Composition, form of production and packaging
Powder for preparation of a solution for iv and in / m introduction white or white with a yellowish shade of color.
1 f.
cefepime hydrochloride 500 mg
Excipients: arginine 0.365 g.
Solvent: water d / and (5 ml).
1 g - Glass bottles with a capacity of 10 ml (1) - packs of cardboard.
1 g - Glass bottles with a capacity of 10 ml (1) complete with a solvent (1 pc.) - packings of cellular contour (1) - packs of cardboard.
1 g - Glass bottles with a capacity of 10 ml (5) - packings of cellular contour (1) - packs cardboard.
1 g - Vials with a capacity of 10 ml (5) complete with a solvent (amp 5 pcs.) - packings of cellular contour (1) - packs of cardboard.
Powder for preparation of a solution for iv and in / m introduction white or white with a yellowish shade of color.
1 f.
cefepime hydrochloride 1 g
Excipients: arginine 0.73 g.
Solvent: water d / and (5 ml).
1 g - Glass bottles with a capacity of 10 ml (1) - packs of cardboard.
1 g - Glass bottles with a capacity of 10 ml (1) complete with a solvent (1 pc.) - packings of cellular contour (1) - packs of cardboard.
1 g - Glass bottles with a capacity of 10 ml (5) - packings of cellular contour (1) - packs cardboard.
1 g - Vials with a capacity of 10 ml (5) complete with a solvent (amp 5 pcs.) - packings of cellular contour (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Antibiotic from the group of cephalosporins of IV generation. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms, (inactivates the enzyme transpeptidase). Rapidly penetrates the membrane of gram-negative bacteria; has a high affinity for penicillin-binding proteins or bacterial transpeptidases.
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. Highly resistant to hydrolysis of most beta-lactamases. Maksicef В® is active against the following microorganisms: Gram-positive aerobes : Staphylococcus aureus and Staphylococcus epidermidis (only methicillin-sensitive strains), Staphylococcus hominis, Staphylococcus saprophyticus, other strains of Staphylococcus spp .; Streptococcus pyogenes (serogroup A); Streptococcus agalactiae (serogroup B); Streptococcus pneumoniae, incl. strains of pneumococci resistant to penicillin; and other beta-hemolytic Streptococcus spp. (serogroup C, G, F), Streptococcus bovis (serogroup D), Streptococcus viridans; Gram-negative aerobes: Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; Gram-negative aerobes: Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas stutzeri); Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae); Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans and Enterobacter sakazakii); Proteus spp.(including Proteus mirabilis and Proteus vulgaris); Acinetobacter calcoaceticus (Acinetobacter anitratum, Acinetobacter calcoaceticus subsp. Bvoff); Aeromonas hydrophila; Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii); Campylobacter
jejuni, Campylobacter vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including strains producing beta-lactamase); Haemophilus parainjluenzae, Hafnia alvei, Legionella spp .; Morganella morganii; Moraxella catarrhalis (including strains producing beta-lactamases); Neisseria gonorrhoeae (including strains producing beta-lactamases); Neisseria meningitidis, Providencia spp. (including Providencia rettgeri, Providencia Stuartii); Salmonella spp .; Serratia spp. (including Serratia marcescens, Serratia liquefaciens); Shigella spp .; Yersinia enterocolitica; anaerobes: Clostridium perfringens; Fusobacterium spp .; Mobil uncus spp .;Peptostreptococcus spp .; Veillonella spp., Propionibacterium spp.
PHARMACOKINETICS
Bioavailability of 100%. The time to reach C max after intravenous and / m administration at a dose of 0.5 g - by the end of infusion and after 1-2 hours, respectively.With max at the / m introduction in doses of 0.5 g and 1 g - 14 mcg / ml and 30 mcg / ml, respectively; with intravenous administration in doses of 0.5 g and 1 g - 39 Ојg / ml and 82 Ојg / ml, respectively; time to reach the average therapeutic concentration in plasma -12 hours; the average therapeutic concentration at the IM injection is 0.2 Ојg / ml, with an IV of -0.7 Ојg / ml. High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucus secretion, sputum, prostate gland, appendix and gallbladder. V d - 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%. T 1/2 -2 h, total clearance - 120 ml / min, renal clearance -110 ml / min. It is excreted by the kidneys (by glomerular filtration in unchanged form - 85%), with breast milk. T 1/2 for hemodialysis - 13 hours, with continuous peritoneal dialysis-19 hours.
INDICATIONS
Bacterial infections caused by susceptible microorganisms:
- pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .;
- febrile neutropenia (empirical therapy);
- complicated and uncomplicated infections
urinary tract (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, Enterobacter spp., Bacteroides fragilis;
- prevention of postoperative infection.
DOSING MODE
Adults and adolescents over 16 years of age or children with a body weight of more than 40 kg: IV infusion (for at least 30 minutes) or IM (only with complicated or uncomplicated mild and moderate urinary tract infections caused by E. coli) .
Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .: 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 mild and moderate urinary tract infections caused by E. coli, Klebsiella pneumoniae, Proteus mirabilis : iv or IM (for E. coli infections only), 0.5-1 g every 12 hours for 7 -10 days.
Severe complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by E. coli or Klebsiella pneumoniae : iv 2 g every 12 hours for 10 days.
Severe and severe skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes : iv 2 g every 12 hours for 10 days.
Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella
pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis : iv 2 g every 12 hours for 7-10 days.
Children from 2 months to 16 years of age or with a body weight of up to 40 kg - the recommended dosing regimen for all indications (excluding febrile neutropenia) - 50 mg / kg every 12 hours IV; with febrile neutropenia - 50 mg / kg every 8 hours. The maximum single dose should not exceed 2 g. Duration of treatment - as in adults.
In chronic renal failure, the dose is prescribed depending on the severity of the infection and the clearance of creatinine (CC): more than 60 ml / min - 0.5 g, 1 g or 2 g every 12 hours or 2 g every 8 hours, KK 30-60 ml / 0.5 g, 1 g or 2 g every 24 h or 2 g every 12 h, with a KK of 11-29 ml / min - 0.5 g, 1 g or 2 g every 24 h, less than 11 ml / min - 0.25 g, 0.5 g or 1 g every 24 hours; permanent ambulatory peritoneal dialysis - 0.5 g 1 g or 2 g every 48 h. 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 treatment febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is advisable to inject cefepime every day at the same time.
Data on the use of the drug in children with concomitant chronic renal failure 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 is similar to the dosing regimen in adults.
For IV administration, dissolve in sterile water for injection, 5% dextrose solution or 0.9% solution of sodium chloride; for the / m introduction - in sterile water for injection with paraben or benzyl alcohol, in 0.5 and 1% solution of lidocaine.
SIDE EFFECT
Maxi cefВ® is usually well tolerated. Undesirable drug reactions are rare and transient.
Allergic reactions: skin rash (including erythematous rashes), itching, fever, anaphylactoid reactions, Coombs positive reaction, eosinophilia, multiforme exudative erythema (including Stevens-Johnson syndrome), rarely - toxic epidermal necrolysis (syndrome Lyell).
Local reactions: with iv introduction - phlebitis, with / m - hyperemia and soreness at the site of administration.
From the nervous system: headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions.
From the genitourinary system: vaginitis.
From the side of the urinary system: a violation of kidney function.
From the digestive system: diarrhea, nausea, vomiting, constipation, abdominal pain, indigestion, pseudomembranous enterocolitis.
On the part of the organs of hematopoiesis: anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, hemolytic anemia, bleeding.
From the respiratory system: cough.
From the cardiovascular system: tachycardia, dyspnea, peripheral edema.
Laboratory indicators: a decrease in hematocrit, an increase in prothrombin time, an increase in the concentration
urea, hypercreatininaemia, hypercalcemia, increased activity of hepatic transaminases and AF, hyperbilirubinemia.
Other: sore throat, thoracalgia, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.
CONTRAINDICATIONS
- immediate type hypersensitivity to cefepime, L-arginine (including other cephalosporins, penicillins, other beta-lactam antibiotics);
- Children's age (up to 2 months).
With caution: pregnancy, lactation, gastrointestinal diseases (including in the anamnesis), especially colitis, severe chronic renal failure
PREGNANCY AND LACTATION
Use with caution in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in severe chronic renal failure.
APPLICATION FOR CHILDREN
Children from 2 months to 16 years of age or with a body weight of up to 40 kg - the recommended dosing regimen for all indications (excluding febrile neutropenia) - 50 mg / kg every 12 hours IV; with febrile neutropenia - 50 mg / kg every 8 hours. The maximum single dose should not exceed 2 g. Duration of treatment as in adults.
The drug is contraindicated for children under 2 months.
SPECIAL INSTRUCTIONS
If pseudomembranous colitis occurs with prolonged diarrhea, stop taking and prescribe vancomycin (inside) or metronidazole.
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 a mixed aerobic-anaerobic infection before identification of pathogens, a combination with a drug active against anaerobes is appropriate.
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 with confirmed clinical efficacy should be prescribed.
It is possible to detect a positive Coombs test, a false positive test for glucose in the urine.
The prepared solution should not be stored for more than 24 hours at room temperature or for 7 days in a refrigerator. The color change does not affect the activity of the drug.
OVERDOSE
Symptoms (often occur in patients with chronic renal failure): convulsions, encephalopathy, neuromuscular excitation.
Treatment: symptomatic and supportive therapy; hemodialysis.
DRUG INTERACTION
Pharmaceutically incompatible with other antimicrobial drugs and heparin.
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).
Increases the nephro- and ototoxicity of aminoglycosides.
Powerful diuretics (including furosemide) - the risk of nephrotoxic action of cefepime.
NSAIDs, slowing the excretion of cephalosporins, increase the risk of bleeding.
With simultaneous administration with aminoglycosides, a pronounced synergism of the antimicrobial effect is observed.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. In a dry, the dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life - 2 years. Do not use after the expiration date.
