Active substanceCefepimCefepim
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  • Dosage form: & nbspPowder for the preparation of solution for intravenous and intramuscular injection.
    Composition:
    active substance: cefepime hydrochloride monohydrate (in terms of cefepime) - 0.5 g, 1 g.
    auxiliary substance: arginine.
    Description:
    The powder is white or white with a yellowish hue of color, hygroscopic.

    Pharmacotherapeutic group:Antibiotic-cephalosporin.
    ATX: & nbsp

    J.01.D.E.01   Cefepim

    Pharmacodynamics:
    Antibacterial agent from the group of cephalosporins of the IV generation. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. Has a wide spectrum of action against Gram-positive and Gram-negative bacteria, strains resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation.It is highly resistant to hydrolysis of most beta-lactamases and rapidly penetrates into gram-negative bacterial cells. Inside the bacterial cell, the molecular target is penicillin-binding proteins.
    It is active in vivo and in vitro for gram positive aerobes: Staphylococcus aureus (only methicill and insensitive strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A), Streptococcus viridans; Gram-negative aerobes: Enterobacter spp., Escherichia coli. Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa. In vitro is active against gram-positive aerobes: Staphylococcus epidermidis (only methicillin-sensitive strains), Staphylococcus saprophytics, Streptococcus agalactiae (group B); Gram-negative aerobes: Acinetobacter Kvoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including strains producing beta-lactamase), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhal is (including strains producing beta-lactamases), Morganella morganii , Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marccscens. Most strains of Enterococcus, incl. Enterococcus faecalis, methicillin-resistant staphylococci, Stenotrophomonas maltophilia (formerly known as Xanthomonas maltophilia), Clostridium difficile are not sensitive to cefepime.
    Pharmacokinetics:
    Bioavailability of 100%. Time to reach the maximum concentration (TCmax) after intravenous (intravenous) and intramuscular (IM) administration at a dose of 0.5 g - by the end of infusion and 1 -2 hours, respectively. The maximum concentration (steel) with the / m introduction in doses of 0.5. 1 and 2 g - 14, 30 and 57 μg / ml, respectively; with iv introduction in doses of 0.25, 0.5, 1 and 2 g - 18, 39,82 and 164 μg / ml, respectively; time to reach the average therapeutic concentration in plasma - 12 h; The average therapeutic concentration at the m / v introduction is -0.2 μg / ml. at the time of / in - 0.7 mcg / ml. High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucus secretion, sputum, prostate gland, appendix and gallbladder. The volume of distribution - 0.25 l / kg, in children from 2 months to 16 years - 0.33 l / kg. Connection with plasma proteins - 20%.
    Metabolized in the liver and kidneys by 15%. The half-life (T1 / 2) is 2 hours, the total clearance is 120 ml / min, the renal clearance is 110 ml / min. It is excreted by the kidneys (by glomerular filtration in unchanged form - 85%), with breast milk. T1 / 2 -13 hr hemodialysis, continuous peritoneal dialysis at -19 h.
    Indications:
    Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:
    Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .. Febrile neutropenia (empiric therapy).
    Complicated and uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis.
    Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes.
    Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli. Klebsiella pneumoniae. Pseudomonas aeruginosa, Entcrobactcr spp. Bacteroides fragilis.
    Prevention of infections in the conduct of cavitary surgery.
    Contraindications:Hypersensitivity to the components that make up the drug (including antibiotics for cephalosporins, penicillins and other beta-lactam antibiotics); Children under 2 months of age (for intravenous administration) (safety and efficacy in children younger than 2 months not established); Children under 12 years of age (for intramuscular route of administration).
    Carefully:Diseases of the gastrointestinal fact (including in the anamnesis): pseudomembranous colitis, ulcerative colitis, regional enteritis or antibiotic-associated colitis; chronic renal failure.
    Pregnancy and lactation:When pregnancy is used only if the intended benefit for the mother exceeds the potential risk to the fetus. During treatment with the drug during lactation, breastfeeding should be discontinued.
    Dosing and Administration:

    Intravenous (intravenously), intramuscularly (in / m) (only with complicated or uncomplicated urinary tract infections of mild and moderate severity caused by E. coli). Doses and the route of administration of the drug vary depending on the sensitivity of the microorganisms of the pathogens, the severity of the infection, as well as the state of kidney function in the patient.

    Pneumonia (moderate to severe), caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia). Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.: in / in 1-2 g every 12 hours for 10 days.

