SAVIM [Cefepime] 1 g Powder for solution for I\V, I\V administration
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instructions
for the medical use of the medicinal product
SAVIM
Tradename
Savim, Савим
International non-proprietary name or generic name
Cefepime, Цефепим
Dosage form
Powder for the preparation of solution for intravenous and intramuscular
administration.
Composition per 1 bottle
active
substance: cefepime hydrochloride monohydrate equiv. cefepime 1 g;
excipients: L-arginine.
Composition for 1 bufus solvent
Water for injection 5 ml.
An antibiotic of the cephalosporin group.
АТХ Code: J01DE01
Pharmacodynamics
Cefepime
is an antibacterial agent from the group of fourth-generation cephalosporins.
It has a bactericidal effect, disrupting the synthesis of the cell wall of
microorganisms. It has a broad spectrum of action against gram-positive and
gram-negative bacteria, strains resistant to aminoglycosides and / or
third-generation cephalosporin antibiotics. It is highly resistant to
hydrolysis of most beta-lactamases and quickly penetrates gram-negative
bacterial cells. Inside the bacterial cell, the molecular target is
penicillin-binding proteins. It is active in vivo and in vitro against
gram-positive aerobes: Staphylococcus aureus (only methicillin-sensitive
strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A),
Streptococcus viridans group; gram-negative aerobes: Enterobacter spp.,
Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas
aeruginosa.
In
vitro active (but clinical significance unknown) against gram-positive aerobes:
Staphylococcus epidermidis (methicillin-sensitive strains only), Staphylococcus
saprophyticus, Streptococcus agalactiae (group B); Gram-negative aerobes:
Acinetobacter lwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter
agglomerans, Haemophilus influenzae (including beta-lactamase-producing
strains), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including
beta-lactamase-producing strains), Morganella morganii, Proteus vulgaris, Providencia
rettgeri, Providencia stuartii, Serratia marcescens.
Most
strains of Enterococcus spp., including Enterococcus faecalis,
methicillin-resistant staphylococci, Stenotrophomonas maltophilia (formerly
known as Xanthomonas maltophilia and Pseudomonas maltophilia), Clostridium
difficile are not sensitive to cefepime.
Bioavailability is 100%. The time to reach the maximum concentration
after intravenous and intramuscular administration at a dose of 0.5 g is by the
end of the infusion 1-2 hours, respectively. The maximum concentration with
intramuscular administration at doses of 0.5, 1 and 2 g is 14, 30 and 57 mcg /
ml, respectively; with intravenous administration at doses of 0.25, 0.5, 1 and
2 g - 18, 39, 82 and 164 mcg / ml, respectively; the time to reach the average
therapeutic concentration in plasma is 12 hours; the average therapeutic
concentration with intramuscular administration is 0.2 mcg / ml, with
intravenous administration - 0.7 mcg / ml. High concentrations are determined in
urine, bile, peritoneal fluid, blister exudate, bronchial mucus, sputum,
prostate gland, appendix and gall bladder. Distribution volume is 0.25 l/kg, in
children from 2 months to 16 years - 0.33 l/kg. Plasma protein binding is 20%.
Metabolized in the liver and kidneys by 15%. The half-life is 2 hours, total
clearance is 120 ml/min, renal clearance is 110 ml/min. Excreted by the kidneys
(by glomerular filtration unchanged - 85%), with breast milk. The half-life
with hemodialysis is 13 hours, with continuous peritoneal dialysis - 19 hours.
Indications
for use
Infectious and inflammatory diseases caused by microorganisms sensitive
to cefepime: pneumonia (moderate and severe) caused by Streptococcus pneumoniae
(including cases of association with concomitant bacteremia), Pseudomonas
aeruginosa, Klebsiella pneumoniae or Enterobacter spp.; Febrile neutropenia
(empirical 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, Enterobacter spp.
Hypersensitivity to cefepime, components of the drug, other
cephalosporins, penicillins, other beta-lactam antibiotics, children under 2
months (for intravenous administration), children under 12 years (for
intramuscular administration), breastfeeding period.
Method
of administration and dosage
Intravenous infusion (for at least 30 minutes) or intramuscular (only
for complicated or uncomplicated urinary tract infections of mild to moderate
severity caused by Escherichia coli).
Pneumonia (moderate to severe) caused by Streptococcus
pneumoniae (including cases associated with concomitant bacteremia),
Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.:
intravenously 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 resolves.
Complicated or
uncomplicated urinary tract infections of mild to moderate severity caused by Escherichia
coli, Klebsiella pneumoniae, Proteus mirabilis: intravenously or
intramuscularly (only for infections caused by Escherichia coli) 0.5-1 g every
12 hours for 7-10 days.
Severe complicated or
uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia
coli or Klebsiella pneumoniae: intravenously 2 g every 12 hours for 10 days.
Moderate to severe skin
and soft tissue infections caused
by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus
pyogenes: intravenously 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.: intravenously 2 g every
12 hours for 7-10 days.
