with impaired renal function, dose adjustment is recommended. Since cefepime is mainly excreted by the kidneys, there is an increased risk of toxic reactions in patients with impaired renal function. In elderly patients, due to a more likely decrease in renal function, the dose should be selected with caution and renal function should be monitored. Severe adverse reactions have been observed in elderly patients with renal insufficiency with conventional doses of cefepime, such as reversible encephalopathy (disorders of consciousness, including confusion, hallucinations, stupor and coma), myoclonia, seizures (including non-convulsive epileptic status) and/or renal failure. Influence on the results of laboratory tests In patients receiving cefepim twice a day, false positive results of the Coombs test without hemolysis were observed. As with the use of other cephalosporins, false positive results of glucosuric tests performed using methods based on copper reduction (using Benedict's solution, Fehling's solution or Clinitest tablets) may be noted during treatment with the drug. In this regard, it is recommended to use enzyme tests with glucose oxidase to determine glucose in urine. Fertility, use during pregnancy and lactation Fertility In studies on rats, no deterioration in fertility was observed. There is no data on the effect of cefepime on human fertility. The potential risk to humans is unknown. Pregnancy Adequate and well-controlled studies in pregnant women have not been conducted. In reproductive studies on mice, rats and rabbits, no direct or indirect effect on fetal development was found. There are insufficient preclinical studies of the effect of cefepime on fertility and fetal development, childbirth and postnatal development. Therefore, the drug is recommended for use during pregnancy only if absolutely necessary, and if the therapeutic benefit exceeds the potential risk. Lactation Cefepime is excreted in breast milk in a small amount. The drug should be used with caution during breastfeeding and only when the potential benefit to the mother exceeds the possible risk to the child. Influence on the ability to drive vehicles and manage mechanisms Studies on the effect on the ability to drive vehicles and control mechanisms have not been conducted. However, when using cefepime, undesirable reactions may occur (such as altered state of consciousness, dizziness, confusion or hallucinations), affecting the ability to drive vehicles and control mechanisms.
Overdose In case of overdose, in cases of significant excess of the recommended doses, especially in patients with impaired renal function, hemodialysis is performed to remove cefepime from the body. Peritoneal dialysis is ineffective. Accidental overdose was observed when using high doses of cefepime in patients with impaired renal function. Symptoms of overdose: encephalopathy (disorders of consciousness, including confusion, hallucinations, stupor, coma), myoclonia, convulsions.
Release form Powder for the preparation of an injection solution, in a glass bottle, closed with a rubber stopper, a corrugated aluminum cap and closed with a safety plastic lid. One bottle is packed together with the instructions for medical use. Storage conditions Store in a dry place protected from light, at a temperature not exceeding 25 ° C. Keep out of reach of children.
Expiration date 3 years. Do not use after the expiration date.
Conditions of release from pharmacies By prescription.
The owner of the registration certificate "M.R. Healthcare Pvt. Ltd." Vill. Tanda Mallu, Kashipur Road, Ramnagar, Distt. Nainital, Uttarakhand-244715, India.
Name and address of the organization accepting claims (proposals) on the quality of medicines in the territory of the Republic of Uzbekistan LLC "Astanova Healthcare" Tashkent, Yakkasaraysky district, Yakkasaroy str., house-5. Tel.: (+998) 71 253 22 37, (+998) 71 253 22 57. Sot.: (+998) 97 265 55 71.
