Cefepime - instructions for use, dose, side effects, contraindications

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 methicillin-susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A), Streptococcus group of viridans;

Gram-negative aerobes: Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.

In vitro is active (but not clinically important) for gram-positive aerobes: Staphylococcus epidermidis (methicillin-susceptible strains only), Staphylococcus saprophytics, Streptococcus agalactiae (group B);

Gram-negative aerobes: Acinetobacter Iwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including strains producing beta-lactamase), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including strains producing beta-lactamases), 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.

Pharmacokinetics:Bioavailability is 100%. Time to reach the maximum concentration after intravenous and intramuscular injection at a dose of 0.5 g - by the end of the infusion, 1-2 hours, respectively. The maximum concentration for intramuscular injection in doses of 0.5, 1 and 2 g is 14, 30 and 57 μg / ml, respectively; when administered intravenously at 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 hours; the average therapeutic concentration for intramuscular injection is 0.2 μg / ml, with intravenous administration of 0.7 μg / 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 is 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 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. Half-life with hemodialysis - 13 hours, with continuous peritoneal dialysis - 19 hours.

Indications:

Infectious-inflammatory diseases caused by susceptible to cefepime microorganisms: 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.

Contraindications:Hypersensitivity to cefepime, the components of the drug, other cephalosporins, penicillins, other beta-lactam antibiotics, children under 2 months of age (for intravenous administration), children under 12 years of age (for intramuscular injection), lactation.

Carefully:Diseases of the gastrointestinal tract (including in the anamnesis), especially colitis, regional enteritis or antibiotic-associated colitis, severe chronic renal failure.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in cases where the potential benefit to the mother exceeds the risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenous infusion (for at least 30 minutes) or intramuscularly (only with complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli).

Pneumonia (medium and heavy) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.; intravenously 1-2 g every 12 hours for 10 days.

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

Complicated or uncomplicated urinary tract infections of mild and moderate severitycaused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis: intravenously or intramuscularly (only for infections caused by Escherichia coli) for 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.

Severe and severe skin and soft tissue infectionscaused by Staphylococcus aureus (only methicillin-sensitive strains), 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.

In children from 2 months to 16 years 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 intravenously; with febrile neutropenia - 50 mg / kg every 8 hours.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 - 0.5-1-2 g every 12 hours or 2 g every 8 hours, with QC 30-60 ml / min - 0.5-1-2 g every 24 hours or 2 g every 12 hours, with a CK of 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; permanent ambulatory peritoneal dialysis - 0.5-1-2 g every 48 hours. Patients on hemodialysis on day 1 are given 1 g, 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 enter cefepime every day at the same time. The data on the drug administration in children with chronic renal failure attendant is not available, however, considering the similarity of pharmacokinetics in children and in adults, dosing regimen (dose reduction or increase in the interval between doses) in children with chronic renal failure similar to the adult dosage regime.

Preparation of injection solutions

To prepare a solution for intravenous administration, the preparation (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 injected for not less than 30 minutes.

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

Side effects:

Allergic reactions: skin rash (including erythematous rashes), itching, fever, anaphylactoid reactions, anaphylactic shock, false-positive Coombs test, eosinophilia, multiforme exudative erythema (including Stevens-Joison syndrome), toxic epidermal necrolysis (Lyell's syndrome).

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

From the nervous system: headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions, encephalopathy.

From the genitourinary system: Vaginitis.

From the urinary system: impaired renal function.

From the digestive system: diarrhea, nausea, vomiting, constipation, abdominal pain,

dyspepsia, pseudomembranous colitis.

On the part of the organs of hematopoiesis: 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 indicators: a decrease in hematocrit, an increase in prothrombin time, an increase in urea concentration, hypercreatininaemia, hypercalcemia, an increase in the activity of "hepatic" transaminases and alkaline phosphatase, and hyperbilirubinemia.

Other: pain in the throat, chest pain, change in taste, 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 symptomatic therapy.

Interaction:

Pharmaceutically incompatible with other antimicrobial drugs and heparin.

Diuretics reduce the tubular secretion of cefepime and increase its concentration in the blood serum, prolong the half-life, increase the nephrotoxicity (increased risk of nefronekroza).

Nonsteroidal anti-inflammatory drugs, slowing the excretion of cephalosporins, increase the risk of bleeding.

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.

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 identifying pathogens, a combination with drugs active against anaerobes is appropriate. Patients who have a meningeal dissemination from a distant foci of infection, suspected meningitis or a diagnosis of meningitis have been confirmed, an alternative antibiotic with confirmed clinical efficacy should be prescribed.

It is possible to detect a false positive sample of Coombs, a false positive test for glucose in the urine.

Effect on the ability to drive transp. cf. and fur:During the period of treatment it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1.0 g.

Packaging:

By 1.0 g of active substance into 10 ml vials, hermetically sealed with stoppers made of rubber compound, crimped with aluminum caps or caps combined.

Vials with a drug of 10, 14, 25, 50 pieces are placed in boxes of cardboard with an equal number of instructions for the use of the drug (for hospitals).

1 bottle with the drug and instructions for use are placed in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002441

Date of registration:29.12.2011

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp20.10.2015

Illustrated instructions

Instructions

Cefepim (Cefepime)