For children aged 2 months to 16 years and weighing up to 40 kg, the
recommended dosage regimen for all indications (excluding febrile neutropenia)
is 50 mg/kg every 12 hours intravenously; for febrile neutropenia - 50 mg/kg
every 8 hours. The duration of treatment is the same as for adults. In chronic
renal failure, the dose is prescribed depending on the severity of the
infection and creatinine clearance (CC): more than 60 ml / min - 0.5-1-2 g
every 12 hours or 2 g every 8 hours, with CC 30 - 60 ml / min - 0.5-1-2 g every
24 hours or 2 g every 12 hours, with CC 11 - 29 ml / min - 0.5-1-2 g every 24
hours, less than 11 ml / min - 0.25-0.5-1 g every 24 hours; continuous
ambulatory peritoneal dialysis - 0.5-1-2 g every 48 hours. Patients on
hemodialysis are administered 1 g on the 1st day, then 0.5 g every 24 hours for
all infections and 1 g every 24 hours 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 administer the drug 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 similarity of
pharmacokinetics in children and adults, the dosing regimen (reducing the dose
or increasing the interval between administrations) in children with chronic
renal failure is similar to the dosing regimen in adults.
Preparation of injection
solutions
To prepare a solution for intravenous administration, the drug
(1.0 g) is dissolved in 10 ml of sterile water for injection, 5% dextrose
solution or 0.9% sodium chloride solution. 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 at least 30 minutes.
To prepare a solution for intramuscular administration, the drug
(1.0 g) is dissolved in 2.4 ml of sterile water for injection, 0.9% sodium
chloride solution, 0.5% or 1% lidocaine hydrochloride solution.
Special
instructions and precautions
Before using the drug, consult a doctor. If
pseudomembranous colitis with prolonged diarrhea occurs, stop taking the drug
and prescribe vancomycin (orally) or metronidazole. Cross-hypersensitivity is
possible in patients with allergic reactions to penicillins. In case of
combined severe renal and hepatic insufficiency, the drug concentration in
plasma should be regularly determined (the dose is adjusted depending on
creatinine clearance). With long-term treatment, regular monitoring of
peripheral blood, liver and kidney function is necessary. In case of mixed
aerobic-anaerobic infection, until the pathogens are identified, a combination
with drugs active against anaerobes is advisable. Patients in whom meningeal
dissemination occurs from a remote site of infection, meningitis is suspected
or the diagnosis of meningitis is confirmed, should be prescribed an
alternative antibiotic with confirmed clinical efficacy for this situation. It
is possible to detect a false positive Coombs test, a false positive test for
glucose in urine.
Use with caution in: gastrointestinal diseases (including history),
especially colitis, regional enteritis or antibiotic-associated colitis, severe
chronic renal failure.
Influence on the ability to drive vehicles and mechanisms
During the treatment period, it is necessary to refrain from driving
vehicles and engaging in potentially dangerous activities that require
increased concentration and speed of psychomotor reactions.
Use during pregnancy and
breastfeeding
The
use of the drug during pregnancy is possible only in cases where the potential
benefit to the mother outweighs the risk to the fetus. If it is necessary to
prescribe the drug during lactation, breastfeeding should be suspended.
Allergic reactions: skin rash (including
erythematous eruptions), itching, fever, anaphylactoid reactions, anaphylactic
shock, false-positive Coombs test, eosinophilia, erythema multiforme exudative
(including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's
syndrome).
From the nervous system: headache, dizziness,
insomnia, paresthesia, anxiety, confusion, convulsions, encephalopathy.
From the genitourinary
system: vaginitis.
From the urinary system: renal dysfunction.
From the digestive system: diarrhea, nausea, vomiting,
constipation, abdominal pain, dyspepsia, pseudomembranous colitis. From the
hematopoietic system: anemia, thrombocytopenia, leukopenia, neutropenia,
pancytopenia, hemolytic anemia, bleeding, increased prothrombin time or partial
thromboplastin time.
From the respiratory system: cough.
From the cardiovascular
system: tachycardia, dyspnea, peripheral edema.
Laboratory parameters: decreased hematocrit,
increased prothrombin time, increased urea concentration, hypercreatininemia,
hypercalcemia, increased activity of "liver" transaminases and
alkaline phosphatase, hyperbilirubinemia.
Local reactions: with intravenous
administration - phlebitis, with intramuscular administration - hyperemia and
pain at the injection site.
Others: sore throat, chest pain,
taste changes, increased sweating, back pain, asthenia, development of
superinfection, oropharyngeal candidiasis.
If any of the side effects
listed in the instructions worsen, or you notice any other side effects not
listed in the instructions, tell your doctor.
Interaction with other medicinal
products
Pharmaceutically
incompatible with other antimicrobial drugs and heparin. Diuretics reduce
tubular secretion of cefepime and increase its concentration in the blood
serum, prolong the half-life, increase nephrotoxicity (increases the risk of
nephronecrosis). Nonsteroidal anti-inflammatory drugs, slowing the excretion of
cephalosporins, increase the risk of bleeding. Incompatible with metronidazole
solution (before administering metronidazole solution to prevent infections
during surgical interventions, the infusion system should be flushed from
cefepime solution). Increases nephro- and ototoxicity of aminoglycosides.
Symptoms (more common in patients with chronic renal failure): convulsions,
encephalopathy, neuromuscular excitation.
Treatment: symptomatic therapy and hemodialysis.
Store in a dark place at a
temperature not exceeding 30°C. Keep out of reach of children.
Do not use after expiration date.
Dispensed by prescription.
1 bottle with powder for solution preparation and 2 bufuses with solvent together with instructions for use in a cardboard box.