    Febrile neutropenia (empirical therapy): iv 2 g every 8 hours for 7 days or until neutropenia is resolved.

    Complicated or uncomplicated urinary tract infections nymeth light and medium severity caused by Escherichia coli. Klebsiella pneumoniae. Proteus mirabilis: in / in or / m (only for infections caused by Escherichia coli) for 0.5-1 g every 12 h "for 7-10 days.

    Severe complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae: in / in 2 g every 12 hours for 10 days.

    Moderately severe and severe infections of the skin and soft tissues, caused by Staphylococcus aureus (only methicillin-sensitive strains). Streptococcus pyogenes: in / in 2 g every 2 hours for 10 days.

    Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides frangilis: in / in 2 g every 12 hours for 7-10 days.

    To prevent infection during surgical interventions on the abdominal organs: 60 minutes prior to the beginning of the surgical operation, 2 g of the drug is administered intravenously for 30 minutes. At the end of the infusion, add an additional 500 mg of metronidazole intravenously. Metronidazole solutions should not be administered concomitantly with cefepime. Infusion system before the introduction of metronidazole should be washed. During long (more than 12 hours) surgical operations 12 hours after the first dose, it is recommended to re-administer 2 g of the drug intravenously for 30 minutes, followed by the administration of 500 mg of metronidazole.

    In children from 2 months to 16 years of age and with a body weight of up to 40 kg, the recommended dosing regimen for all indications (excluding febrile neutropenia) is 50 mg / kg every 12 hours IV; with febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment as in adults (7-10 days).

    In patients with impaired renal function (creatinine clearance <30 ml / min), the dose of the drug should be adjusted. The initial dose of cefepime should be the same as for patients with normal renal function. Recommended maintenance dosespreparation are presented in the table.

    Clearance

    creatinine

    (ml / min)

    Recommended maintenance doses

    >50

    2 g every 8 h (normal dose, no adjustment required)

    2 g every 12 hours (normal dose, no adjustment needed)

    1 g every 12 h (normal dose, no adjustment required)

    500 mg every 12 hours (normal dose, no adjustment required)

    30-50

    2 g every 8 hours

    2 g every 12 h

    1 g every 12 h

    500 mg every

    12 h

    11-29

    1 g every 12 h

    i g every 24 hours

    500 mg every 24 hours

    500 mg every 24 hours

    <10

    1 g every 24 h

    500 mg every 24 hours

    250 mg every 24 hours

    250 mg every 24 hours

    Patients on hemodialysis on day 1 are given 1 g, then 0.5 g every 24 h for all infections and 1 g every 24 h for the treatment of febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is desirable to enter cefepime every day at the same time.

    Data on the use of the drug in children with concomitant chronic renal insufficiency are not available, however, given the similar pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between administrations) in children with chronic renal failure is similar to the dosing regimen in adults.

    To prepare a solution for intravenous administration, the preparation is dissolved in 5 ml (0.5 g) or 10 ml (1.0 g) of sterile water forinjections. 5% dextrose solution or 0.9% solution of sodium chloride. Intravenously injected intravenously for 3-5 minutes. For intravenous infusion, the prepared solution is combined with other solutions for intravenous infusions (0.9% sodium chloride solution, 5% or 10% dextrose solution, Ringer's solution with lactate and 5% dextrose solution, maximum concentration 40 mg / ml) and administered for not less than 30 minutes.

    To prepare a solution for intravenous administration, the preparation is dissolved in sterile water for injection, 0.9% solution of sodium chloride, bacteriostatic water for injection with paraben or benzyl alcohol, in 0.5% and 1% solution of lidocaine hydrochloride (0.5 g in 1.3 ml, 1.0 g in 2.4 ml).

    Side effects:

    Allergic reactions: skin rash (including erythematous rashes), itching, fever, anaphylactoid reactions, eosinophilia, multiforme exudative erythema (including Stevens-Johnson syndrome), rarely - toxic epidermal nscrolisis (Lyell's syndrome).

    From the nervous system: headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions, encephalopathy (in the absence of dose adjustment in patients with impaired renal function).

    From the genitourinary system: vaginitis.

    From the urinary system: impaired renal function.

    From the gastrointestinal tract: diarrhea, nausea, vomiting, constipation or diarrhea, pain in the abdomen, dyspepsia, pseudo-cerebral colitis.

    On the part of the organs of hematopoiesis: anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, hemolytic anemia, bleeding.

    From the respiratory system: cough, chest pain.

    From the cardiovascular system: tachycardia, dyspnea, peripheral edema. Laboratory indicators: decreased hematocrit, increased prothrombin time, increased urea concentration, hypercreatininaemia, gyercalcaemia, increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, Coombs positive test (without hemolysis).

    Local Reactions: with intravenous injection - phlebitis, with intramuscular injection - hyperemia and soreness at the injection site.

    Other: pain in the throat, thoracology, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.

    Overdose:Symptoms (often occur in patients with chronic renal failure): convulsions, encephalopathy, neuromuscular excitation. Treatment: hemodialysis and maintenance therapy.
    Interaction:
    Pharmaceutically incompatible with other antimicrobial drugs and heparin.
    Diuretics, aminoglycosides, polymyxin B reduce the tubular secretion of cefepime and increase its serum concentration, extend T1 / 2, increase nephrotoxicity (increases the risk of nephroncrosis). Cefepim increases the ototoxicity of aminoglycosides.
    Nonsteroidal anti-inflammatory drugs, slowing the excretion of cephalosporins, increase the risk of bleeding. With the simultaneous administration of bactericidal antibiotics (aminoglycosides), synergism appears with bacteriostatic (macrolides. chloramphenicol, tetracyclines) - antagonism. Incompatible with the solution of metronidazole (before the administration of the solution of metronidazole for the prevention of infections during surgical interventions, the infusion system should be rinsed from the solution of cefepime). To avoid possible drug interactions with other drugs, cefepime solutions (as well as most other beta-lactam antibiotics) should not be administered concomitantly with solutions of vancomycin, gentamicin, tobramycin, netilmicin.When prescribing cefepime with the listed drugs, each antibiotic should be administered separately.
    Special instructions:
    When using cefepime, pseudomembranous colitis may occur. Therefore, it is important to bear this diagnosis in case of diarrhea during treatment with the drug. Light forms of colitis do not require special treatment, it is enough to stop the introduction of the drug; mild or severe cases may require special treatment.
    There is a possibility of cross-over hypersensitivity in patients with allergic reactions to penicillins.
    When combined severe renal and hepatic insufficiency should regularly determine the concentration of the drug in the plasma (dose adjustment is performed depending on the creatinine clearance).
    With prolonged treatment, regular monitoring of peripheral blood, indicators of the functional state of the liver and kidneys is necessary.
    With mixed aerobic-anaerobic infection, the combination with drugs active against anaerobes is appropriate before identification of pathogens. Patients who have a meningeal dissemination from a distant foci of infection, suspicions of meningitis or a diagnosis of meningitis are confirmed,an alternative antibiotic should be prescribed with clinical efficacy confirmed for the given situation.
    It is possible to detect a positive Coombs test, a false-positive glucose test in the urine.
    Form release / dosage:
    Powder for the preparation of solution for intravenous and intramuscular injection 0.5 g, 1 g.


    Packaging:
    For 0.5 g or 1 g of active substance in bottles of colorless clear glass with a capacity of 10 ml or 20 ml.
    For 1, 5 or 10 bottles with instructions for use in a pack of cardboard.
    For 50 bottles with an equal number of instructions for use in cardboard boxes (for hospitals).
    Solvent:
    - "Water for injection" in glass ampoules of 5 ml;
    or
    - "Sodium chloride solvent for the preparation of medicinal forms for injection 0.9%" in glass ampoules of 5 ml.
    1 bottle with the drug, 1 or 2 ampoules with a solvent in the contoured cell packs from a polyvinyl chloride film. 1 contour pack with instructions for use and ampoule ampoule in a pack of cardboard.
    1 vial, 1 or 2 with a solvent ampoule, with instructions for use and a lancet ampulnam bundle or box made of cardboard.5 bottles of the drug in a contour cell pack from a polyvinyl chloride film. 1, 2 contour mesh packages with vials of the preparation and instructions for use in a pack of cardboard. 1 contour mesh package with vials of the preparation, 1 or 2 contour mesh packages with solvent ampoules (5 ampoules each), instructions for use and ampoule ampoule in a pack of cardboard.
    When using ampoules with a kink ring or with a notch and a dot, the scarifier is not inserted.
    Storage conditions:In dry, the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.
    Shelf life:2 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-009403/09
    Date of registration:23.11.2009
    The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp21.10.2015
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